Details of the Researcher

PHOTO

Shunji Sugawara
Section
Graduate School of Dentistry
Job title
Specially Appointed Professor(Research)
Degree

  • 歯学博士（東北大学）

Education 2

  • Tohoku University　Graduate School, Division of Dental Research　歯学基礎系

    - 1988/03

  • Tohoku University　Faculty of Dentistry

    - 1984/03

Committee Memberships 2

  • 歯科基礎医学会　評議員

    2003/05 - Present

  • 日本細菌学会　評議員

    2006/01 - 2009/12

Research Interests 5

  • immune tolerance

  • salivary gland

  • host defence

  • mucosal immunity

  • oral mucosa

Research Areas 3

  • Life sciences / Oral medicine / Oral Anatomy and Morphological Basic Dentistry

  • Life sciences / Immunology /

  • Life sciences / Bacteriology /

Awards 1

  1. JAOB/Lion Dental Research Award

    2004/09/24　歯科基礎医学会　口腔粘膜の生体防御機構と口腔粘膜シグナル伝達病に関する研究

Papers 149

  1. Neutrophil extracellular traps inhibit osteoclastogenesis. International-journal

    Kento Numazaki, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Kenji Matsushita, Itaru Mizoguchi, Shunji Sugawara

    Biochemical and biophysical research communications　705　149743-149743　2024/02/29

    DOI： 10.1016/j.bbrc.2024.149743 　

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    Neutrophil extracellular traps (NETs) released by neutrophils upon inflammation or infection, act as an innate immune defense against pathogens. NETs also influence inflammatory responses and cell differentiation in host cells. Osteoclasts, which are derived from myeloid stem cells, are critical for the bone remodeling by destroying bone. In the present study, we explores the impact of NETs, induced by the inflammatory agent calcium ionophore A23187, on the differentiation and activation of osteoclasts, potentially through suppressing RANK expression. Our results collectively suggested that the inhibition of RANKL-mediated osteoclastogenesis by NETs might lead to the suppression of excessive bone resorption during inflammation.

  2. 好中球細胞外トラップはRANKの発現を抑制し破骨細胞分化を負に制御する

    沼崎 研人, 多田 浩之, 菅原 俊二, 溝口 到

    日本矯正歯科学会大会プログラム・抄録集　82回　183-183　2023/11

    Publisher: (公社)日本矯正歯科学会

  3. Macrophage migration inhibitory factor-mediated mast cell extracellular traps induce inflammatory responses upon Fusobacterium nucleatum infection Peer-reviewed

    Hiroyuki Tada, Takashi Nishioka, Rina Ishiyama, Li-Ting Song, Sakura Onoue, Kazuyoshi Kawahara, Eiji Nemoto, Kenji Matsushita, Shunji Sugawara

    <B>Biochemical and Biophysical Research Communications<B>, in press　2023/06

    DOI： 10.1016/j.bbrc.2023.06.060 　

  4. カルシポトリオールは制御性T細胞を介してマウス遅延型過敏症に対する舌下免疫療法を増強する

    黒石 智誠, Reiska Kumala Bakti, 坂東 加南, 菅原 俊二

    ビタミン　97　(4)　224-224　2023/04

    Publisher: (公社)日本ビタミン学会

    ISSN： 0006-386X

  5. IL-33 induces histidine decarboxylase, especially in c-kit+ cells and mast cells, and roles of histamine include negative regulation of IL-33-induced eosinophilia

    Kanan Bando, Yukinori Tanaka, Saka Winias, Shunji Sugawara, Itaru Mizoguchi, Yasuo Endo

    Inflammation Research　2023/02/01

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s00011-023-01699-y 　

    ISSN： 1023-3830

    eISSN： 1420-908X

  6. &lt;i&gt;N&lt;/i&gt;-acetyl cysteine inhibits IL-1α release from murine keratinocytes induced by 2-hydroxyethyl methacrylate

    Takahiro Kaji, Toshinobu Kuroishi, Kanan Bando, Masatoshi Takahashi, Shunji Sugawara

    The Journal of Toxicological Sciences　48　(10)　557-569　2023

    Publisher: Japanese Society of Toxicology

    DOI： 10.2131/jts.48.557 　

    ISSN： 0388-1350

    eISSN： 1880-3989

  7. Lipopolysaccharide Priming Exacerbates Anaphylatoxin C5a-Induced Anaphylaxis in Mice.

    Makoto Yasuda, Yukinori Tanaka, Kanan Bando, Shunji Sugawara, Kentaro Mizuta

    Biological & pharmaceutical bulletin　46　(3)　432-439　2023

    DOI： 10.1248/bpb.b22-00766 　

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    Anaphylaxis is a serious allergic or hypersensitivity reaction with a sudden onset that can be life-threatening or fatal. Previous studies have highlighted two pathways of anaphylaxis in mice. One is the classical immunoglobulin E (IgE)-mediated pathway that involves mast cells and histamine. The other is an alternative IgG-mediated pathway that involves basophils, monocytes/macrophages, neutrophils, and the platelet-activating factor (PAF). However, little is known about the mechanism by which complement anaphylatoxins contribute to the induction of anaphylaxis. Infection is a cofactor that potentially amplifies the risk of anaphylaxis. Here, we showed that priming with a lipopolysaccharide (LPS), which mimics bacterial infection, exacerbates anaphylatoxin C5a-induced anaphylaxis in mice. LPS plus C5a-induced anaphylaxis was mediated by histamine and lipid mediators, especially PAF. Cell depletion experiments demonstrated that LPS plus C5a-induced anaphylaxis depended on monocytes/macrophages, basophils, and neutrophils. These results suggest that C5a is a potent inducer of anaphylaxis in bacterial infections. Remarkably, the molecular and cellular mediators of LPS plus C5a-induced anaphylaxis are mostly shared with IgE- and IgG-mediated anaphylaxis. Therefore, combined inhibition of histamine and PAF may be beneficial as a second-line treatment for severe anaphylaxis.

  8. Hericium erinaceus ethanol extract and ergosterol exert anti-inflammatory activities by neutralizing lipopolysaccharide-induced pro-inflammatory cytokine production in human monocytes

    Hiroyuki Tada, Kazuyoshi Kawahara, Hiraku Osawa, Li-Ting Song, Kento Numazaki, Junya Kawai, Sakura Onoue, Takashi Nishioka, Eiji Nemoto, Kenji Matsushita, Shunji Sugawara

    Biochemical and Biophysical Research Communications　636　1-9　2022/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2022.10.090 　

    ISSN： 0006-291X

  9. Differential expression of CD11c defines two types of tissue-resident macrophages with different origins in steady-state salivary glands

    Lu Lu, Toshinobu Kuroishi, Yukinori Tanaka, Mutsumi Furukawa, Tomonori Nochi, Shunji Sugawara

    Scientific Reports　12　(1)　2022/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-022-04941-5 　

    eISSN： 2045-2322

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    <title>Abstract</title>Gland macrophages are primed for gland development and functions through interactions within their niche. However, the phenotype, ontogeny, and function of steady-state salivary gland (SG) macrophages remain unclear. We herein identified CD11c+ and CD11c− subsets among CD64+ macrophages in steady-state murine SGs. CD11c− macrophages were predominant in the SGs of embryonic and newborn mice and decreased with advancing age. CD11c+ macrophages were rarely detected in the embryonic period, but rapidly expanded after birth. CD11c+, but not CD11c−, macrophage numbers decreased in mice treated with a CCR2 antagonist, suggesting that CD11c+ macrophages accumulate from bone marrow-derived progenitors in a CCR2-dependent manner, whereas CD11c− macrophages were derived from embryonic progenitors in SGs. CD11c+ and CD11c− macrophages strongly expressed colony-stimulating factor (CSF)-1 receptor, the injection of an anti-CSF-1 receptor blocking antibody markedly reduced both subsets, and SGs strongly expressed CSF-1, indicating the dependency of SG resident macrophage development on CSF-1. The phagocytic activity of SG macrophages was extremely weak; however, the gene expression profile of SG macrophages indicated that SG macrophages regulate gland development and functions in SGs. These results suggest that SG CD11c+ and CD11c− macrophages are developed and instructed to perform SG-specific functions in steady-state SGs.

  10. Histamine acts via H4-receptor stimulation to cause augmented inflammation when lipopolysaccharide is co-administered with a nitrogen-containing bisphosphonate

    Kanan Bando, Yukinori Tanaka, Tetsu Takahashi, Shunji Sugawara, Itaru Mizoguchi, Yasuo Endo

    Inflammation Research　2022/10/29

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s00011-022-01650-7 　

    ISSN： 1023-3830

    eISSN： 1420-908X

  11. Neutrophil extracellular trapsによるRANKL誘導性破骨細胞の分化制御(The functional role of neutrophil extracellular traps in RANKL-induced osteoclastogenesis)

    沼崎 研人, 多田 浩之, 松下 健二, 溝口 到, 菅原 俊二

    Journal of Oral Biosciences Supplement　2022　103-103　2022/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  12. Neutrophil extracellular trapsによるRANKL誘導性破骨細胞の分化制御(The functional role of neutrophil extracellular traps in RANKL-induced osteoclastogenesis)

    沼崎 研人, 多田 浩之, 松下 健二, 溝口 到, 菅原 俊二

    Journal of Oral Biosciences Supplement　2022　162-162　2022/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  13. Porphyromonas gingivalis線毛はLPSによるヒト単球のインターロイキン-6産生を相乗的に誘導する(Synergistic effect of Porphyromonas gingivalis fimbriae on the lipopolysaccharide-induced production of interleukin-6 in human monocytic cells)

    遠山 学, 多田 浩之, 沼崎 研人, 松下 健二, 菅原 俊二

    Journal of Oral Biosciences Supplement　2022　385-385　2022/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  14. Reactivation of p53 by RITA Induces Apoptosis in Human Oral Squamous Cell Carcinoma Cells. International-journal

    Manabu Endo, Takashi Nishioka, Kento Numazaki, Hiroshi Hasegawa, Tetsu Takahashi, Shunji Sugawara, Hiroyuki Tada

    Anticancer research　42　(6)　2931-2937　2022/06

    DOI： 10.21873/anticanres.15775 　

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    BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is one of the most common tumors of the head and neck region. The tumor suppressor gene p53 (TP53) is the most frequently mutated gene in OSCC and TP53 mutations are associated with decreased survival and resistance to chemotherapy in patients with OSCC. Therefore, therapeutic strategies targeting TP53 reactivation are required to effectively treat OSCC. In this study, we investigated the effect of various p53-reactivating small molecules (RITA, PRIMA-1, and CP-31398) on the proliferation of human OSCC cell lines (Ca9-22, HSC-2, HSC-3, and HSC-4) derived from human oral tissues bearing a mutant TP53 gene. MATERIALS AND METHODS: Apoptosis induction by RITA was assessed by measuring Annexin V and propidium iodide (PI)-positive cells using flow cytometry. p53 and murine double minute 2 (MDM2) phosphorylation and Bax expression were detected in the lysates of RITA-treated Ca9-22 cells using western blotting. RESULTS: RITA markedly inhibited the growth of Ca9-22, HSC-2, HSC-3, and HSC-4 cells. In Ca9-22 cells, RITA induced apoptosis and inhibited cell proliferation while increasing p53 phosphorylation and Bax expression; however, RITA did not induce MDM2 phosphorylation. CONCLUSION: The inhibitory effect of RITA on human OSCC cell proliferation is mediated by apoptosis induction through p53 and Bax.

  15. Porphyromonas gingivalis Gingipains-Mediated Degradation of Plasminogen Activator Inhibitor-1 Leads to Delayed Wound Healing Responses in Human Endothelial Cells. International-journal

    Li-Ting Song, Hiroyuki Tada, Takashi Nishioka, Eiji Nemoto, Takahisa Imamura, Jan Potempa, Chang-Yi Li, Kenji Matsushita, Shunji Sugawara

    Journal of innate immunity　1-14　2021/11/25

    DOI： 10.1159/000519737 　

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    Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is constitutively produced by endothelial cells and plays a vital role in maintaining vascular homeostasis. Chronic periodontitis is an inflammatory disease characterized by bleeding of periodontal tissues that support the tooth. In this study, we aimed to determine the role of PAI-1 produced by endothelial cells in response to infections caused by the primary periodontal pathogen Porphyromonas gingivalis. We demonstrated that P. gingivalis infection resulted in significantly reduced PAI-1 levels in human endothelial cells. This reduction in PAI-1 levels could be attributed to the proteolysis of PAI-1 by P. gingivalis proteinases, especially lysine-specific gingipain-K (Kgp). We demonstrated the roles of these degradative enzymes in the endothelial cells using a Kgp-specific inhibitor and P. gingivalis gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by P. gingivalis induced a delayed wound healing response in endothelial cell layers via the low-density lipoprotein receptor-related protein. Our results collectively suggested that the proteolysis of PAI-1 in endothelial cells by gingipains of P. gingivalis might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier.

  16. レジンモノマー2-Hydroxyethyl methacrylateはマウスケラチノサイトからのIL-1α放出を誘導する

    梶 恭大, 黒石 智誠, 坂東 加南, 高橋 正敏, 菅原 俊二

    日本歯科医師会雑誌　74　(4)　478-478　2021/07

    Publisher: (公社)日本歯科医師会

    ISSN： 0047-1763

  17. Nitrogen-containing Bisphosphonates and Lipopolysaccharide Mutually Augment Inflammation via ATP- and IL-1β-mediated Production of NETs. International-journal

    Kanan Bando, Toshinobu Kuroishi, Hiroyuki Tada, Takefumi Oizumi, Yukinori Tanaka, Tetsu Takahashi, Itaru Mizoguchi, Shunji Sugawara, Yasuo Endo

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research　36　(9)　1866-1878　2021/06/02

    DOI： 10.1002/jbmr.4384 　

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    Among the bisphosphonates (BPs), nitrogen-containing BPs (N-BPs) have much stronger anti-bone-resorptive actions than non-N-BPs. However, N-BPs have various side-effects such as acute influenza-like reactions after their initial administration and osteonecrosis of the jawbones after repeated administration. The mechanisms underlying such effects remain unclear. To overcome these problems, it is important to profile the inflammatory nature of N-BPs. Here, we analyzed the inflammatory reactions induced in mouse ear-pinnas by the N-BPs alendronate (Ale) and zoledronate (Zol). We found the following. (i) Ale and Zol each induced two phases of inflammation (early weak and late strong ear-swelling). (ii) Both phases were augmented by lipopolysaccharides [LPS; cell-surface constituent of gram-negative bacteria (including oral bacteria)], but prevented by inhibitors of the phosphate transporters SLC20/34. (iii) Macrophages and neutrophils were involved in both phases of Ale+LPS-induced ear-swelling. (iv) Ale increased or tended to increase various cytokines, and LPS augmented these effects, especially that on IL-1β. (v) ATP was involved in both phases, and Ale alone or Ale+LPS increased ATP in ear-pinnas. (vi) The augmented late-phase swelling induced by Ale+LPS depended on both IL-1 and neutrophil extracellular traps (NETs, neutrophil-derived net-like complexes). (vii) Neutrophils, together with macrophages and dendritic cells, also functioned as IL-1β-producing cells, and upon stimulation with IL-1β, neutrophils produced NETs. (viii) Stimulation of P2X7 receptors by ATP induced IL-1β in ear-pinnas. (ix) NET formation by Ale+LPS was confirmed in gingiva, too. These results suggest that (1) N-BPs induce both early- and late-phase inflammation via ATP-production and P2X7-receptor stimulation, (2) N-BPs and LPS induce mutually augmenting responses both early and late phases via ATP-mediated IL-1β production by neutrophils, macrophages, and/or dendritic cells, and (3) NET production by IL-1β-stimulated neutrophils may mediate the late phase, leading to prolonged inflammation. These results are discussed in relation to the side effects seen in patients treated with N-BPs. This article is protected by copyright. All rights reserved.

  18. P2 purinergic receptor signaling and interleukin-1 synergistically induce interleukin-6 production in a human oral squamous carcinoma cell line. International-journal

    Kaori Shishido, Toshinobu Kuroishi, Shunji Sugawara

    Journal of oral biosciences　63　(1)　80-90　2021/03

    DOI： 10.1016/j.job.2021.01.004 　

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    OBJECTIVES: The aim of this study was to investigate the inflammatory roles of P2 purinergic receptor (P2R) signaling in oral squamous cell carcinoma (OSCC). METHODS: Human OSCC cell lines HSC-2, Ca9-22, and HO-1-u-1 were stimulated with P2R agonists. The concentration of interleukin (IL)-6 in culture supernatants was measured using an enzyme-linked immune sorbent assay. Expression levels of messenger RNAs (mRNAs) were analyzed using reverse transcription polymerase chain reaction. Phosphorylation of intracellular signaling molecules was analyzed using western blotting. RESULTS: HSC-2 cells expressed the mRNAs for P2X4-6 and all P2YRs. ATP or ADP induced significantly greater production of IL-6 by HSC-2 cells. Ca9-22 cells expressed mRNAs for P2X4-6 and all P2YRs except P2Y4. ATP or ADP induced the production of IL-6 by Ca9-22 cells, but the IL-6 concentration was much lower than that in HSC-2 cells. Although HO-1-u-1 cells expressed the mRNAs for P2X4-6 and all P2YRs, ATP or ADP did not induce IL-6 production. The production of IL-6 by HSC-2 cells stimulated with adenine nucleotides was significantly inhibited by P2R antagonists and a p38 mitogen-activated protein kinase inhibitor, but not by extracellular signal-related kinase or c-Jun N-terminal kinase inhibitors. The proinflammatory cytokine IL-1 significantly augmented P2R-induced IL-6 production by HSC-2 cells via the nuclear factor-κB signaling pathway. CONCLUSIONS: The present study suggests that P2Rs signaling and IL-1 synergistically induce chronic inflammation in OSCC. Because chronic inflammation is a well-known driving force of tumor progression, these results support therapeutic strategies that target P2Rs signaling in OSCC.

  19. Release of Nitrogen-Containing Bisphosphonates (NBPs) from Hydroxyapatite by Non-NBPs and by Pyrophosphate.

    Kanan Bando, Takefumi Oizumi, Tetsu Takahashi, Itaru Mizoguchi, Shunji Sugawara, Yasuo Endo

    Biological & pharmaceutical bulletin　44　(11)　1670-1680　2021

    DOI： 10.1248/bpb.b21-00320 　

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    Bisphosphonates (BPs) are major anti-bone-resorptive drugs. Among them, the nitrogen-containing BPs (NBPs) exhibit much stronger anti-bone-resorptive activities than non-nitrogen-containing BPs (non-NBPs). However, BP-related osteonecrosis of the jaw (BRONJ) has been increasing without effective strategies for its prevention or treatment. The release of NBPs (but not non-NBPs) from NBP-accumulated jawbones has been supposed to cause BRONJ, even though non-NBPs (such as etidronate (Eti) and clodronate (Clo)) are given at very high doses because of their low anti-bone-resorptive activities. Our murine experiments have demonstrated that NBPs cause inflammation/necrosis at the injection site, and that Eti and Clo can reduce or prevent the inflammatory/necrotic effects of NBPs by inhibiting their entry into soft-tissue cells. In addition, our preliminary clinical studies suggest that Eti may be useful for treating BRONJ. Notably, Eti, when administered together with an NBP, reduces the latter's anti-bone-resorptive effect. Here, on the basis of the above background, we examined and compared in vitro interactions of NBPs, non-NBPs, and related substances with hydroxyapatite (HA), and obtained the following results. (i) NBPs bind rapidly to HA under pH-neutral conditions. (ii) At high concentrations, Eti and Clo inhibit NBP-binding to HA and rapidly expel HA-bound NBPs (potency Eti>>Clo). (iii) Pyrophosphate also inhibits NBP-binding to HA and expels HA-bound NBPs. Based on these results and those reported previously, we discuss (i) possible anti-BRONJ strategies involving the use of Eti and/or Clo to reduce jawbone-accumulated NBPs, and (ii) a possible involvement of pyrophosphate-mediated release of NBPs as a cause of BRONJ.

  20. Migratory dendritic cells in skin-draining lymph nodes have nickel-binding capabilities International-journal Peer-reviewed

    Toshinobu KUROISHI, Kanan BANDO, Reiska Kumala BAKTI, Gaku OUCHI, Yukinori TANAKA, Shunji SUGAWARA

    Scientific Reports　10　(1)　5050-5050　2020/03

    DOI： 10.1038/s41598-020-61875-6 　

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    Nickel (Ni) is the most frequent metal allergen and induces Th1-dependent type-IV allergies. In local skin, epidermal Langerhans cells (LCs) and/or dermal dendritic cells (DCs) uptake antigens and migrate to draining lymph nodes (LNs). However, the subsets of antigen-presenting cells that contribute to Ni presentation have not yet been identified. In this study, we analyzed the Ni-binding capabilities of murine DCs using fluorescent metal indicator Newport Green. Elicitation of Ni allergy was assessed after intradermal (i.d.) injection of Ni-treated DCs into ear pinnae of Ni-sensitized mice. The Ni-binding capabilities of MHC class IIhi CD11cint migratory DCs were significantly stronger than those of MHC class IIint CD11chi resident DCs and CD11cint PDCA1+ MHC class IIint B220+ plasmacytoid DCs. Migratory DCs in skin-draining and mandibular LNs showed significantly stronger Ni-binding capabilities than those in mesenteric and medial iliac LNs. An i.d. injection of IL-1β induced the activation of LCs and dermal DCs with strong Ni-binding capabilities. Ni-binding LCs were detected in draining LNs after i.d. challenge with IL-1β and Ni. Moreover, an i.d. injection of Ni-treated DCs purified from skin-draining LNs elicited Ni-allergic inflammation. These results demonstrated that migratory DCs in skin-draining LNs have strong Ni-binding capabilities and elicit Ni allergy.

  21. Metabolomic analysis of liver from dietary biotin deficient mice Peer-reviewed

    Toshinobu Kuroishi, Shunji Sugawara

    Journal of Nutritional Science and Vitaminology　66　(1)　82-85　2020

    DOI： 10.3177/jnsv.66.82 　

    ISSN： 0301-4800

    eISSN： 1881-7742

  22. ゾレドロネート静脈内投与マウスでのLPSによるIL-1αおよびIL-1βの増加に関してのクロドロネートによる抑制

    鈴木 飛佳理, 坂東 加南, 木山 朋美, 大泉 丈史, 多田 浩之, 遠藤 康男, 菅原 俊二, 高橋 哲

    日本口腔科学会雑誌　68　(2)　147-147　2019/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  23. Mechanisms underlying the induction of regulatory T cells by sublingual immunotherapy. International-journal Peer-reviewed

    Yukinori Tanaka, Satoshi Fukumoto, Shunji Sugawara

    Journal of oral biosciences　61　(2)　73-77　2019/06

    DOI： 10.1016/j.job.2019.02.001 　

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    BACKGROUND: Sublingual immunotherapy (SLIT) is used for the treatment of type 1 allergies, such as allergic rhinitis. SLIT leads to tolerance against allergens possibly via the redirection of allergen-specific T helper 2 cells to T helper 1 cells and the generation of peripheral regulatory T (Treg) cells. However, the detailed mechanisms remain unclear. Systemic tolerance to orally administered antigens (oral tolerance) has been extensively investigated. Recent studies have recognized the central role of Treg cells and classical dendritic cells (cDCs) in oral tolerance development. HIGHLIGHT: This review focuses on recent advances in the understanding of the underlying mechanisms of SLIT compared with those of oral tolerance. The sublingual administration of soluble protein antigens has been reported to induce antigen-specific Treg cells in oral mucosa-draining submandibular lymph nodes in mice. The generation of Treg cells is critical for SLIT efficacy because the transfer of SLIT-induced Treg cells confers tolerance against the antigens. A large number of oral cDCs with the CD103-CD11b+ phenotype exert retinoic acid-producing activity and convert naïve CD4+ T cells into Foxp3+ Treg cells in vitro in a transforming growth factor-β-dependent and retinoic acid-dependent manner. Oral CD103-CD11b+ cDCs transport sublingual antigens to submandibular lymph nodes and induce antigen-specific Treg cells. Sublingual antigens enter the mucosa most likely by crossing the sublingual ductal epithelium and are captured by oral antigen-presenting cells, especially macrophages. CONCLUSION: Oral CD103-CD11b+ cDCs are specialized for the induction of Treg cells in mice; thus, targeting their human counterpart may enhance the therapeutic effects of SLIT.

  24. Interleukin-1 and histamine are essential for inducing nickel allergy in mice. International-journal Peer-reviewed

    Kanan Bando, Toshinobu Kuroishi, Shunji Sugawara, Yasuo Endo

    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology　49　(10)　1362-1373　2019

    DOI： 10.1111/cea.13467 　

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    BACKGROUND: We previously reported that (a) lipopolysaccharide (LPS) is a potent adjuvant for inducing Nickel (Ni) allergy in mice at both the sensitization and elicitation steps, (b) LPS induces Interleukin-1 (IL-1) and histidine decarboxylase (HDC, the histamine-forming enzyme), and IL-1 induces HDC, (c) Ni allergy is induced in mast cell-deficient, but not IL-1-deficient (IL-1-KO) or HDC-KO mice. OBJECTIVE: To examine the roles of IL-1 and HDC (or histamine) and their interrelationship during the establishment of Ni allergy. METHODS: Ni (NiCl2 ) 1 mmol/L containing IL-1β and/or histamine was injected intraperitoneally (sensitization step). Ten days later, test substance(s) were intradermally injected into ear pinnas (elicitation step), and ear swelling was measured. RESULTS: In wild-type mice, Ni + LPS or Ni + IL-1β injection at sensitization step followed by Ni alone at elicitation step induced Ni allergy. In IL-1-KO, injection of Ni + IL-1β (but not Ni + histamine) was required at both sensitization and elicitation steps to induce Ni allergy. In HDC-KO, Ni + IL-1β + histamine at sensitization step followed by Ni + histamine at elicitation step induced Ni allergy. In histamine H1 receptor-deficient mice, IL-1β induced HDC, but was ineffective as an adjuvant for inducing Ni allergy. In wild-type mice, injection into ear pinnas of Ni 10 mmol/L alone or Ni 1 mmol/L + LPS induced IL-1β, HDC and a prolonged swelling of ear pinnas. In non-sensitized mice, injection of IL-1β by itself into ear pinnas in IL-1-KO mice induced prolonged ear swelling. Ni augmented IL-1 production (both IL-1α and IL-1β) and HDC induction in wild-type mice sensitized to Ni. CONCLUSIONS: In mice: (a) for inducing Ni allergy, IL-1 is essential at both the sensitization and elicitation steps, and HDC induction is involved in the effect of IL-1, (b) stimulation of H1 receptor is also essential for inducing Ni allergy at both sensitization and elicitation steps, and (c) the 'sensitization to Ni' state may be a state where tissues are primed for augmented production of IL-1α and/or IL-1β in response to Ni. (within 300 words, now 300).

  25. Augmentation of Lipopolysaccharide-Induced Production of IL-1α and IL-1β in Mice Given Intravenous Zoledronate (a Nitrogen-Containing Bisphosphonate) and Its Prevention by Clodronate (a Non-nitrogen-containing Bisphosphonate). Peer-reviewed

    Suzuki H, Bando K, Tada H, Kiyama T, Oizumi T, Funayama H, Sugawara S, Takahashi T, Endo Y

    Biol Pharm Bull.　42　(2)　164-172　2019

    DOI： 10.1248/bpb.b18-00408 　

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    Bisphosphonates (BPs) bind strongly to bone and exhibit long-acting anti-bone-resorptive effects. Among BPs, nitrogen-containing BPs (N-BPs) have far stronger anti-bone-resorptive effects than non-N-BPs. However, N-BPs induce acute inflammatory reactions (fever, arthralgia and myalgia, etc.) after their first injection. The mechanisms underlying these side effects remain unclear. Zoledronate (one of the most potent N-BPs) is given intravenously to patients, and the side-effect incidence is reportedly the highest among N-BPs. Our murine experiments have clarified that (a) intraperitoneally injected N-BPs induce various inflammatory reactions, including a production of interleukin-1 (IL-1) (a typical inflammatory cytokine), and these inflammatory reactions are weak in IL-1-deficient mice, (b) subcutaneously injected N-BPs induce inflammation/necrosis at the injection site, (c) lipopolysaccharide (LPS; a cell-wall component of Gram-negative bacteria) and N-BPs mutually augment their inflammatory/necrotic effects, (d) the non-N-BP clodronate can reduce N-BPs' inflammatory/necrotic effects. However, there are few animal studies on the side effects of intravenously injected N-BPs. Here, we found in mice that (i) intravenous zoledronate exhibited weaker inflammatory effects than intraperitoneal zoledronate, (ii) in mice given intravenous zoledronate, LPS-induced production of IL-1α and IL-1β was augmented in various tissues, including bone, resulting in them increasing in serum, and (iii) clodronate (given together with zoledronate) prevented such augmentation and enhanced, slightly but significantly, zoledronate's anti-bone-resorptive effect. These results suggest that infection may be a factor promoting the acute inflammatory side effects of N-BPs via augmented production of IL-1 in various tissues (including bone), and that clodronate may be useful to reduce or prevent such side effects.

  26. Periodontal Regeneration by Allogeneic Transplantation of Adipose Tissue Derived Multi-Lineage Progenitor Stem Cells in vivo. International-journal Peer-reviewed

    Venkataiah VS, Handa K, Njuguna MM, Hasegawa T, Maruyama K, Nemoto E, Yamada S, Sugawara S, Lu L, Takedachi M, Murakami S, Okura H, Matsuyama A, Saito M

    Scientific reports　9　(1)　921-921　2019/01

    DOI： 10.1038/s41598-018-37528-0 　

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    The ultimate goal of periodontal disease treatment is the reorganization of functional tissue that can regenerate lost periodontal tissue. Regeneration of periodontal tissues is clinically possible by using autogenic transplantation of MSCs. However, autologous MSC transplantation is limited depending on age, systemic disease and tissue quality, thus precluding their clinical application. Therefore, we evaluated the efficacy of allogeneic transplantation of adipose-derived multi-lineage progenitor cells (ADMPC) in a micro-mini pig periodontal defect model. ADMPC were isolated from the greater omentum of micro-mini pigs, and flow cytometry analysis confirmed that the ADMPC expressed MSC markers, including CD44 and CD73. ADMPC exhibited osteogenic, adipogenic and periodontal ligament differentiation capacities in differentiation medium. ADMPC showed high expression of the immune suppressive factors GBP4 and IL1-RA upon treatment with a cytokine cocktail containing interferon-γ, tumor necrosis factor-α and interleukin-6. Allogeneic transplantation of ADMPC in a micro-mini pig periodontal defect model showed significant bone regeneration ability based on bone-morphometric analysis. Moreover, the regeneration ability of ADMPC by allogeneic transplantation was comparable to those of autologous transplantation by histological analysis. These results indicate that ADMPC have immune-modulation capability that can induce periodontal tissue regeneration by allogeneic transplantation.

  27. P.gingivalis感染によりマスト細胞から産生されたIL-31はclaudin-1発現抑制を介して歯肉上皮バリア破綻を誘導する

    多田 浩之, 沼崎 研人, 西岡 貴志, 松下 健二, 菅原 俊二

    Journal of Oral Biosciences Supplement　2018　202-202　2018/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  28. Roles of IL-1 alpha/beta in regeneration of cardiotoxin-injured muscle and satellite cell function Peer-reviewed

    Chaweewannakorn, Chayanit, Tsuchiya, Masahiro, Koide, Masashi, Hatakeyama, Hiroyasu, Tanaka, Yukinori, Yoshida, Shinichirou, Sugawara, Shunji, Hagiwara, Yoshihiro, Sasaki, Keiichi, Kanzaki, Makoto

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY　315　(1)　R90-R103　2018/07

    DOI： 10.1152/ajpregu.00310.2017 　

    ISSN： 0363-6119

    eISSN： 1522-1490

  29. Neutrophils Provide a Favorable IL-1-Mediated Immunometabolic Niche that Primes GLUT4 Translocation and Performance in Skeletal Muscles. International-journal Peer-reviewed

    Masahiro Tsuchiya, Shigenori Sekiai, Hiroyasu Hatakeyama, Masashi Koide, Chayanit Chaweewannakorn, Fukie Yaoita, Koichi Tan-No, Keiichi Sasaki, Makoto Watanabe, Shunji Sugawara, Yasuo Endo, Eiji Itoi, Yoshihiro Hagiwara, Makoto Kanzaki

    Cell reports　23　(8)　2354-2364　2018/05/22

    DOI： 10.1016/j.celrep.2018.04.067 　

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    Metabolic immunomodulation involving IL-1 has been investigated for unfavorable metabolic effects, including obesity, but a potentially favorable role for IL-1 remains unclear. Here, we find mechanistic interactions between working skeletal muscles and locally recruited neutrophils expressing IL-1β, which supports muscle performance through priming exercise-dependent GLUT4 translocation. Thus, during exercise, both IL-1α/β-deficient and neutrophil-depleted mice similarly exhibit increased fatigability associated with impaired muscle glucose homeostasis due to GLUT4 dysregulation. Deficiency of IL-1-producing neutrophils results in intrinsic abnormalities represented by aberrant Rac1 signaling and irregular GLUT4-storage vesicles, suggesting that these properties are maintained by local IL-1 produced by recruited neutrophils upon exercise, possibly on a daily basis. We propose that neutrophils are highly engaged in skeletal muscle performance via IL-1 regulation, which coordinates favorable inflammatory microenvironments supporting muscle glucose metabolism.

  30. CXCL4 is a novel nickel-binding protein and augments nickel allergy Peer-reviewed

    T. Kuroishi, K. Bando, Y. Tanaka, K. Shishido, M. Kinbara, T. Ogawa, K. Muramoto, Y. Endo, S. Sugawara

    CLINICAL AND EXPERIMENTAL ALLERGY　47　(8)　1069-1078　2017/08

    DOI： 10.1111/cea.12926 　

    ISSN： 0954-7894

    eISSN： 1365-2222

  31. Underlying Mechanisms and Therapeutic Strategies for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) Peer-reviewed

    Yasuo Endo, Hiroyuki Kumamoto, Masanori Nakamura, Shunji Sugawara, Teruko Takano-Yamamoto, Keiichi Sasaki, Tetsu Takahashi

    BIOLOGICAL & PHARMACEUTICAL BULLETIN　40　(6)　739-750　2017/06

    DOI： 10.1248/bpb.b16-01020 　

    ISSN： 0918-6158

  32. Mouse Model of Hydroquinone Hypersensitivity via Innate and Acquired Immunity and its Promotion by Combined Reagents Peer-reviewed

    Kanan Bando, Yukinori Tanaka, Toshinobu Kuroishi, Keiichi Sasaki, Teruko Takano-Yamamoto, Shunji Sugawara, Yasuo Endo

    JOURNAL OF INVESTIGATIVE DERMATOLOGY　137　(5)　1082-1093　2017/05

    DOI： 10.1016/j.jid.2016.12.018 　

    ISSN： 0022-202X

    eISSN： 1523-1747

  33. CD103(+)CD11b(-) salivary gland dendritic cells have antigen cross-presenting capacity Peer-reviewed

    Lu Lu, Yukinori Tanaka, Naoto Ishii, Takashi Sasano, Shunji Sugawara

    EUROPEAN JOURNAL OF IMMUNOLOGY　47　(2)　305-313　2017/02

    DOI： 10.1002/eji.201646631 　

    ISSN： 0014-2980

    eISSN： 1521-4141

  34. Pulmonary platelet accumulation induced by catecholamines: Its involvement in lipopolysaccharide-induced anaphylaxis-like shock Peer-reviewed

    Zhiqian Yu, Hiroko Saito, Hirotada Otsuka, Yosuke Shikama, Hiromi Funayama, Mai Sakai, Shigeo Murai, Masanori Nakamura, Takashi Yokochi, Haruhiko Takada, Shunji Sugawara, Yasuo Endo

    International Immunopharmacology　43　40-52　2017/02/01

    DOI： 10.1016/j.intimp.2016.11.034 　

    ISSN： 1567-5769

    eISSN： 1878-1705

  35. Oral CD103 - CD11b + classical dendritic cells present sublingual antigen and induce Foxp3 + regulatory T cells in draining lymph nodes Peer-reviewed

    Y. Tanaka, H. Nagashima, K. Bando, L. Lu, A. Ozaki, Y. Morita, S. Fukumoto, N. Ishii, S. Sugawara

    Mucosal Immunology　10　(1)　79-90　2017/01/01

    DOI： 10.1038/mi.2016.46 　

    ISSN： 1933-0219

    eISSN： 1935-3456

  36. Inflammatory Effects of Nitrogen-Containing Bisphosphonates (N-BPs): Modulation by Non-N-BPs Peer-reviewed

    Kazuhiro Shima, Masahiro Tsuchiya, Takefumi Oizumi, Teruko Takano-Yamamoto, Shunji Sugawara, Yasuo Endo

    BIOLOGICAL & PHARMACEUTICAL BULLETIN　40　(1)　25-33　2017/01

    DOI： 10.1248/bpb.b16-00521 　

    ISSN： 0918-6158

  37. 【アレルギー性疾患における免疫細胞の新たな役割とその制御機構】口腔CD103-CD11b+古典的樹状細胞は所属リンパ節で舌下投与された抗原を提示し、Foxp3+制御性T細胞を誘導する

    田中 志典, 福本 敏, 菅原 俊二

    臨床免疫・アレルギー科　66　(4)　364-370　2016/10

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  38. Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice Peer-reviewed

    Masayuki Kinbara, Kanan Bando, Daisuke Shiraishi, Toshinobu Kuroishi, Yasuhiro Nagai, Hiroshi Ohtsu, Teruko Takano-Yamamoto, Shunji Sugawara, Yasuo Endo

    EXPERIMENTAL DERMATOLOGY　25　(6)　466-471　2016/06

    DOI： 10.1111/exd.12985 　

    ISSN： 0906-6705

    eISSN： 1600-0625

  39. Phosphonocarboxylates Can Protect Mice against the Inflammatory and Necrotic Side Effects of Nitrogen-Containing Bisphosphonates by Inhibiting Their Entry into Cells via Phosphate Transporters Peer-reviewed

    Tomomi Kiyama, Masahiro Tsuchiya, Satoru Okada, Takefumi Oizumi, Kouji Yamaguchi, Keiichi Sasaki, Shunji Sugawara, Yasuo Endo

    BIOLOGICAL & PHARMACEUTICAL BULLETIN　39　(5)　712-720　2016/05

    DOI： 10.1248/bpb.b15-00770 　

    ISSN： 0918-6158

  40. Analgesic Effects of 1st Generation Anti-histamines in Mice. Peer-reviewed

    Takahashi M, Shima K, Tsuchiya M, Hagiwara Y, Mizoguchi H, Sakurada S, Sugawara S, Fujita T, Tadano T, Watanabe M, Fukumoto S, Endo Y

    Biological & pharmaceutical bulletin　39　(4)　620-624　2016

    DOI： 10.1248/bpb.b15-00755 　

    ISSN： 0918-6158

    eISSN： 1347-5215

  41. The Bisphosphonates Clodronate and Etidronate Exert Analgesic Effects by Acting on Glutamate- and/or ATP-Related Pain Transmission Pathways. Peer-reviewed

    Kazuhiro Shima, Wataru Nemoto, Masahiro Tsuchiya, Koichi Tan-No, Teruko Takano-Yamamoto, Shunji Sugawara, Yasuo Endo

    Biological & pharmaceutical bulletin　39　(5)　770-7　2016

    DOI： 10.1248/bpb.b15-00882 　

    ISSN： 0918-6158

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    Bisphosphonates (BPs) are typical anti-bone-resorptive drugs, with nitrogen-containing BPs (N-BPs) being stronger than non-nitrogen-containing BPs (non-N-BPs). However, N-BPs have inflammatory/necrotic effects, while the non-N-BPs clodronate and etidronate lack such side effects. Pharmacological studies have suggested that clodronate and etidronate can (i) prevent the side effects of N-BPs in mice via inhibition of the phosphate transporter families SLC20 and/or SLC34, through which N-BPs enter soft-tissue cells, and (ii) also inhibit the phosphate transporter family SLC17. Vesicular transporters for the pain transmitters glutamate and ATP belong to the SLC17 family. Here, we examined the hypothesis that clodronate and etidronate may enter neurons through SLC20/34, then inhibit SLC17-mediated transport of glutamate and/or ATP, resulting in their decrease, and thereby produce analgesic effects. We analyzed in mice the effects of various agents [namely, intrathecally injected clodronate, etidronate, phosphonoformic acid (PFA; an inhibitor of SLC20/34), and agonists of glutamate and ATP receptors] on the nociceptive responses to intraplantar injection of capsaicin. Clodronate and etidronate produced analgesic effects, and these effects were abolished by PFA. The analgesic effects were reduced by N-methyl-D-aspartate (agonist of the NMDA receptor, a glutamate receptor) and α,β-methylene ATP (agonist of the P2X-receptor, an ATP receptor). SLC20A1, SLC20A2, and SLC34A1 were detected within the mouse lumbar spinal cord. Although we need direct evidence, these results support the above hypothesis. Clodronate and etidronate may be representatives of a new type of analgesic drug. Such drugs, with both anti-bone-resorptive and unique analgesic effects without the adverse effects associated with N-BPs, might be useful for osteoporosis.

  42. A strategy against the osteonecrosis of the jaw associated with Nitrogen-Containing Bisphosphonates (N-BPs): Attempts to replace N-BPs with the non-N-BP etidronate Peer-reviewed

    Takefumi Oizumi, Kouji Yamaguchi, Koichiro Sato, Masato Takahashi, Gen Yoshimura, Hiroshi Otsuru, Masahiro Tsuchiya, Yoshihiro Hagiwara, Eiji Itoi, Shunji Sugawara, Tetsu Takahashi, Yasuo Endo

    Biological and Pharmaceutical Bulletin　39　(9)　1549-1554　2016

    DOI： 10.1248/bpb.b16-00041 　

    ISSN： 0918-6158

    eISSN： 1347-5215

  43. Transportation of sublingual antigens across sublingual ductal epithelial cells to the ductal antigen-presenting cells in mice. Peer-reviewed

    Nagai, Yasuhiro, Shiraishi, Daisuke, Tanaka, Yukinori, Nagasawa, Yuya, Ohwada, Shyuichi, Shimauchi, Hidetoshi, Aso, Hisashi, Endo, Yasuo, Sugawara, Shunji

    Clinical & Experimental Allergy　45(3) : 677-86　(3)　677-686　2015/02/07

    DOI： 10.1111/cea.12329 　

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    4. Nagai, Yasuhiro; Shiraishi, Daisuke; Tanaka, Yukinori; Nagasawa, Yuya; Ohwada, Shyuichi; Shimauchi, Hidetoshi; Aso, Hisashi; Endo, Yasuo; Sugawara, Shunji: Transportation of sublingual antigens across sublingual ductal epithelial cells to the ductal antigen-presenting cells in mice. Clinical &amp; Experimental Allergy, 45(3) : 677-86, 2014. (DOI: 10.1111/cea.12329) (IF = 4.789)

  44. Involvement of IL-1 in the Maintenance of Masseter Muscle Activity and Glucose Homeostasis. International-journal Peer-reviewed

    Chiba K, Tsuchiya M, Koide M, Hagiwara Y, Sasaki K, Hattori Y, Watanabe M, Sugawara S, Kanzaki M, Endo Y

    PloS one　10　(11)　e0143635　2015

    DOI： 10.1371/journal.pone.0143635 　

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    Physical exercise reportedly stimulates IL-1 production within working skeletal muscles, but its physiological significance remains unknown due to the existence of two distinct IL-1 isoforms, IL-1α and IL-1β. The regulatory complexities of these two isoforms, in terms of which cells in muscles produce them and their distinct/redundant biological actions, have yet to be elucidated. Taking advantage of our masticatory behavior (Restrained/Gnawing) model, we herein show that IL-1α/1β-double-knockout (IL-1-KO) mice exhibit compromised masseter muscle (MM) activity which is at least partially attributable to abnormalities of glucose handling (rapid glycogen depletion along with impaired glucose uptake) and dysfunction of IL-6 upregulation in working MMs. In wild-type mice, masticatory behavior clearly increased IL-1β mRNA expression but no incremental protein abundance was detectable in whole MM homogenates, whereas immunohistochemical staining analysis revealed that both IL-1α- and IL-1β-immunopositive cells were recruited around blood vessels in the perimysium of MMs after masticatory behavior. In addition to the aforementioned phenotype of IL-1-KO mice, we found the IL-6 mRNA and protein levels in MMs after masticatory behavior to be significantly lower in IL-1-KO than in WT. Thus, our findings confirm that the locally-increased IL-1 elicited by masticatory behavior, although present small in amounts, contributes to supporting MM activity by maintaining normal glucose homeostasis in these muscles. Our data also underscore the importance of IL-1-mediated local interplay between autocrine myokines including IL-6 and paracrine cytokines in active skeletal muscles. This interplay is directly involved in MM performance and fatigability, perhaps mediated through maintaining muscular glucose homeostasis.

  45. Resin Monomers Act as Adjuvants in Ni-induced Allergic Dermatitis in vivo Peer-reviewed

    K. Bando, H. Takahashi, M. Kinbara, Y. Tanaka, T. Kuroishi, K. Sasaki, T. Takano-Yamamoto, S. Sugawara, Y. Endo

    JOURNAL OF DENTAL RESEARCH　93　(11)　1101-1107　2014/11

    DOI： 10.1177/0022034514552674 　

    ISSN： 0022-0345

    eISSN： 1544-0591

  46. レジンモノマーはアジュバントとして歯科材料アレルゲンによるマウスでのアレルギーを促進する

    坂東 加南, 山本 照子, 菅原 俊二, 遠藤 康男

    日本矯正歯科学会大会プログラム・抄録集　73回　185-185　2014/10

    Publisher: (公社)日本矯正歯科学会

  47. Long-term feeding on powdered food causes hyperglycemia and signs of systemic illness in mice. International-journal Peer-reviewed

    Tsuchiya M, Niijima-Yaoita F, Yoneda H, Chiba K, Tsuchiya S, Hagiwara Y, Sasaki K, Sugawara S, Endo Y, Tan-No K, Watanabe M

    Life sciences　103　(1)　8-14　2014/05

    DOI： 10.1016/j.lfs.2014.03.022 　

    ISSN： 0024-3205

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    AIMS: Dietary habits are crucial factors affecting metabolic homeostasis. However, few animal experiments have addressed the effects of long-term feeding with soft food on parameters reflecting systemic health. MAIN METHODS: Using mice, we compared the effects of short (3 days) and long (17 weeks from weaning) feeding periods between powdered food and normal pellet food on the levels of blood glucose, serum levels of insulin, catecholamines, and corticosterone, blood pressure, and/or social interaction behaviors. In addition, the effects of a human glucagon-like peptide-1 analog, liraglutide (a new drug with protective effects against neuronal and cardiovascular diseases), were compared between the powder and pellet groups. KEY FINDING: (i) Powdered food, even for such a short period, resulted in a greater glycemic response than pellet food, consistent with powdered food being more easily digested and absorbed. (ii) Long-term feeding on powdered food induced hyperglycemia and related systemic signs of illness, including increases in serum adrenaline, noradrenaline, and corticosterone, higher blood pressures (especially diastolic), and increased social interaction behaviors. (iii) Liraglutide, when administered subcutaneously for the last 2 weeks of the 17-week period of feeding, improved these changes (including those in social interaction behaviors). SIGNIFICANCE: The hyperglycemia associated with long-term powdered-food feeding may lead to certain systemic illness signs, such as elevations of blood glucose, hypertension, and abnormal behaviors in mice. Mastication of food of adequate hardness may be very important for the maintenance of systemic (physical and mental) health, possibly via reduction in the levels of blood glucose and/or adrenal stress hormones (catecholamines and glucocorticoids).

  48. Increased Interleukin-18 in the Gingival Tissues Evokes Chronic Periodontitis after Bacterial Infection Peer-reviewed

    Kotaro Yoshinaka, Noriaki Shoji, Takashi Nishioka, Yumiko Sugawara, Tomoaki Hoshino, Shunji Sugawara, Takashi Sasano

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　232　(3)　215-222　2014/03

    DOI： 10.1620/tjem.232.215 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  49. Inhibition of phosphate transporters ameliorates the inflammatory and necrotic side effects of the nitrogen-containing bisphosphonate zoledronate in mice. Peer-reviewed

    Okada S, Kiyama T, Sato E, Tanaka Y, Oizumi T, Kuroishi T, Takahashi T, Sasaki K, Sugawara S, Endo Y

    The Tohoku journal of experimental medicine　231　(2)　145-158　2013/10

    DOI： 10.1620/tjem.231.145 　

    ISSN： 0040-8727

    eISSN： 1349-3329

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    Bisphosphonates (BPs) are pyrophosphate analogs. They are widely used against enhanced bone-resorption in various diseases. Nitrogen-containing BPs (N-BPs) exhibit strong anti-bone-resorptive effects but have inflammatory and necrotic side effects. The non-nitrogen-containing BPs (non-N-BPs) etidronate and clodronate lack such side effects, but their anti-bone-resorptive effects are weak. In mice, etidronate and clodronate reduce the inflammatory/necrotic effects of N-BPs, even those of zoledronate, the N-BP with the strongest anti-bone-resorptive effect yet reported and the highest risk of inflammation/necrosis. Here, to explore the mechanisms underlying this protection, we used a mouse model in which a single reagent or a mixture of two reagents was injected subcutaneously into ear-pinnas. These reagents included zoledronate, four non-N-BPs, pyrophosphate, and inhibitors of various organic-anion-transporters. Pyrophosphate and two of the four non-N-BPs (not etidronate or clodronate) had inflammatory/necrotic effects. These effects were reduced by etidronate and clodronate, but not by phosphonoformate, an inhibitor of two of the three known phosphate-transporter families. Phosphonoformate reduced the inflammatory/necrotic effects of zoledronate, but not those of pyrophosphate or of non-N-BPs. Conversely, pyrophosphate, at non-inflammatory/necrotic concentrations, reduced the inflammatory/necrotic effects of non-N-BPs, but not those of zoledronate. The efficacies of the protective effects against the inflammatory/necrotic effects of zoledronate were clodronate > etidronate > phosphonoformate. These findings suggest that (i) the N-BP zoledronate may enter soft-tissue cells via phosphonoformate-inhibitable phosphate-transporters, (ii) other phosphate-transporters may carry pyrophosphate and inflammatory/necrotic non-N-BPs into such cells, and (iii) etidronate and clodronate inhibit all these transporters, and they ameliorate the side effects of zoledronate by inhibiting phosphonoformate-inhibitable phosphate-transporters.

  50. Metal allergens induce nitric oxide production by mouse dermal fibroblasts via the hypoxia-inducible factor-2α-dependent pathway. International-journal Peer-reviewed

    Kuroishi T, Bando K, Endo Y, Sugawara S

    Toxicological sciences : an official journal of the Society of Toxicology　135　(1)　119-128　2013/09

    DOI： 10.1093/toxsci/kft142 　

    ISSN： 1096-6080

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    Nickel (Ni) has been shown to be one of the most frequent metal allergens. We have already reported a murine metal allergy model with pathogen-associated molecular patterns (PAMPs) as adjuvants. Interleukin (IL)-1β plays a critical role in our mouse model. Because nonimmune cells, including fibroblasts, play important roles in local allergic inflammation, we investigated whether Ni induces inflammatory responses in mouse dermal fibroblasts (MDF). We also analyzed the synergistic effects between Ni, PAMPs, and IL-1β. MDF stimulated with Ni produced a significantly higher amount of nitric oxide (NO) in a dose-dependent manner. NO production was augmented by costimulation with IL-1β but not with PAMPs. On the other hand, IL-1β or PAMPs induced a significantly higher amount of IL-6 production by MDF, but no augmentation was detected in the presence of Ni. A specific inhibitor for inducible nitric oxide synthase (iNOS) inhibited Ni-induced NO production. iNOS mRNA expression was significantly higher in MDF stimulated with Ni, IL-1β, or both. A specific inhibitor for hypoxia-inducible factor (HIF)-2α, but not HIF-1α, inhibited NO production. Another frequent metal allergen, cobalt, also induced iNOS expression and NO production by MDF via the HIF-2α-dependent pathway. The inhibitor for iNOS augmented ear swelling in Ni allergy mouse model. On the other hand, HIF-2α inhibitor attenuates allergic inflammation. These results indicate that metal allergens induce NO production in MDF via the HIF-2α-dependent pathway and IL-1β augments NO production, which suggests that the NO induced by metal allergens plays a pathological role in metal allergies.

  51. 【アナフィラキシス】アナフィラキシーにおける好塩基球および好中球の役割

    田中 志典, 遠藤 康男, 菅原 俊二

    アレルギー・免疫　20　(8)　1126-1136　2013/07

    Publisher: (株)医薬ジャーナル社

    ISSN： 1344-6932

  52. Inflammatory and Necrotic Effects of Minodronate, a Nitrogen-Containing Bisphosphonate, in Mice Peer-reviewed

    Tomomi Kiyama, Satoru Okada, Yukinori Tanaka, Siyoung Kim, Kanan Bando, Masakazu Hasegawa, Kouji Yamaguchi, Teruko Takano-Yamamoto, Keiichi Sasaki, Shunji Sugawara, Yasuo Endo

    TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　230　(3)　141-149　2013/07

    DOI： 10.1620/tjem.230.141 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  53. In vitro cytotoxicity of zoledronate (nitrogen-containing bisphosphonate: NBP) and/or etidronate (non-NBP) in tumour cells and periodontal cells. Peer-reviewed

    Tanaka Y, Nagai Y, Dohdoh M, Oizumi T, Ohki A, Kuroishi T, Sugawara S, Endo Y

    Archives of oral biology　58　(6)　628-637　2013/06

    DOI： 10.1016/j.archoralbio.2012.11.010 　

    ISSN： 0003-9969

  54. Prime role of bone IL-1 in mice may lie in emergency Ca(2+)-supply to soft tissues, not in bone-remodeling. International-journal Peer-reviewed

    Deng X, Oguri S, Funayama H, Ohtaki Y, Ohsako M, Yu Z, Sugawara S, Endo Y

    International immunopharmacology　14　(4)　658-664　2012/10

    Publisher: 4

    DOI： 10.1016/j.intimp.2012.10.001 　

    ISSN： 1567-5769

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    IL-1 and TNF-α are thought to be important bone-remodeling regulators. However, mice lacking either them or their receptors reportedly grow healthily. Here, we examined the roles of IL-1 and TNF-α in bone. Although a significant IL-1 level was detected in the tibia of non-stimulated wild-type (WT) mice, no significant physicochemical, morphological, or histological defects were detected in the tibias in mice lacking IL-1 (both α and β types) (IL-1KO) or lacking both IL-1 and TNF-α (IL-1/TNF-αKO). Injection of sub-lethal doses of lipopolysaccharide (LPS) into WT mice induced a transient hypocalcemia, increased IL-1 (in the plasma and markedly in the tibia), and increased TNF-α (markedly in the plasma, but only slightly in the tibia). LPS-induced hypocalcemia was modest in IL-1KO mice, and not detected in IL-1/TNFαKO mice. IL-1α (but not TNFα) induced hypocalcemia in both WT and IL-1KO mice. In both WT and IL-1KO mice treated with clodronate (osteoclast inhibitor), the LPS-induced hypocalcemia was markedly augmented. Nifedipine (inhibitor of both voltage-activated and capacitative Ca(2+)-entry) reduced the LPS-induced hypocalcemia. These results suggest that in mice: (i) IL-1 and TNF-α may contribute little to physiological bone-formation, and (ii) a time-lag between IL-1- and TNF-α-stimulated Ca(2+)-entry into cells throughout the body from the circulation and IL-1-stimulated Ca(2+)-release from the bone may cause the observed transient LPS-induced hypocalcemia. Thus, the prime role of bone IL-1 may reside in the supply of Ca(2+) from the bone to cells throughout the body when the need is urgent.

  55. レジンモノマー重合防止剤ハイドロキノンによるマウスでのアレルギー

    坂東 加南, 田中 志典, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2012　110-110　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  56. Interleukin-6 maintains glucose homeostasis to support strenuous masseter muscle activity in mice. Peer-reviewed

    Tsuchiya M, Kiyama T, Tsuchiya S, Takano H, Nemoto E, Sasaki K, Watanabe M, Sugawara S, Endo Y

    The Tohoku journal of experimental medicine　227　(2)　109-117　2012/06

    ISSN： 0040-8727

  57. Histamine reduces susceptibility to natural killer cells via down-regulation of NKG2D ligands on human monocytic leukaemia THP-1 cells. Peer-reviewed

    Nagai Yasuhiro, Tanaka Yukinori, Kuroishi Toshinobu, Sato Ryutaro, Endo Yasuo, Sugawara Shunji

    Immunology　136　(1)　103-114　2012/05

    DOI： 10.1111/j.1365-2567.2012.03565.x 　

    ISSN： 0019-2805

  58. Stimulation of Ly-6G on neutrophils in LPS-primed mice induces platelet-activating factor (PAF)-mediated anaphylaxis-like shock. Peer-reviewed

    Tanaka Yukinori, Nagai Yasuhiro, Kuroishi Toshinobu, Endo Yasuo, Sugawara Shunji

    J Leukoc Biol　91　(3)　485-494　2012/03

    DOI： 10.1189/jlb.1210697 　

    ISSN： 0741-5400

  59. Antagonism between bisphosphonates (BPs) and structurally related substances in the effects of BPs in mice Peer-reviewed

    Satoru Okada, Tomomi Kiyama, Takefumi Oizumi, Kouji Yamaguchi, Hiroshi Kawamura, Shunji Sugawara, Yasuo Endo

    Interface Oral Health Science 2011　235-236　2012/01/01

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-54070-0_66 　

  60. Metal-allergy cross-reactions in mice Peer-reviewed

    Masayuki Kinbara, Yasuhiro Nagai, Teruko Takano-Yamamoto, Shunji Sugawara, Yasuo Endo

    Interface Oral Health Science 2011　95-96　2012/01/01

    Publisher: Springer Japan

    DOI： 10.1007/978-4-431-54070-0_17 　

  61. Roles of histamine in exercise-induced fatigue: favouring endurance and protecting against exhaustion. Peer-reviewed

    Niijima-Yaoita F, Tsuchiya M, Ohtsu H, Yanai K, Sugawara S, Endo Y, Tadano T

    Biological & pharmaceutical bulletin　35　(1)　91-97　2012

    Publisher: 1

    DOI： 10.1248/bpb.35.91 　

    ISSN： 0918-6158 1347-5215

    eISSN： 1347-5215

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    Exercise necessitates a large supply of O(2) and nutrients and rapid removal of CO(2) and waste products. Histamine is a regulator of the microcirculation (which performs these exchanges), suggesting a possible involvement of histamine in exercise. Histamine is released from either mast cells or non-mast cells. In the latter, histamine is newly formed via the induction of histidine decarboxylase (HDC) in response to an appropriate stimulus, and it is released without being stored. Here, in mice, we examined the role of histamine or HDC induction in exercise. Prolonged walking (PW) (in a cylindrical cage turned electrically) increased HDC mRNA and HDC activity in quadriceps femoris muscles. Mice given a histamine H1-receptor antagonist [fexofenadine (peripherally acting) or pyrilamine (peripherally and centrally acting)] or an irreversible HDC inhibitor (α-fluoromethylhistidine) displayed less PW endurance than control mice. Ranitidine (H2-receptor antagonist) tended to reduce endurance. Other histamine-receptor (H3 and H4) antagonists had no significant effects on endurance. Mice deficient in HDC or histamine H1-receptors displayed markedly less endurance than control mice, and HDC activity in the quadriceps femoris of H1-deficient mice was rapidly elevated by PW. Fexofenadine significantly reduced the muscle levels of nitric oxide (NO) metabolites and glycogen after PW. The results support the ideas that (i) histamine is involved in protecting against exercise-induced fatigue or exhaustion, (ii) histamine exerts its protective effect via H1 receptors and the ensuing production of NO in skeletal muscle, and (iii) histamine is provided, at least in part, by HDC induction in skeletal muscles during prolonged exercise.

  62. Nickel allergy-promoting effects of microbial or inflammatory substances at the sensitization step in mice Peer-reviewed

    Harue Takahashi, Masayuki Kinbara, Naoki Sato, Keiichi Sasaki, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　11　(10)　1534-1540　2011/10

    DOI： 10.1016/j.intimp.2011.05.010 　

    ISSN： 1567-5769

    eISSN： 1878-1705

  63. Roles of platelets and macrophages in the protective effects of lipopolysaccharide against concanavalin A-induced murine hepatitis Peer-reviewed

    Zhiqian Yu, Hirotada Otsuka, Kouji Yamaguchi, Toshinobu Kuroishi, Takashi Sasano, Shunji Sugawara, Masanori Nakamura, Yasuo Endo

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE　1812　(9)　1069-1079　2011/09

    DOI： 10.1016/j.bbadis.2011.06.005 　

    ISSN： 0925-4439

  64. Roles of platelets and macrophages in the protective effects of lipopolysaccharide against concanavalin A-induced murine hepatitis. Peer-reviewed

    Yu Z, Otsuka H, Yamaguchi K, Kuroishi T, Sasano T, Sugawara S, Nakamura M, Endo Y

    Biochimica et biophysica acta　2011/06

    DOI： 10.1016/j.bbadis.2011.06.005 　

    ISSN： 0006-3002

  65. The elicitation step of nickel allergy is promoted in mice by microbe-related substances, including some from oral bacteria. Peer-reviewed

    Huang L, Kinbara M, Funayama H, Takada H, Sugawara S, Endo Y

    11　1916-1924　2011

    DOI： 10.1016/j.intimp.2011.07.025 　

  66. Pro-IL-1β accumulation in macrophages by alendronate and its prevention by clodronate. Peer-reviewed

    Shikama Y, Nagai Y, Okada S, Oizumi T, Shimauchi H, Sugawara S, Endo Y

    Toxicology letters　199　(2)　123-128　2010/11

    DOI： 10.1016/j.toxlet.2010.08.013 　

    ISSN： 0378-4274

  67. 細胞外ATPによる唾液腺導管上皮細胞表面へのMHC class II分子の表出誘導

    伊藤 あゆみ, 永井 康裕, 菅原 由美子, 菅原 俊二

    Journal of Oral Biosciences　52　(Suppl)　109-109　2010/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  68. Retraction: Proinflammatory cytokines induce proteinase 3 as membrane-bound and secretory forms in human oral epithelial cells and antibodies to proteinase 3 activate the cells through protease-activated receptor-2. Peer-reviewed

    Sugawara Yumiko, Sasano Takashi, Sugawara Shunji

    J Immunol　184　(7)　4044-4044　2010/04/01

    DOI： 10.4049/jimmunol.1090013 　

  69. Anaphylaxis-like shock induced by LPS plus antineutrophil monoclonal antibodies in mice Peer-reviewed

    Yukinori Tanaka, Yasuhiro Nagai, Toshinobu Kuroishi, Haruhiko Takada, Yasuo Endo, Shunji Sugawara

    INTERFACE ORAL HEALTH SCIENCE 2009　223-+　2010

    DOI： 10.1007/978-4-431-99644-6_55 　

  70. Analysis of antigen incorporating and processing cells in sublingal immunotherapy Peer-reviewed

    Daisuke Shiraishi, Yasuhiro Nagai, Yasuo Endo, Hidetoshi Shimauchi, Shunji Sugawara

    INTERFACE ORAL HEALTH SCIENCE 2009　277-+　2010

    DOI： 10.1007/978-4-431-99644-6_78 　

  71. Induction of Tregs from PBMC by interacting with immunosuppressive molecule B7-H3 on oral mesenchymal stem cells Peer-reviewed

    Yasuhiro Nagai, Toshinobu Kuroishi, Daisuke Shiraishi, Akiko Ohki, Shunji Sugawara

    INTERFACE ORAL HEALTH SCIENCE 2009　234-236　2010

    DOI： 10.1007/978-4-431-99644-6_60 　

  72. Muramyldipeptide augments the actions of LPS via multiple fashions in mice Peer-reviewed

    Yosuke Shikama, Toshinobu Kuroishi, Yasuhiro Nagai, Hidetoshi Shimauchi, Haruhiko Takada, Shunji Sugawara, Yasuo Endo

    INTERFACE ORAL HEALTH SCIENCE 2009　227-+　2010

    DOI： 10.1007/978-4-431-99644-6_57 　

  73. Prevention of necrotic actions of nitrogen-containing bisphosphonates (NBPs) in mice by non-NBPs (clodronate and etidronate) Peer-reviewed

    Takefumi Oizumi, Kouji Yamaguchi, Hiromi Funayama, Hiroshi Kawamura, Shunji Sugawara, Yasuo Endo

    INTERFACE ORAL HEALTH SCIENCE 2009　116-118　2010

    DOI： 10.1007/978-4-431-99644-6_17 　

  74. Concentrations of metal ions in murine nickel allergy and its cross-reactions: effects of lipopolysaccharide Peer-reviewed

    Masayuki Kinbara, Toshinobu Kuroishi, Teruko Takano-Yamamoto, Shunji Sugawara, Yasuo Endo

    INTERFACE ORAL HEALTH SCIENCE 2009　225-+　2010

    DOI： 10.1007/978-4-431-99644-6_56 　

  75. Promotion of arthritis and allergy in mice by aminoglycoglycerophospholipid, a membrane antigen specific to Mycoplasma fermentans. Peer-reviewed

    Sato N, Oizumi T, Kinbara M, Sato T, Funayama H, Sato S, Matsuda K, Takada H, Sugawara S, Endo Y

    59　(1)　33-41　2010

    DOI： 10.1111/j.1574-695X.2010.00657.x 　

  76. Inhibition of necrotic actions of nitrogen-containing bisphosphonates (NBPs) and their elimination from bone by etidronate (a non-NBP): a proposal for possible utilization of etidronate as a substitution drug for NBPs. International-journal Peer-reviewed

    Takefumi Oizumi, Hiromi Funayama, Kouji Yamaguchi, Masayoshi Yokoyama, Harue Takahashi, Miou Yamamoto, Toshinobu Kuroishi, Hiroyuki Kumamoto, Keiichi Sasaki, Hiroshi Kawamura, Shunji Sugawara, Yasuo Endo

    Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons　68　(5)　1043-1054　2010

    DOI： 10.1016/j.joms.2009.08.027 　

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    PURPOSE: Nitrogen-containing bisphosphonates (NBPs) have powerful anti-bone-resorptive effects (ABREs). However, recent clinical applications have disclosed an unexpected side effect, osteonecrosis of the jaw. We previously found in mice that etidronate (a non-NBP), when coadministered with alendronate (an NBP), inhibited the latter's inflammatory effects. However, etidronate also reduced the ABRE of alendronate. The present study examined in mice the modulating effects of etidronate on the inflammatory and necrotic actions of zoledronate (the NBP with the strongest anti-bone-resorptive activity and the highest incidence of osteonecrosis of the jaw) and on ABREs of various NBPs including zoledronate. MATERIALS AND METHODS: NBPs were subcutaneously injected into ear pinnas of mice and ensuing inflammation and necrosis at the site of the injection were evaluated. ABREs of NBPs were evaluated by analyzing sclerotic bands induced in mouse tibias. RESULTS: Coinjection of etidronate reduced inflammatory and necrotic reactions induced by zoledronate, and also reduced the amount of zoledronate retained within the ear tissue. When both agents were intraperitoneally injected, etidronate reduced the ABRE of zoledronate and those of other NBPs. Notably, etidronate reduced the ABRE of zoledronate even when this non-NBP was injected 16 hours after the injection of zoledronate. Bone scintigram indicated that etidronate reduced the amount of zoledronate that had already bound to bone. CONCLUSIONS: These results suggest that etidronate may 1) inhibit the entry of NBPs into cells related to inflammation and/or necrosis, 2) inhibit the binding of NBPs to bone hydroxyapatite, 3) at least partly eliminate (or substitute for) NBPs that have already accumulated within bones, and thus 4) if used as a substitution drug for NBPs, be effective at treating or preventing NBP-associated osteonecrosis of the jaw.

  77. Osteonecrosis of the jawbones in 2 osteoporosis patients treated with nitrogen-containing bisphosphonates: osteonecrosis reduction replacing NBP with non-NBP (etidronate) and rationale. Peer-reviewed

    Yamaguchi K, Oizumi T, Funayama H, Kawamura H, Sugawara S, Endo Y

    J. Oral Maxillofac. Surg.　68　889-897　2010

    DOI： 10.1016/j.joms.2009.04.048 　

  78. Pharmacological characterization of anaphylaxis-like shock responses induced in mice by mannan and lipopolysaccharide. Peer-reviewed

    Funayama H, Huang L, Sato T, Ohtaki Y, Asada Y, Yokochi T, Takada H, Sugawara S, Endo Y

    9　1518-1524　2010

    DOI： 10.1016/j.intimp.2009.09.006 　

  79. Dynamics of platelet mobilisation into lungs in response to 5-hydroxytryptamine (serotonin) in mice. Peer-reviewed

    Yu Z, Ohba M, Nakamura M, Sasano T, Ono M, Sugawara S, Endo Y

    Thrombosis and haemostasis　102　1251-1258　2009/12

    Publisher: 6

    DOI： 10.1160/TH08-06-0406 　

    ISSN： 0340-6245

  80. マウスでのニッケルアレルギー 片耳感作が両耳におよぼす効果

    坂東 加南, 金原 正敬, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　51　(Suppl.)　72-72　2009/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  81. Retraction: Endogenous IL-15 sustains recruitment of IL-2Rbeta and common gamma and IL-2-mediated chemokine production in normal and inflamed human gingival fibroblasts. Peer-reviewed

    Ozawa Akiko, Tada Hiroyuki, Sugawara Yumiko, Uehara Akiko, Sasano Takashi, Shimauchi Hidetoshi, Takada Haruhiko, Sugawara Shunji

    J Immunol　183　(3)　2193-2193　2009/08/01

    DOI： 10.4049/jimmunol.0990052 　

  82. Hepatic platelet accumulation in Fas-mediated hepatitis in mice International-journal Peer-reviewed

    Ohtaki Y, Yamaguchi K, Yu Z, Kumamoto H, Shimauchi H, Iwakura Y, Sugawara S, Endo Y

    International Immunopharmacology　9　(9)　1071-1078　2009/08

    DOI： 10.1016/j.intimp.2009.04.016 　

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    Platelets are reported to be causally involved in experimental hepatitis. Jo2, an agonistic anti-Fas antibody, induces hepatitis in mice. We examined the in vivo behaviors of platelets in mice injected with this antibody (analyzed by measuring 5-hydroxytryptamine, a constituent of platelets). We found that Jo2 induces platelet accumulation predominantly in the liver, and that this hepatic platelet accumulation (HPA) precedes the increases in hepatitis markers (alanine- and asparagine-aminotransferases [ALT and AST]). By electron microscopy, we detected entry of platelets into hepatocytes, and also evidence of apoptosis among hepatocytes. A caspases-3/6/7/8/10 inhibitor prevented the Jo2-induced HPA and hepatitis. In platelet-depleted mice, contrary to our expectations, the Jo2-induced hepatitis was not reduced, and actually the increase in AST was significantly augmented, although the survival time of mice given a lethal dose of Jo2 was significantly increased (nearly doubled). Interestingly, prior induction of HPA by a low dose of lipopolysaccharide markedly reduced Jo2-induced hepatitis. Jo2 also induced HPA and hepatitis in mice deficient in both IL-1 and TNFalpha, although Jo2 increased the blood level of TNFalpha in wild-type mice. These results suggest that in Jo2-induced hepatitis: (i) platelets accumulate predominantly in the liver as a result of hepatic lesions, and that this precedes the release of transaminases from hepatocytes, and (ii) IL-1 and TNFalpha are not essential for Jo2-hepatitis. We hypothesize that platelet accumulation in the liver may, contrary to our expectations, be protective when the hepatitis is local or not severe, but harmful when hepatitis is severe.

  83. Necrotic actions of nitrogen-containing bisphosphonates (NBPs) and their inhibition by clodronate (a non-NBP) in mice: potential for utilization of clodronate as a combination drug with an NBP. Peer-reviewed

    Oizumi T, Yamaguchi K, Funayama H, Kuroishi T, Kawamura H, Sugawara S, Endo Y

    Basic Clin Pharmacol Toxicol　104　(5)　384-392　2009

    DOI： 10.1111/j.1742-7843.2008.00374.x 　

  84. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjogren's syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. Peer-reviewed

    Sakai Azusa, Sugawara Yumiko, Kuroishi Toshinobu, Sasano Takashi, Sugawara Shunji

    J Immunol　181　(4)　2898-2906　2008/08/15

  85. Biotin deficiency up-regulates TNF-alpha production in murine macrophages Peer-reviewed

    Toshinobu Kuroishi, Yasuo Endo, Koji Muramoto, Shunji Sugawara

    JOURNAL OF LEUKOCYTE BIOLOGY　83　(4)　912-920　2008/04

    DOI： 10.1189/jlb.0607428 　

    ISSN： 0741-5400

  86. IL-18 expressed in salivary gland cells induces IL-6 and IL-8 in the cells in synergy with IL-17 Peer-reviewed

    Azusa Sakai Toshinobu, Kuroishi Yumiko Sugawara, Takashi Sasano, Shunji Sugawara

    Interface Oral Health Science　287-288　2008/02/01

  87. Histamine amplifies immune response of gingival fibroblasts Peer-reviewed

    T. Minami, T. Kuroishi, A. Ozawa, H. Shimauchi, Y. Endo, S. Sugawara

    JOURNAL OF DENTAL RESEARCH　86　(11)　1083-1088　2007/11

    DOI： 10.1177/154405910708601112 　

    ISSN： 0022-0345

  88. Oral bacterial lipopolysaccharide acts in mice to promote sensitisation to ovalbumin and to augment anaphylaxis via platelets Peer-reviewed

    Atsushi Yoshida, Xue Deng, Takashi Sasano, Haruhiko Takada, Shunji Sugawara, Yasuo Endo

    ARCHIVES OF ORAL BIOLOGY　52　(10)　990-994　2007/10

    DOI： 10.1016/j.archoralbio.2007.04.001 　

    ISSN： 0003-9969

  89. Induction of serum IL-18 with Propionibacterium acnes and lipopolysaccharide in phagocytic macrophage-inactivated mice Peer-reviewed

    Takashi Nishioka, Toshinobu Kuroishi, Yumiko Sugawara, Zhiqian Yu, Takashi Sasano, Yasuo Endo, Shunji Sugawara

    JOURNAL OF LEUKOCYTE BIOLOGY　82　(2)　327-334　2007/08

    DOI： 10.1189/jlb.1006598 　

    ISSN： 0741-5400

    eISSN： 1938-3673

  90. Lipopolysaccharide promotes and augments metal allergies in mice, dependent on innate immunity and histidine decarboxylase Peer-reviewed

    N. Sato, M. Kinbara, T. Kuroishi, K. Kimura, Y. Iwakura, H. Ohtsu, S. Sugawara, Y. Endo

    CLINICAL AND EXPERIMENTAL ALLERGY　37　(5)　743-751　2007/05

    DOI： 10.1111/j.1365-2222.2007.02705.x 　

    ISSN： 0954-7894

    eISSN： 1365-2222

  91. Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis patients Peer-reviewed

    Ken-ichi Komine, Toshinobu Kuroishi, Akiko Ozawa, Yumiko Komine, Takumi Minami, Hidetoshi Shimauchi, Shunji Sugawara

    MOLECULAR IMMUNOLOGY　44　(7)　1498-1508　2007/03

    DOI： 10.1016/j.molimm.2006.09.003 　

    ISSN： 0161-5890

  92. Human parotid saliva contains soluble toll-like receptor (TLR) 2 and modulates TLR2-mediated interleukin-8 production by monocytic cells Peer-reviewed

    Toshinobu Kuroishi, Yukinori Tanaka, Azusa Sakai, Yumiko Sugawara, Ken-Ichi Komine, Shunji Sugawara

    MOLECULAR IMMUNOLOGY　44　(8)　1969-1976　2007/03

    DOI： 10.1016/j.molimm.2006.09.028 　

    ISSN： 0161-5890

  93. Histidine decarboxylase-stimulating and inflammatory effects of alendronate in mice: Involvement of mevalonate pathway, TNF alpha, macrophages, and T-cells Peer-reviewed

    Xue Deng, Zhiqian Yu, Hiromi Funayama, Kouji Yamaguchi, Takashi Sasano, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　7　(2)　152-161　2007/02

    DOI： 10.1016/j.intimp.2006.09.009 　

    ISSN： 1567-5769

  94. Inductions of histidine decarboxylase in mouse tissues following systemic antigen challenge: Contributions made by mast cells, non-mast cells and IL-1 Peer-reviewed

    Xue Deng, Xia Wu, Zhiqian Yu, Iwao Arai, Takashi Sasano, Shunji Sugawara, Yasuo Endo

    INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY　144　(1)　69-78　2007

    DOI： 10.1159/000102617 　

    ISSN： 1018-2438

  95. 細胞外カルシウムのマクロファージ様細胞が持つ潜在的骨形成能促進効果

    本田 義知, 穴田 貴久, 鎌倉 慎治, 中村 雅典, 菅原 俊二, 鈴木 治

    Journal of Oral Biosciences　48　(Suppl.)　160-160　2006/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  96. Erratum to "Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line" [Biochem. Biophys. Res. Commun. 345 (2006) 1155-1160] (DOI:10.1016/j.bbrc.2006.05.013) Peer-reviewed

    Yoshitomo Honda, Takahisa Anada, Shinji Kamakura, Masanori Nakamura, Shunji Sugawara, Osamu Suzuki

    Biochemical and Biophysical Research Communications　347　(3)　843　2006/09/01

    DOI： 10.1016/j.bbrc.2006.06.124 　

    ISSN： 0006-291X 1090-2104

    eISSN： 1090-2104

  97. Inflammatory effect of cleaved bovine lactoferrin by elastase on staphylococcal mastitis Peer-reviewed

    Yumiko Komine, Toshinobu Kuroishi, Jin Kobayashi, Hisashi Aso, Yoshiaki Obara, Katsuo Kumagai, Shunji Sugawara, Ken-Ichi Komine

    JOURNAL OF VETERINARY MEDICAL SCIENCE　68　(7)　715-723　2006/07

    DOI： 10.1292/jvms.68.715 　

    ISSN： 0916-7250

  98. Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line Peer-reviewed

    Y Honda, T Anada, S Kamakura, M Nakamura, S Sugawara, O Suzuki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　345　(3)　1155-1160　2006/07

    DOI： 10.1016/j.bbrc.2006.05.013 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  99. Toll-like receptors, NOD1, and NOD2 in oral epithelial cells Peer-reviewed

    Y. Sugawara, A. Uehara, Y. Fujimoto, S. Kusumoto, K. Fukase, K. Shibata, S. Sugawara, T. Sasano, H. Takada

    JOURNAL OF DENTAL RESEARCH　85　(6)　524-529　2006/06

    DOI： 10.1177/154405910608500609 　

    ISSN： 0022-0345

  100. Mutual augmentation of the induction of the histamine-forming enzyme, histidine decarboxylase, between alendronate and immuno-stimulants (IL-1, TNF, and LPS), and its prevention by clodronate Peer-reviewed

    Deng, X, ZQ Yu, H Funayama, N Shoji, T Sasano, Y Iwakura, S Sugawara, Y Endo

    TOXICOLOGY AND APPLIED PHARMACOLOGY　213　(1)　64-73　2006/05

    DOI： 10.1016/j.taap.2005.09.005 　

    ISSN： 0041-008X

  101. Involvement of Kupffer cells in lipopolysaccharide-induced rapid accumulation of platelets in the liver and the ensuing anaphylaxis-like shock in mice. International-journal

    Kouji Yamaguchi, Zhiqian Yu, Hiroyuki Kumamoto, Yumiko Sugawara, Hiroshi Kawamura, Haruhiko Takada, Takashi Yokochi, Shunji Sugawara, Yasuo Endo

    Biochimica et biophysica acta　1762　(3)　269-75　2006/03

    ISSN： 0006-3002

    More details Close

    Intravenous injection of Klebsiella O3 lipopolysaccharide (LPS) into BALB/c mice induces an anaphylaxis-like shock within minutes. Using 5-hydroxytryptamine as a marker for platelets, we previously suggested that a rapid platelet accumulation in the liver and lung precedes the shock, and that a complement-dependent platelet-degradation is involved in the shock. Here, we examined (i) the effect of platelet-depletion (using an anti-platelet monoclonal antibody) on the shock and (ii) the contribution of macrophages to the platelet-accumulation in those organs. LPS-induced platelet-accumulations in the liver and lung were confirmed by immunostaining. In platelet-depleted mice, the shock was largely prevented. The number of F4/80-positive macrophages was much greater in liver than in lung, and the hepatic macrophages were largely lost in mice given clodronate-encapsulated liposomes. In mice treated with such liposomes, both the LPS-induced accumulation of platelets in the liver (but not in the lung) and the shock were largely prevented, and repopulation of hepatic macrophages restored these LPS-induced responses. These results suggest that (i) platelets are indeed involved in the shock, (ii) Kupffer cells mediate the hepatic platelet accumulation, and (iii) preventing this hepatic accumulation can largely prevent rapid shock being induced by LPS (at the dose used here).

  102. Involvement of Kupffer cells in lipopolysaccharide-induced rapid accumulation of platelets in the liver and the ensuing anaphylaxis-like shock in mice Peer-reviewed

    Kouji Yamaguchi, Zhiqian Yu, Hiroyuki Kumamoto, Yumiko Sugawara, Hiroshi Kawamura, Haruhiko Takada, Takashi Yokochi, Shunji Sugawara, Yasuo Endo

    Biochimica et Biophysica Acta - Molecular Basis of Disease　1762　(3)　269-275　2006/03

    DOI： 10.1016/j.bbadis.2005.11.010 　

    ISSN： 0925-4439

  103. Synergistic Effect of Nod1 and Nod2 Agonists with Toll-Like Receptor Agonists on Human Dendritic Cells To Generate Interleukin-12 and T Helper Type 1 Cells Peer-reviewed

    Tada H, Aiba S, Shibata K, Ohteki T, Takada H

    Infection and Immunity　73　(12)　7967-7976　2005/12

    DOI： 10.1128/iai.73.12.7967-7976.2005 　

    ISSN： 0019-9567

    eISSN： 1098-5522

  104. Arginine-specific gingipains from Porphyromonas gingivalis stimulate production of hepatocyte growth factor (scatter factor) through protease-activated receptors in human gingival fibroblasts in culture. Peer-reviewed

    Uehara A, Muramoto K, Imamura T, Nakayama K, Potempa J, Travis J, Sugawara S, Takada H

    Journal of immunology (Baltimore, Md. : 1950)　175　(9)　6076-6084　2005/11

    ISSN： 0022-1767

  105. Involvement of neutrophil recruitment and protease-activated receptor 2 activation in the induction of IL-18 in mice Peer-reviewed

    K Ikawa, T Nishioka, ZQ Yu, Y Sugawara, J Kawagoe, T Takizawa, Primo, V, B Nikolic, T Kuroishi, T Sasano, H Shimauchi, H Takada, Y Endo, S Sugawara

    JOURNAL OF LEUKOCYTE BIOLOGY　78　(5)　1118-1126　2005/11

    DOI： 10.1189/jlb.0305151 　

    ISSN： 0741-5400

  106. Upregulation of PGRPs by chemically synthesized pathogen-associated molecular patterns via Toll-like receptors, NOD1 and NOD2 in oral epithelial cells. Invited

    Uehara, A, Sugawara, Y, Kurata, S, Fujimoto, Y, Fukase, K, Kusumoto, S, Sasano, T, Shibata, K, Sugawara, S, Takada, H

    International Congress Series　1284　163-168　2005/10

    DOI： 10.1016/j.ics.2005.06.032 　

  107. Comparative appraisal of clodronate, aspirin and dexamethasone as agents reducing alendronate-induced inflammation in a murine model Peer-reviewed

    ZQ Yu, H Funayama, Deng, X, T Kuroishi, T Sasano, S Sugawara, Y Endo

    BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY　97　(4)　222-229　2005/10

    DOI： 10.1111/j.1742-7843.2005.pto_138.x 　

    ISSN： 1742-7835

  108. 培養系ならびに組織内でのヒト歯肉上皮細胞のToll-like receptor系およびNOD系分子の発現

    菅原 由美子, 上原 亜希子, 菅原 俊二, 笹野 高嗣, 高田 春比古

    Journal of Oral Biosciences　47　(Suppl.)　144-144　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  109. Endogenous membrane-bound IL-15 sustains recruitment of IL-2Rβ and common γ through activation of NF-κB in human gingival fibroblasts Peer-reviewed

    Akiko Ozawa, Hiroyuki Tada, Yumiko Sugawara, Akiko Uehara, Takashi Sasano, Hidetoshi Shimauchi, Haruhiko Takada, Shunji Sugawara

    International Congress Series　1284　175-180　2005/09

    DOI： 10.1016/j.ics.2005.06.024 　

    ISSN： 0531-5131

  110. Inhibition of inflammatory and bone-resorption-inhibitory effects of alendronate by etidronate Peer-reviewed

    H Funayama, M Ohsako, Y Monma, H Mayanagi, S Sugawara, Y Endo

    CALCIFIED TISSUE INTERNATIONAL　76　(6)　448-457　2005/06

    DOI： 10.1007/s00223-004-0180-3 　

    ISSN： 0171-967X

  111. Chemically synthesized pathogen-associated molecular patterns increase the expression of peptidoglycan recognition proteins via Toll-like receptors, NOD1 and NOD2 in human oral epithelial cells. Peer-reviewed

    Uehara, A, Sugawara, Y, Kurata, S, Fujimoto, Y, Fukase, K, Kusumoto, S, Satta, Y, Sasano, T, Sugawara, S, Takada, H

    Cell Microbiol.　7　(5)　675-686　2005/05

    DOI： 10.1111/j.1462-5822.2004.00500.x 　

  112. Critical roles of platelets in lipopolysaccharide-induced lethality: effects of glycyrrhizin and possible strategy for acute respiratory distress syndrome Peer-reviewed

    ZQ Yu, Y Ohtaki, KZ Kai, T Sasano, H Shimauchi, T Yokochi, H Takada, S Sugawara, K Kumagai, Y Endo

    INTERNATIONAL IMMUNOPHARMACOLOGY　5　(3)　571-580　2005/03

    DOI： 10.1016/j.intimp.2004.11.004 　

    ISSN： 1567-5769

  113. In vivoにおけるprotease-activate receptor-2(PAR-2)を介するIL-18産生制御

    伊川 桂次, 西岡 貴史, 菅原 由美子, 笹野 高嗣, 島内 英俊, 高田 春比古, 遠藤 康男, 菅原 俊二

    日本免疫学会総会・学術集会記録　34　58-58　2004/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  114. LPSによるマウス肝臓への即時性血小板集積反応 クッパー細胞の関与

    山口 晃史, 熊本 裕行, 川村 仁, 高田 春比古, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　46　(5)　389-389　2004/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  115. Augmentation of Actinobacillus actinomycetemcomitans invasion of human oral epithelial cells and up-regulation of interleukin-8 production by saliva CD14 Peer-reviewed

    A Takayama, A Satoh, T Ngai, T Nishimura, K Ikawa, T Matsuyama, H Shimauchi, H Takada, S Sugawara

    INFECTION AND IMMUNITY　71　(10)　5598-5604　2003/10

    DOI： 10.1128/IAI.71.10.5598-5604.2003 　

    ISSN： 0019-9567

  116. Proteolysis of ICAM-1 on human oral epithelial cells by gingipains Peer-reviewed

    H Tada, S Sugawara, E Nemoto, T Imamura, J Potempa, J Travis, H Shimauchi, H Takada

    JOURNAL OF DENTAL RESEARCH　82　(10)　796-801　2003/10

    ISSN： 0022-0345

  117. Expression of IL-2 receptor beta and gamma chains by human gingival fibroblasts and up-regulation of adhesion to neutrophils in response to IL-2 Peer-reviewed

    A Ozawa, H Tada, R Tamai, A Uehara, K Watanabe, T Yamaguchi, H Shimauchi, H Takada, S Sugawara

    JOURNAL OF LEUKOCYTE BIOLOGY　74　(3)　352-359　2003/09

    DOI： 10.1186/jlb.0103044 　

    ISSN： 0741-5400

  118. Porphyromonas gingivalisジンジパインはヒト歯肉線維芽細胞CD14を分解してLPS不応答性を誘導する

    多田 浩之, 菅原 俊二, 今村 隆寿, 島内 英俊, 高田 春比古, 根本 英二, 高橋 信博

    日本細菌学雑誌　58　(1)　158-158　2003/02

    Publisher: 日本細菌学会

    ISSN： 0021-4930

    eISSN： 1882-4110

  119. Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14/Toll-like receptor system Peer-reviewed

    J Hatakeyama, R Tamai, A Sugiyama, S Akashi, S Sugawara, H Takada

    ORAL MICROBIOLOGY AND IMMUNOLOGY　18　(1)　14-23　2003/02

    DOI： 10.1034/j.1399-302X.2003.180103.x 　

    ISSN： 0902-0055

  120. Synergistic effects of lipopolysaccharide and interferon-gamma in inducing interleukin-8 production in human monocytic THP-1 cells is accompanied by up-regulation of CD14, Toll-like receptor 4, MD-2 and MyD88 expression Peer-reviewed

    R Tamai, S Sugawara, O Takeuchi, S Akira, H Takada

    JOURNAL OF ENDOTOXIN RESEARCH　9　(3)　145-153　2003

    DOI： 10.1179/096805103125001540 　

    ISSN： 0968-0519

  121. Decreased IL-10 production by psoriatic peripheral blood mononuclear cells stimulated with streptococcal superantigen Peer-reviewed

    S Aiba, Z Uddin, S Nakagawa, S Sugawara, H Rikiishi, K Kumagai, H Tagami

    EXPERIMENTAL DERMATOLOGY　11　(4)　337-343　2002/08

    DOI： 10.1034/j.1600-0625.2002.110407.x 　

    ISSN： 0906-6705

  122. Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production Peer-reviewed

    H Tada, S Sugawara, E Nemoto, N Takahashi, T Imamura, J Potempa, J Travis, H Shimauchi, H Takada

    INFECTION AND IMMUNITY　70　(6)　3304-3307　2002/06

    DOI： 10.1128/IAI.70.6.3304-3307.2002 　

    ISSN： 0019-9567

  123. Human gingival CD14(+) fibroblasts primed with gamma interferon increase production of interleukin-8 in response to lipopolysaccharide through up-regulation of membrane CD14 and MyD88 mRNA expression Peer-reviewed

    R Tamai, T Sakuta, K Matsushita, M Torii, O Takeuchi, S Akira, S Akashi, T Espevik, S Sugawara, H Takada

    INFECTION AND IMMUNITY　70　(3)　1272-1278　2002/03

    DOI： 10.1128/IAI.70.1272-1278.2002 　

    ISSN： 0019-9567

  124. ヒト歯肉線維芽細胞膜上のCD26/dipeptidyl peptidase IV —サイトカインおよび菌体成分による発現増強— Peer-reviewed

    根本英二, 菅原俊二, 高田春比古, 庄司 茂, 堀内 博

    日本炎症学会雑誌　20　(1)　13-20　2002

  125. Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1 Peer-reviewed

    A Sugiyama, A Uehara, K Iki, K Matsushita, R Nakamura, T Ogawa, S Sugawara, H Takada

    JOURNAL OF MEDICAL MICROBIOLOGY　51　(1)　27-33　2002/01

    ISSN： 0022-2615

  126. Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14-and Toll-like receptor 4-dependent manner Peer-reviewed

    H Tada, E Nemoto, H Shimauchi, T Watanabe, T Mikami, T Matsumoto, N Ohno, H Tamura, K Shibata, S Akashi, K Miyake, S Sugawara, H Takada

    MICROBIOLOGY AND IMMUNOLOGY　46　(7)　503-512　2002

    DOI： 10.1111/j.1348-0421.2002.tb02727.x 　

    ISSN： 0385-5600

  127. Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells Peer-reviewed

    S Sugawara, A Uehara, T Nochi, T Yamaguchi, H Ueda, A Sugiyama, K Hanzawa, K Kumagai, H Okamura, H Takada

    JOURNAL OF IMMUNOLOGY　167　(11)　6568-6575　2001/12

    ISSN： 0022-1767

  128. Monocytic cell activation by nonendotoxic glycoprotein from Prevotella intermedia ATCC 25611 is mediated by toll-like receptor 2 Peer-reviewed

    S Sugawara, S Yang, K Iki, J Hatakeyama, R Tamai, O Takeuchi, S Akashi, T Espevik, S Akira, H Takada

    INFECTION AND IMMUNITY　69　(8)　4951-4957　2001/08

    DOI： 10.1128/IAI.69.8.4951-4957.2001 　

    ISSN： 0019-9567

  129. Micrococcus luteus teichuronic acids activate human and murine monocytic cells in a CD14-and toll-like receptor 4-dependent manner Peer-reviewed

    SH Yang, S Sugawara, T Monodane, M Nishijima, Y Adachi, S Akashi, K Miyake, S Hase, H Takada

    INFECTION AND IMMUNITY　69　(4)　2025-2030　2001/04

    DOI： 10.1128/IAI.69.4.2025-2030.2001 　

    ISSN： 0019-9567

  130. Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture Peer-reviewed

    SH Yang, R Tamai, S Akashi, O Takeuchi, S Akira, S Sugawara, H Takada

    INFECTION AND IMMUNITY　69　(4)　2045-2053　2001/04

    DOI： 10.1128/IAI.69.4.2045-2053.2001 　

    ISSN： 0019-9567

  131. Cleavage of CD14 on human gingival fibroblasts cocultured with activated neutrophils is mediated by human leukocyte elastase resulting in down-regulation of lipopolysaccharide-induced IL-8 production. Peer-reviewed

    Nemoto E, Sugawara S, Tada H, Takada H, Shimauchi H, Horiuchi H

    J Immunol　165　(10)　5807-5813　2000/11/15

  132. Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness. Peer-reviewed

    Sugawara S, Nemoto E, Tada H, Miyake K, Imamura T, Takada H

    J Immunol　165　(1)　411-418　2000/07/01

  133. Increase of CD26/dipeptidyl peptidase IV expression on human gingival fibroblasts upon stimulation with cytokines and bacterial components. Peer-reviewed

    Nemoto E, Sugawara S, Takada H, Shoji S, Horiuch H

    Infect Immun　67　(12)　6225-6233　1999/12

  134. Lipopolysaccharide-dependent down-regulation of CD27 expression on T cells activated with superantigen Peer-reviewed

    K Kai, H Rikiishi, S Sugawara, M Takahashi, H Takada, K Kumagai

    IMMUNOLOGY　98　(2)　289-295　1999/10

    DOI： 10.1046/j.1365-2567.1999.00857.x 　

    ISSN： 0019-2805

  135. Enhancement by galactosamine of lipopolysaccharide(LPS)-induced tumour necrosis factor production and lethality: its suppression by LPS pretreatment. Peer-reviewed

    Endo Y, Shibazaki M, Yamaguchi K, Kai K, Sugawara S, Takada H, Kikuchi H, Kumagai K

    Br J Pharmacol　128　(1)　5-12　1999/09

    Publisher: Wiley

    DOI： 10.1038/sj.bjp.0702747 　

    ISSN： 0007-1188

  136. Contrasting effects of an aminobisphosphonate, a potent inhibitor of bone resorption, on lipopolysaccharide-induced production of interleukin-1 and tumour necrosis factor alpha in mice. Peer-reviewed

    Sugawara S, Shibazaki M, Takada H, Kosugi H, Endo Y

    Br J Pharmacol　125　(4)　735-740　1998/10

    Publisher: Wiley

    DOI： 10.1038/sj.bjp.0702151 　

    ISSN： 0007-1188

  137. Heterogeneous expression and release of CD14 by human gingival fibroblasts: Characterization and CD14-mediated interleukin-8 secretion in response to lipopolysaccharide. Peer-reviewed

    Sugawara S, A. Sugiyama, E. Nemoto, T. Rikiishi, H. Takada

    Infect. Immun　66　(7)　3043-3049　1998/07

  138. Superantigenicity of helper T-cell mitogen (SPM-2) isolated from culture supernatants of Streptococcus pyogenes Peer-reviewed

    H Rikiishi, S Okamoto, S Sugawara, K Tamura, ZX Liu, K Kumagai

    IMMUNOLOGY　91　(3)　406-413　1997/07

    DOI： 10.1046/j.1365-2567.1997.00277.x 　

    ISSN： 0019-2805

  139. Isolation of a new superantigen with potent mitogenic activity to murine T cells from Streptococcus pyogenes. Peer-reviewed

    Nemoto E, Rikiishi H, Sugawara S, Okamo

    FEMS immunology and medical microbiology　15　(2/3)　81-91　1996/09

    DOI： 10.1016/0928-8244(96)00044-2 　

    ISSN： 0928-8244

  140. SUPERANTIGENS AND IMMUNOLOGICAL DISEASES

    Sugawara Shunji, Kumagai Katsuo

    Japanese Journal of Allergology　45　(5)　435-441　1996

    Publisher: Japanese Society of Allergology

    DOI： 10.15036/arerugi.45.435 　

    ISSN： 0021-4884

  141. Suppression of Stress Protein GRP78 Induction in Tumor B/C10ME Eliminates Resistance to Cell Mediated Cytotoxicity Peer-reviewed

    Shunji Sugawara, Kazuyoshi Takeda, Amy Lee, Gunther Dennert

    Cancer Research　53　(24)　6001-6005　1993/12

    ISSN： 0008-5472

    eISSN： 1538-7445

  142. CTX-B inhibits CTL cytotoxicity and cytoskeletal movements Peer-reviewed

    Shunji Sugawara, Harvey R. Kaslow, Gunther Dennert

    Immunopharmacology　26　(2)　93-104　1993

    DOI： 10.1016/0162-3109(93)90001-7 　

    ISSN： 0162-3109

  143. Nicotinamide and 3-aminobenzamide interfere with receptor-mediated transmembrane signaling in murine cytotoxic T cells: Independence of Golgi reorientation from calcium mobilization and inositol phosphate generation Peer-reviewed

    Marek Nowicki, Carol Landon, Shunji Sugawara, Gunther Dennert

    Cellular Immunology　132　(1)　115-126　1991/01

    DOI： 10.1016/0008-8749(91)90011-Y 　

    ISSN： 0008-8749

    eISSN： 1090-2163

  144. Differential effects of protein synthesis inhibition on CTL and targets in cell-mediated cytotoxicity Peer-reviewed

    Carol Landon, Marek Nowicki, Shunji Sugawara, Gunther Dennert

    Cellular Immunology　128　(2)　412-426　1990/07

    DOI： 10.1016/0008-8749(90)90037-R 　

    ISSN： 0008-8749

    eISSN： 1090-2163

  145. Evidence for differentiation of NK1+ cells into cytotoxic T cells during acute rejection of allogeneic bone marrow grafts Peer-reviewed

    Gunther Dennert, Christian Knobloch, Shunji Sugawara, Boris Yankelevich

    Immunogenetics　31　(3)　161-168　1990/03

    DOI： 10.1007/BF00211551 　

    ISSN： 0093-7711

    eISSN： 1432-1211

  146. Effects of stress on lysability of tumor targets by cytotoxic T cells and tumor necrosis factor Peer-reviewed

    S. Sugawara, M. Nowicki, S. Xie, H. J. Song, G. Dennert

    Journal of Immunology　145　(6)　1991-1998　1990

    ISSN： 0022-1767

  147. NOD mice with high incidence of type 1 diabetes are not T lymphocytopenic.

    SATOH JO, SHINTANI SHIGEKI, NOBUNAGA TOSHIMA, SUGAWARA SHUNJI, MAKINO SUSUMU, TOYOTA TAKAYOSHI, GOTO YOSHIO

    Tohoku J. Exp. Med.　155　(2)　151-158　1988

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.155.151 　

    ISSN： 0040-8727

    More details Close

    SATOH, J., SHINTANI, S., NOBUNAGA, T., SUGAWARA, S., MAKINO, S., TOYOTA, T. and GOTO, Y. NOD Mice with High Incidence of Type 1 Diabetes are not T Lymphocytopenic. Tohoku J. exp. Med., 1988, 155 (2), 151-158 - An autoimmune pathogenesis has been indicated in insulin-dependent (type 1) diabetes mellitus (IDDM). Previously we reported that non-obese diabetic (NOD) mice as an animal model of spontaneously developing IDDM were immunologically characterized by T lymphocytopenia and impaired cellular immunities. The cumulative incidence of diabetes in the T lymphocytopenic female NOD mice was 10-20% by 24 weeks of age. On the other hand, the incidence of diabetes are 80-90% in the female NOD/Shi-Sendai (S), in whom proportion of lymophocyte subsets has not been known yet. Therefore, we examined the spleen cells of female NOD/ Shi-S and female NOD/Shi with high incidence of diabetes, and of female Jcl: ICR as a control. Cell numbers, populations of T cells (Thy 1.2+, Lyt-1+ and Lyt-2+), B cells (surface-Ig+), NK cells (acialo GM1+) and responsiveness to Concanavalin A were analyzed as immunological parameters. In contrast to the T lymphocytopenic NOD, these immunological parameters were not impaired in the NOD/Shi-S and NOD/Shi in comparison to those of Jcl: ICR. The results indicate that there may be a positive association between the incidence of diabetes and T cell number and functions in female NOD mice.

  148. Biotin status affects nickel allergy via regulation of interleukin-1β production in mice Peer-reviewed

    Kuroishi T, Kinbara M, Sato N, Tanaka Y, Nagai Y, Iwakura Y, Endo Y, Sugawara S

    Journal of Nutrition　139　(5)　1031-1036

    DOI： 10.3945/jn.108.097543 　

  149. Muramyldipeptide augments the actions of lipopolysaccharide in mice by stimulating macrophages to produce pro-IL-1β and by down-regulation of the suppressor of cytokine signaling 1 (SOCS1) Peer-reviewed

    Shikama Y, Kuroishi T, Nagai Y, Iwakura Y, Shimauchi H, Takada H, Sugawara S, Endo Y

    Innate Immunity　17　(1)　3-15

    DOI： 10.1177/1753425909347508 　

Show all ︎Show first 5

Misc. 203

  1. Fusobacterium nucleatum感染によるマスト細胞からの細胞外トラップ産生と炎症誘導

    多田浩之, 西岡貴志, 松下健二, 菅原俊二

    第61回歯科基礎医学会学術大会　2019　2019/10

    ISSN： 2187-9109

  2. Porphyromonas gingivalisジンジパインによりマスト細胞が産生するIL-31は、歯肉上皮細胞のclaudin-1発現を抑制しバリア破綻を誘導する

    多田浩之, 西岡貴志, 沼崎研人, 根本英二, 松下健二, 菅原俊二

    第73回日本細菌学会東北支部会　2019/08

  3. ゾレドロネート静脈内投与マウスでのLPSによるIL-1αおよびIL-1βの増加に関してのクロドロネートによる抑制

    鈴木 飛佳理, 坂東 加南, 木山 朋美, 大泉 丈史, 多田 浩之, 遠藤 康男, 菅原 俊二, 高橋 哲

    日本口腔科学会雑誌　68　(2)　147-147　2019/07

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

  4. Zoledronate(bisphosphonate)静脈投与マウスでのLPSによるIL-1産生増強とclodronate(bisphosphonate)による抑制

    鈴木 飛佳理, 坂東 加南, 多田 浩之, 木山 朋美, 大泉 丈史, 船山 ひろみ, 菅原 俊二, 高橋 哲, 遠藤 康夫

    Journal of Oral Biosciences Supplement　2018　429-429　2018/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  5. 筋機能時における好中球由来IL1βの役割

    土谷 昌広, チャウィワンナコン・チャヤニ, 佐々木 啓一, 菅原 俊二, 渡邉 誠, 遠藤 康男

    Journal of Oral Biosciences Supplement　2018　366-366　2018/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  6. P.gingivalis感染によりマスト細胞から産生されたIL‐31はclaudin‐1発現抑制を介して歯肉上皮バリア破綻を誘導する

    多田浩之, 沼崎研人, 西岡貴志, 松下健二, 菅原俊二

    Journal of Oral Biosciences Supplement (Web)　2018　ROMBUNNO.O3‐13 (WEB ONLY)　2018

    ISSN： 2187-9109

  7. 【経皮感作と腸管免疫寛容】 CXCL4は新規ニッケル結合蛋白質であり、ニッケルアレルギーを増強する

    黒石 智誠, 菅原 俊二

    臨床免疫・アレルギー科　68　(5)　508-514　2017/11

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  8. 細胞外purine nucleotide刺激はヒト口腔上皮細胞における炎症性サイトカイン産生を増強する

    宍戸 香, 黒石 智誠, 菅原 俊二

    Journal of Oral Biosciences Supplement　2017　335-335　2017/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  9. 舌下免疫療法による食物アレルギー予防効果の解析

    秋山 なつみ, 桃北 萌子, 宍戸 香, 黒石 智誠, 菅原 俊二

    Journal of Oral Biosciences Supplement　2017　401-401　2017/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  10. Neutrophil extracellular trapsによるヒト血管内皮細胞のDel-1産生抑制

    多田 浩之, 西岡貴志, 松下 健二, 菅原 俊二

    Journal of Oral Biosciences Supplement　2017　511-511　2017/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  11. Neutrophil extracellular trapsによるヒト血管内皮細胞のDel-1産生抑制

    多田浩之, 西岡貴志, 松下健二, 菅原俊二

    Journal of Oral Biosciences Supplement (Web)　2017　2017

    ISSN： 2187-9109

  12. CXCL4は新規Ni結合タンパク質でありNiアレルギーを増強する

    黒石 智誠, 田中 志典, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences Supplement　2016　169-169　2016/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  13. ヒト唾液腺細胞はATP刺激によりIL-6を産生する

    根本 恭利, 黒石 智誠, 菅原 俊二

    Journal of Oral Biosciences Supplement　2015　544-544　2015/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  14. 窒素含有bisphosphonates(N-BPs)の炎症壊死作用のLPSによる増強

    鈴木 飛佳理, 島 和弘, 山口 晃史, 大泉 丈史, 菅原 俊二, 高橋 哲, 遠藤 康男

    Clinical Calcium　25　(5)　745-746　2015/04

    Publisher: (株)医薬ジャーナル社

    ISSN： 0917-5857

  15. ビオチン欠乏に伴うアミノ酸代謝異常と抗酸化能の低下

    黒石 智誠, 菅原 俊二

    ビタミン　89　(4)　237-237　2015/04

    Publisher: (公社)日本ビタミン学会

    ISSN： 0006-386X

  16. BRONJ(bisphosphonate-related osteonecrosis of the jaw)の治療 etidronate置換療法の試み

    大泉 丈史, 山口 晃史, 鈴木 飛佳理, 土谷 昌広, 菅原 俊二, 高橋 哲, 遠藤 康男

    Clinical Calcium　25　(5)　748-748　2015/04

    Publisher: (株)医薬ジャーナル社

    ISSN： 0917-5857

  17. リン酸トランスポーターSLC20/34阻害薬はマウスBRONJ(bisphosphonate-related osteonecrosis of the jaw)を抑制する

    木山 朋美, 土谷 昌広, 佐々木 啓一, 菅原 俊二, 河井 俊久, 遠藤 康男

    Clinical Calcium　25　(5)　746-746　2015/04

    Publisher: (株)医薬ジャーナル社

    ISSN： 0917-5857

  18. IL-33によるヒスチジン脱炭酸酵素の誘導

    坂東加南, 坂東加南, 田中志典, 田中志典, 黒石智誠, 山本照子, 菅原俊二, 遠藤康男

    日本ヒスタミン学会プログラム・講演要旨集　19th　2015

  19. 窒素含有bisphosphonates(N-BPs)の炎症壊死作用 LPSによる増強

    鈴木 飛佳理, 島 和弘, 佐藤 衣莉, 山口 晃史, 大泉 丈史, 菅原 俊二, 高橋 哲, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014　136-136　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  20. Clodronateとetidronate(窒素非含有bisphosphonates)は脊髄神経小胞リン酸トランスポーターSLC17を抑制して鎮痛作用を発揮する

    島 和弘, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014　169-169　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  21. 粉末食長期飼育はマウス糖代謝機構を障害し社会性行動の変化をもたらす

    千葉 航, 土谷 昌広, 渡邉 誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014　147-147　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  22. 窒素含有bisphosphonates(N-BPs)治療患者での顎骨壊死 N-BPsのetidronate(non-N-BP)への置換の試み

    大泉 丈史, 山口 晃史, 鈴木 飛佳理, 土谷 昌広, 菅原 俊二, 高橋 哲, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014　180-180　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  23. N-BPsはalkyl型・heterocyclic型を問わずリン酸トランスポーターSLC20/34を介して細胞内に取り込まれ炎症壊死を起こす

    佐藤 衣莉, 土谷 昌広, 木山 朋美, 大泉 丈史, 山口 晃史, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014　110-110　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  24. 第一世代抗ヒスタミン薬の鎮痛効果

    高橋 萌, 島 和弘, 土谷 昌広, 渡邉 誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014　136-136　2014/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  25. ビオチン欠乏マウスにおける表皮免疫担当細胞の解析

    黒石 智誠, 田中 志典, 遠藤 康男, 菅原 俊二

    ビタミン　88　(4)　247-247　2014/04

    Publisher: (公社)日本ビタミン学会

    ISSN： 0006-386X

  26. 骨吸収抑制作用とは関連しない窒素非含有bisphosphonates(non-N-BPs)(etidronateとclodronate)の鎮痛効果 リン酸トランスポーターSLC17関与の可能性

    島 和弘, 高橋 萌, 山本 照子, 菅原 俊二, 遠藤 康男

    Clinical Calcium　24　(4)　608-609　2014/03

    Publisher: (株)医薬ジャーナル社

    ISSN： 0917-5857

  27. 窒素非含有bisphosphonates(non-N-BPs)の骨吸収抑制作用とは関連しない鎮痛効果 リン酸トランスポーターの関与

    島 和弘, 山本 照子, 菅原 俊二, 遠藤 康男

    東北大学歯学雑誌　32　(2)　65-65　2013/12

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  28. マウス咬筋の持続的活動におけるIL-1の役割

    千葉 航, 米田 博行, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2013　163-163　2013/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  29. Zoledronateの軟組織細胞への取り組み:リン酸transporter関与の可能性

    岡田 諭, 木山 朋美, 大泉 丈史, 佐々木 啓一, 高橋 哲, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2013　135-135　2013/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  30. 窒素含有bisphosphonates(N-BPs)の炎症壊死作用 リン酸transporter阻害剤の効果

    木山 朋美, 岡田 諭, 佐藤 衣莉, 佐々木 啓一, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2013　171-171　2013/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  31. 窒素非含有bisphosphonates(non-N-BPs)の骨吸収抑制作用とは関連しない鎮痛効果 リン酸トランスポーター関与の可能性

    島 和弘, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2013　135-135　2013/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  32. レジンモノマーはアジュバントとして歯科材料アレルゲンよるマウスでのアレルギーを促進する

    坂東 加南, 田中 志典, 黒石 智誠, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2013　164-164　2013/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  33. マウス咬筋長時間活動におけるヒスタミンの役割

    米田 博行, 土谷 昌広, 八百板 富紀枝[新島], 佐々木 啓一, 渡邉 誠, 菅原 俊二, 遠藤 康男

    日本顎口腔機能学会雑誌　20　(1)　42-43　2013/09

    Publisher: 日本顎口腔機能学会

    ISSN： 1340-9085

    eISSN： 1883-986X

  34. リン酸transporterを介するbisphosphonatesの細胞内取り込み

    岡田 諭, 木山 朋美, 大泉 丈史, 佐々木 啓一, 高橋 哲, 菅原 俊二, 遠藤 康男

    Clinical Calcium　23　(4)　600-600　2013/03

    Publisher: (株)医薬ジャーナル社

    ISSN： 0917-5857

  35. Roles played by histamine in strenuous or prolonged masseter muscle activity in mice.

    Hiroyuki Yoneda, Fukie Niijima-Yaoita, Masahiro Tsuchiya, Hiroyuki Kumamoto, Makoto Watanbe, Hiroshi Ohtsu, Kazuhiko Yanai, Takeshi Tadano, Keiichi Sasaki, Shunji Sugawara, Yasuo Endo

    Clin Exp Pharmacol Physiol　40　(12)　848-855　2013

    DOI： 10.1111/1440-1681.12167 　

  36. マウス金属アレルギーへのヒスタミンの関与

    金原 正敬, 黒石 智誠, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2012　110-110　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  37. ヒスタミンによる腫瘍免疫抑制機構

    田中 志典, 黒石 智誠, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences Supplement　2012　111-111　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  38. ニッケル刺激マウス線維芽細胞によるNO産生とIL-1βによるその増強

    黒石 智誠, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences Supplement　2012　146-146　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

  39. マウス咬筋の持続的活動におけるIL-1の役割

    千葉 航, 土谷 昌広, 米田 博行, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2012　110-110　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  40. IL-6はマウス咬筋の激しい活動におけるグルコース維持に関与する

    木山 朋美, 土谷 昌広, 佐々木 啓一, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2012　116-116　2012/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 2187-2333

    eISSN： 2187-9109

  41. マウスにおけるminodronateの骨吸収抑制作用と炎症壊死作用 zoledronateとの比較

    木山 朋美, 坂東 加南, 岡田 諭, 山口 晃史, 金 始瑛, 長谷川 正和, 佐々木 啓一, 菅原 俊二, 遠藤 康男

    Osteoporosis Japan　20　(Suppl.1)　332-332　2012/08

    Publisher: ライフサイエンス出版(株)

    ISSN： 0919-6307

  42. C5a投与によりマウスに誘導されるアナフィラキシー様ショックに対するLPS前投与の効果 好塩基球とヒスタミンの関与

    田中 志典, 黒石 智誠, 遠藤 康男, 菅原 俊二

    補体シンポジウム講演集　49　31-31　2012/08

    Publisher: (一社)日本補体学会

    ISSN： 2185-8470

  43. Effect of introduction of amorphous calcium phosphate on osteoconductivity of octacalcium phosphate bone substitute material

    KOBAYASHI K, ANADA T, HONDA Y, HANDA T, KAMAKURA S, ECHIGO S, SUZUKI O

    The journal of the Japanese Society for Dental Materials and Devices　31　(2)　94-94　2012/03/25

    Publisher: The Japanese Society for Dental Materials and Devices (JSDMD)

    ISSN： 1884-4421

  44. 窒素非含有bisphosphonatesの骨吸収抑制作用とは関連しない鎮痛効果

    岡田諭, 金始瑛, 清流正弘, 山口晃史, 岡田諭, 金始瑛, 清流正弘, 山口晃史, 高橋哲, 山本照子, 菅原俊二, 遠藤康男

    Journal of Oral Biosciences Supplement (Web)　2012　ROMBUNNO.O‐60 (WEB ONLY)　2012

    ISSN： 2187-9109

  45. Roles of IL-6 in Mastication in Mice and Effects of Training and Food Hardness Peer-reviewed

    Masahiro Tsuchiya, Tomomi Kiyama, Shinobu Tsuchiya, Hirohisa Takano, Eiji Nemoto, Keiichi Sasaki, Shunji Sugawara, Yasuo Endo, Makoto Watanabe

    Interface Oral Health Science 2011　104　2012

    Publisher: Springer Nature

    DOI： 10.1007/978-4-431-54070-0_21 　

  46. Analgesic effects of the non-nitrogen-containing bisphosphonates etidronate and clodronate, independent of anti-resorptive effects on bone

    Kim S, Seiryu M, Okada S, Kuroishi T, Takano-Yamamoto T, Sugawara S, Endo Y

    Eur J Pharmacol　2012

    DOI： 10.1016/j.ejphar.2012.11.031 　

  47. マウス長時間噛み砕きにおけるヒスタミンの役割り ブラキシズム・顎関節症の抗ヒスタミン薬による予防・治療を目指す基礎研究

    米田 博行, 土谷 昌広, 渡邉 誠, 佐々木 啓一, 菅原 俊二, 遠藤 康男

    東北大学歯学雑誌　30　(2)　55-55　2011/12

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  48. マウスにおけるminodronateの骨吸収抑制作用と炎症・壊死作用 他のbisphosphonatesとの比較

    木山 朋美, 坂東 加南, 岡田 諭, 山口 晃史, 金 始瑛, 長谷川 正和, 山本 照子, 佐々木 啓一, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　53　(Suppl.)　117-117　2011/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  49. マウスにおけるレジンモノマーのニッケル(Ni)アレルギー促進効果

    坂東 加南, 金原 正敬, 高橋 春江, 米田 博行, 佐々木 啓一, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　53　(Suppl.)　111-111　2011/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  50. ヒト・マウスの種々の細胞におよぼすzoledronateとetidronateのin vitroでの効果

    大泉 丈史, 田中 志典, 大木 亜紀子, 黒石 智誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　53　(Suppl.)　161-161　2011/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  51. マウス長時間噛み砕きにおけるヒスタミンの役割り ブラキシズム・顎関節症の抗ヒスタミン薬による予防・治療を目指す基礎研究

    米田 博行, 土谷 昌広, 佐々木 啓一, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　53　(Suppl.)　122-122　2011/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  52. マウスにおけるminodronateの骨吸収抑制作用と炎症・壊死作用 他のbisphosphonatesとの比較

    坂東 加南, 鈴木 崇弘, 岡田 諭, 大泉 丈史, 山口 晃史, 金 始瑛, 長谷川 正和, 山本 照子, 川村 仁, 菅原 俊二, 遠藤 康男

    Clinical Calcium　21　(5)　757-757　2011/04

    Publisher: (株)医薬ジャーナル社

    ISSN： 0917-5857

  53. マウスにおけるminodronateの骨吸収抑制作用と炎症・壊死作用：他のbisphosphonatesとの比較

    木山朋美, 坂東加南, 岡田諭, 山口晃史, 金始瑛, 長谷川正和, 山本照子, 佐々木啓一, 菅原俊二, 遠藤康男

    歯科基礎　2011

  54. Allergy-inducing nickel concentration is lowered by lipopolysaccharide at both the sensitization and elicitation steps in a murine model

    Kinbara M, Sato N, Kuroishi T, Takano-Yamamoto T, Sugawara S, Endo Y

    Br J Dermatol　2011

    DOI： 10.1111/j.1365-2133.2010.10016.x 　

  55. 骨吸収抑制作用とは関連しないbisphosphonates(BPs)の鎮痛効果

    金始瑛, 清流正弘, 岡田諭, 山本照子, 菅原俊二, 遠藤康男

    歯科基礎　2011

  56. Analysis of antigen incorporating and processing cells in sublingal immunotherapy

    D. Shiraishi, Y. Nagai, Y. Tanaka, Y. Endo, H. Shimauchi, S. Sugawara

    CYTOKINE　52　(1-2)　98-98　2010/10

    DOI： 10.1016/j.cyto.2010.07.417 　

    ISSN： 1043-4666

  57. Histamine reduces susceptibility to NK cells via down-regulation of NKG2D ligand expression on human monocytic leukemia THP-1 cells

    Y. Nagai, Y. Tanaka, R. Sato, T. Kuroishi, S. Sugawara

    CYTOKINE　52　(1-2)　47-47　2010/10

    DOI： 10.1016/j.cyto.2010.07.195 　

    ISSN： 1043-4666

  58. Stimulation of LY-6G on neutrophils in lipopolysaccharide-primed mice induces platelet-activating factor-mediated anaphylaxis-like shock

    Yukinori Tanaka, Yasuhiro Nagai, Toshinobu Kuroishi, Yasuo Endo, Shunji Sugawara

    CYTOKINE　52　(1-2)　25-25　2010/10

    DOI： 10.1016/j.cyto.2010.07.112 　

    ISSN： 1043-4666

  59. Roles of IL-1 and histamine in nickel (Ni) allergy in mice

    Masayuki Kinbara, Yasuhiro Nagai, Teruko Takano-Yamamoto, Yasuo Endo, Shunji Sugawara

    CYTOKINE　52　(1-2)　25-25　2010/10

    DOI： 10.1016/j.cyto.2010.07.111 　

    ISSN： 1043-4666

  60. LPSと抗好中球抗体によりマウスに誘導されるアナフィラキシー様ショック

    田中 志典, 永井 康裕, 黒石 智誠, 遠藤 康男, 菅原 俊二

    補体シンポジウム講演集　47　24-24　2010/09

    Publisher: (一社)日本補体学会

    ISSN： 2185-8470

  61. マウス咬筋疲労へのヒスタミン関与の可能性

    米田 博行, 土谷 昌広, 高藤 康夫, 佐々木 啓一, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　52　(Suppl)　133-133　2010/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  62. 食餌の質的低下はマウスの全身的糖代謝機構を障害する

    土谷 昌広, 佐藤 匡, 土谷 忍, 菅原 俊二, 遠藤 康男, 渡辺 誠

    東北大学歯学雑誌　29　(1)　31-31　2010/06

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  63. Constitutive Expression of a Bacterial Pattern Recognition Receptor, CD14, in Human Salivary Glands and Secretion as a Soluble Form in Saliva (Retraction of vol 10, pg 286, 2003)

    Akiko Uehara, Shunji Sugawara, Kouichi Watanabe, Seishi Echigo, Mitsunobu Sato, Takahiro Yamaguchi, Haruhiko Takada

    CLINICAL AND VACCINE IMMUNOLOGY　17　(4)　698-698　2010/04

    DOI： 10.1128/CVI.00092-10 　

    ISSN： 1556-6811

  64. Neutrophil Serine Proteinases Activate Human Nonepithelial Cells to Produce Inflammatory Cytokines Through Protease-Activated Receptor 2 (Retraction of vol 170, pg 5690, 2003)

    Koji Muramoto, Shunji Sugawara

    JOURNAL OF IMMUNOLOGY　184　(7)　4043-4043　2010/04

    DOI： 10.4049/jimmunol.1090012 　

    ISSN： 0022-1767

  65. Activation of Human Oral Epithelial Cells by Neutrophil Proteinase 3 Through Protease-Activated Receptor-2 (Retraction of vol 169, pg 4594, 2002)

    Shunji Sugawara, Koji Muramoto

    JOURNAL OF IMMUNOLOGY　184　(7)　4042-4042　2010/04

    DOI： 10.4049/jimmunol.1090011 　

    ISSN： 0022-1767

  66. Porphyromonas gingivalis-induced alveolar bone loss in interleukin-48 transgenic mice Peer-reviewed

    Shoji Noriaki, Yoshinaka Kotaro, Nishioka Takashi, Sugawara Yumiko, Sugawara Shunji, Sasano Takashi

    INTERFACE ORAL HEALTH SCIENCE 2009　220-+　2010

    DOI： 10.1007/978-4-431-99644-6_54 　

  67. Binding to bones of nitrogen-containing bisphosphonates(NBPs): effects of non-NBPs

    28　(2)　49-49　2009/12

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  68. LPSと抗好中球抗体によりマウスに誘導されるアナフィラキシー様ショック

    田中 志典, 永井 康裕, 黒石 智誠, 高田 春比古, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　51　(Suppl.)　89-89　2009/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  69. LPSによる炎症反応のMuramyl-dipeptide(MDP)による増強 マクロファージ(Mφ)との関連性

    四釜 洋介, 黒石 智誠, 永井 康裕, 島内 英俊, 高田 春比古, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　51　(Suppl.)　113-113　2009/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  70. ヒト歯肉由来間葉系幹細胞が発現するB7-H3分子による制御性T細胞誘導とその機能解析

    永井 康裕, 黒石 智誠, 白石 大祐, 大木 亜紀子, 菅原 俊二

    Journal of Oral Biosciences　51　(Suppl.)　113-113　2009/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  71. シェーグレン症候群におけるサイトカイン異常

    酒井 梓, 菅原 由美子, 黒石 智誠, 笹野 高嗣, 菅原 俊二

    リウマチ科　42　(2)　211-216　2009/08

    Publisher: (有)科学評論社

    ISSN： 0915-227X

  72. ヒスタミンによるNKレセプターリガンドの表出抑制

    佐藤 隆太郎, 黒石 智誠, 永井 康裕, 越後 成志, 遠藤 康男, 菅原 俊二

    臨床免疫・アレルギー科　51　(6)　640-646　2009/06

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  73. 口腔粘膜の免疫寛容機構と舌下免疫療法

    永井 康裕, 白石 大祐, 黒石 智誠, 大木 亜紀子, 菅原 俊二

    東北大学歯学雑誌　28　(1)　27-27　2009/06

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  74. LPSと好中球によりマウスに誘導されるアナフィラキシー様ショック

    田中 志典, 黒石 智誠, 菅原 俊二, 遠藤 康男

    東北大学歯学雑誌　27　(2)　65-66　2008/12

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  75. シェーグレン症候群の唾液腺におけるIL-18とTh17の関与

    酒井 梓, 菅原 由美子, 黒石 智誠, 笹野 高嗣, 菅原 俊二

    日本口腔粘膜学会雑誌　14　(2)　59-59　2008/12

    Publisher: (一社)日本口腔内科学会

    ISSN： 1341-7983

    eISSN： 1884-1473

  76. K5/IL‐18 Tgマウスにおける唾液腺障害と自己抗体の解析

    佐藤恭子, 黒石智誠, 田中志典, 西岡貴志, 星野友昭, 菅原由美子, 菅原俊二

    日本免疫学会総会・学術集会記録　38　98　2008/11

    ISSN： 0919-1984

  77. LPSと好中球によりマウスに誘導されるアナフィラキシー様ショック

    田中 志典, 黒石 智誠, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　50　(Suppl.)　134-134　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  78. ヒト歯肉線維芽細胞からの間葉系幹細胞の樹立と共刺激分子の発現解析

    永井 康裕, 黒石 智誠, 白石 大祐, 大木 亜希子, 菅原 俊二

    Journal of Oral Biosciences　50　(Suppl.)　155-155　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  79. 歯科用レジンアレルギーモデルマウス作製の試み アレルギー成立におけるH2O2の効果

    高橋 春江, 黒石 智誠, 菅原 俊二, 佐々木 啓一, 遠藤 康男

    Journal of Oral Biosciences　50　(Suppl.)　159-159　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  80. マウスにおけるニッケルアレルギーとその交差反応における金属イオン濃度 LPSの効果

    金原 正敬, 黒石 智誠, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　50　(Suppl.)　206-206　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  81. IL-18 Tgマウスにおける唾液腺の組織学的変化と浸潤リンパ球の解析

    佐藤 恭子, 黒石 智誠, 菅原 由美子, 笹野 高嗣, 菅原 俊二

    日本口腔科学会雑誌　57　(4)　474-475　2008/09

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  82. シェーグレン症候群の唾液腺における病態発現にはIL-18とTh17が関与する

    酒井 梓, 菅原 由美子, 黒石 智誠, 笹野 高嗣, 菅原 俊二

    日本口腔科学会雑誌　57　(4)　475-475　2008/09

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  83. Keratin 5(K5)/IL-18トランスジェニックマウスにおける唾液腺障害の発現と制御性T細胞の関与

    西岡貴志, 黒石 智誠, 菅原 由美子, 田中 志典, 笹野 高嗣, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　50　(Suppl.)　158-158　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  84. IL-18遺伝子導入マウスにおける唾液腺障害と自己抗体の解析

    佐藤 恭子, 黒石 智誠, 田中 志典, 西岡貴志, 菅原 由美子, 菅原 俊二

    Journal of Oral Biosciences　50　(Suppl.)　135-135　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  85. 咀嚼様運動によるマウス咬筋でのIL-6発現とその意義に関する考察

    木山 朋美, 土谷 昌広, 遠藤 康男, 西岡 貴志, 菅原 俊二, 渡辺 誠

    Journal of Oral Biosciences　50　(Suppl.)　175-175　2008/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  86. 咀嚼様運動負荷によるマウス咬筋でのIL-6発現に関する研究

    木山 朋美, 土谷 昌広, 西岡 貴志, 菅原 俊二, 遠藤 康男, 渡辺 誠

    東北大学歯学雑誌　27　(1)　27-27　2008/06

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  87. Biotin deficiency up-regulates tumor necrosis factor-alpha production in murine macrophages

    Toshinobu Kuroishi, Yasuo Endo, Koji Muramoto, Shunji Sugawara

    FASEB JOURNAL　22　2008/04

    ISSN： 0892-6638

  88. IL-18 Tgマウスにおける唾液腺の組織学的変化と自己抗体の解析

    佐藤 恭子, 黒石 智誠, 田中 志典, 伊藤 あゆみ, 西岡貴志, 菅原 由美子, 笹野 高嗣, 菅原 俊二

    日本口腔粘膜学会雑誌　14　(2)　70-70　2008

    Publisher: (一社)日本口腔内科学会

    ISSN： 1341-7983

  89. ニッケルアレルギーの自然免疫を背景とした発症機序

    佐藤直毅, 金原正敬, 高橋春江, 黄玲, 船山ひろみ, 黒石智誠, 山本照子, 佐々木啓一, 高田春比古, 菅原俊二, 遠藤康男

    臨床免疫・アレルギー科　618　2008

  90. 3.窒素含有bisphosphonates (NBPs)の壊死作用 : clodronate (Clo,non-NBP)による抑制とLPSによる増強(一般口演,東北大学創立100周年第51回東北大学歯学会講演抄録,歯学情報)

    大泉 丈史, 山口 晃史, 川村 仁, 菅原 俊二, 遠藤 康男, 東北大・院・歯顎顔面外科:東北大・院・口腔分子制御, 東北大・院・歯顎顔面外科, 東北大・院・歯顎顔面外科, 東北大・院・口腔分子制御, 東北大・院・口腔分子制御

    東北大学歯学雑誌 = Tohoku University dental journal　26　(2)　44-44　2007/12/01

    ISSN： 0287-3915

  91. マウスにおけるニッケルアレルギー 交差反応およびLPSのニッケル濃度におよぼす効果

    金原 正敬, 黒石 智誠, 菅原 俊二, 遠藤 康男

    日本免疫学会総会・学術集会記録　37　101-101　2007/10

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  92. マウスにおけるニッケルアレルギー 感作過程における各種微生物成分および炎症性物質の効果

    高橋 春江, 金原 正敬, 黒石 智誠, 高田 春比古, 菅原 俊二, 遠藤 康男

    日本免疫学会総会・学術集会記録　37　101-101　2007/10

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  93. 骨吸収抑制薬bisphosphonates(BP)の壊死作用 窒素含有BP(NBP)と窒素非含有BP(non-NBP)の作用の違い

    大泉 丈史, 山口 晃史, 船山 ひろみ, 黒石 智誠, 菅原 俊二, 遠藤 康男

    日本免疫学会総会・学術集会記録　37　166-166　2007/10

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  94. Concanavalin A肝炎のLPS前投与による抑制:血小板とマクロファージの関与

    兪 志前, 山口 晃史, Deng Xue, 黒石 智誠, 一石 英一郎, 菅原 俊二, 遠藤 康男

    日本免疫学会総会・学術集会記録　37　190-190　2007/10

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  95. ヒスタミン刺激によるヒト単球様細胞表面NKG2Dリガンド発現の抑制

    佐藤 隆太郎, 黒石 智誠, 遠藤 康夫, 菅原 俊二

    日本免疫学会総会・学術集会記録　37　199-199　2007/10

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  96. K5/IL-18Tgマウスにおける唾液腺浸潤細胞の解析

    佐藤 恭子, 黒石 智誠, 西岡貴志, 菅原 由美子, 星野 友昭, 菅原 俊二

    日本免疫学会総会・学術集会記録　37　266-266　2007/10

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  97. 窒素含有bisphosphonates(NBPs)の壊死作用 clodronate(Clo,non-NBP)による抑制とLPSによる増強

    大泉 丈史, 中目 晴子, 山口 晃史, 川村 仁, 黒石 智誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　49　(Suppl.)　89-89　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  98. ビオチンによる金属アレルギー炎症の制御

    黒石 智誠, 金原 正敬, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　49　(Suppl.)　128-128　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  99. マウスにおける金属アレルギー 交差反応およびLPSのニッケル濃度におよぼす効果

    金原 正敬, 黒石 智誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　49　(Suppl.)　128-128　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  100. ヒスタミンによるヒト単球様細胞におけるNKG2Dリガンド発現の抑制

    佐藤 隆太郎, 黒石 智誠, 越後 成志, 遠藤 康夫, 菅原 俊二

    Journal of Oral Biosciences　49　(Suppl.)　129-129　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  101. 窒素含有bisphosphonates(NBPs)の壊死作用 etidronateのNBPs代用薬としての可能性

    中目 晴子, 大泉 丈史, 船山 ひろみ, 山口 晃史, 川村 仁, 黒石 智誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　49　(Suppl.)　132-132　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  102. シェーグレン症候群病態発現におけるIL-18とIL-17の関与

    酒井 梓, 菅原 由美子, 黒石 智誠, 笹野 高嗣, 菅原 俊二

    日本臨床免疫学会会誌　30　(4)　326-326　2007/08

    Publisher: 日本臨床免疫学会

    DOI： 10.14906/jscisho.35.0.102.0 　

    ISSN： 0911-4300

    eISSN： 1349-7413

  103. Keratin 5(K5)/IL-18トランスジェニックマウスでの唾液腺障害の誘導

    西岡貴志, 黒石 智誠, 菅原 由美子, 笹野 高嗣, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　49　(Suppl.)　159-159　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  104. IL-18Tgマウスにおける唾液腺浸潤リンパ球の解析

    佐藤 恭子, 黒石 智誠, 西岡貴志, 菅原 由美子, 菅原 俊二

    Journal of Oral Biosciences　49　(Suppl.)　128-128　2007/08

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  105. Biotin modulates metal allergy via regulation of IL-1 beta production

    Toshinobu Kuroishi, N. Sato, Y. Endo, S. Sugawara

    INFLAMMATION RESEARCH　56　S411-S412　2007/06

    ISSN： 1023-3830

  106. Functional TLRs and NODs in Human Gingival Fibroblasts

    UEHARA A., TAKADA H.

    J Dent Res　86　(3)　249-254　2007/03/01

    ISSN： 0022-0345

  107. 2.Ni(+LPS)感作マウスでのNiと他金属との交差allergy反応(第49回東北大学歯学会講演抄録,歯学情報)

    金原 正敬, 佐藤 直毅, 木村 幸平, 菅原 俊二, 遠藤 康男, 東北大学歯学部:東北大学大学院歯学研究科・口腔分子制御, 東北大学大学院歯学研究科・口腔分子制御:咬合機能再建, 咬合機能再建, 東北大学大学院歯学研究科・口腔分子制御, 東北大学大学院歯学研究科・口腔分子制御

    東北大学歯学雑誌 = Tohoku University dental journal　25　(2)　87-87　2006/12/01

    ISSN： 0287-3915

  108. 1.窒素含有bisphosphonate(N-BP)の炎症作用のclodronate(C,non-N-BP)による抑制とLPSによる増強 : 機序解明へのBP-line応用の試み(第49回東北大学歯学会講演抄録,歯学情報)

    大泉 丈史, 船山 ひろみ, 山口 晃史, 川村 仁, 菅原 俊二, 遠藤 康男, 東北大学大学院歯学研究科・顎顔面外科:口腔分子制御, 口腔微生物, 東北大学大学院歯学研究科・顎顔面外科, 東北大学大学院歯学研究科・顎顔面外科, 口腔分子制御, 口腔分子制御

    東北大学歯学雑誌 = Tohoku University dental journal　25　(2)　87-87　2006/12/01

    ISSN： 0287-3915

  109. ヒト耳下腺唾液に発現するIL-18の役割

    酒井 梓, 黒石 智誠, 菅原 由美子, 菅原 俊二, 笹野 高嗣

    日本口腔粘膜学会雑誌　12　(2)　107-108　2006/12

    Publisher: (一社)日本口腔内科学会

    ISSN： 1341-7983

    eISSN： 1884-1473

  110. 全身疾患と口腔病変 全身疾患を引き起こす口腔病変 細菌に対する過剰免疫反応 (歯界展望)

    笹野高嗣, 菅原俊二

    歯界展望　108　(5)　1002-1003　2006/11

  111. IgE、マスト細胞とアレルギー 新たな調節因子と治療への応用 マウスにおける金属アレルギー LPSによる増強と交差反応

    金原 正敬, 佐藤 直毅, 黒石 智誠, 菅原 俊二, 遠藤 康男

    日本免疫学会総会・学術集会記録　36　158-158　2006/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  112. アレルギー性炎症の制御メカニズムの解明に向けて 自然免疫によるNiアレルギーの誘導

    佐藤 直毅, 金原 正敬, 黒石 智誠, 岩倉 洋一郎, 菅原 俊二, 遠藤 康男

    日本免疫学会総会・学術集会記録　36　294-294　2006/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  113. Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line (vol 345, pg 1155, 2006)

    Yoshitomo Honda, Takahisa Anada, Shinji Kamakura, Masanori Nakamura, Shunji Sugawara, Osamu Suzuki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　347　(3)　843-843　2006/09

    DOI： 10.1016/j.bbrc.2006.06.124 　

    ISSN： 0006-291X

  114. Ni(+LPS)感作マウスでのNiと他金属との交差allergy反応

    金原 正敬, 佐藤 直毅, 黒石 智誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　48　(Suppl.)　122-122　2006/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  115. LPSは自然免疫およびヒスタミン合成酵素histidine decarboxylaseを介して金属(M)アレルギー(A)を促進する

    佐藤 直毅, 金原 正敬, 黒石 智誠, 木村 幸平, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences　48　(Suppl.)　145-145　2006/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  116. ビオチン欠乏はマクロファージによるTNF-α産生を増強する

    黒石 智誠, 栢島 亜由美, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　48　(Suppl.)　146-146　2006/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  117. 唾液腺の病態発現におけるIL-18の関与

    酒井 梓, 黒石 智誠, 菅原 由美子, 笹野 高嗣, 菅原 俊二

    Journal of Oral Biosciences　48　(Suppl.)　181-181　2006/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  118. ヒト歯肉線維芽細胞におけるヒスタミンの免疫反応の増強

    南 匠, 黒石 智誠, 小澤 亜紀子, 遠藤 康男, 島内 英俊, 菅原 俊二

    Journal of Oral Biosciences　48　(Suppl.)　196-196　2006/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  119. Propionibacterium acnes/LPS処理したマウスのケラチノサイト上皮細胞からの血清IL-18産生誘導．

    西岡貴志, 兪志前, 菅原由美子, 笹野高嗣, 遠藤康男, 菅原俊二

    歯科基礎医学会雑誌　48　(Supplement)　146　2006/09

    ISSN： 1349-0079

  120. Synergistic effects of histamine and inflammatory cytokines on the induction of IL-8 production in human gingival fibroblasts

    MINAMI Takumi, OZAWA Akiko, SUGAWARA Shunji, SHIMAUCHI Hidetoshi

    48　128-128　2006/03/31

    ISSN： 0385-0110

  121. 歯周疾患における唾液中催炎性ラクトフェリンポリペプチドの性状およびその産生機構について

    小澤 亜紀子, 小峯 健一, 黒石 智誠, 南 匠, 菅原 俊二, 島内 英俊

    日本歯周病学会会誌　48　(春季特別)　191-191　2006/03

    Publisher: (NPO)日本歯周病学会

    DOI： 10.14833/amjsp.2006s.0.112.0 　

    ISSN： 0385-0110

  122. 2. Niアレルギー性皮膚炎 : マウス・モデルでの感作過程におけるLPSの効果(一般口演,第47回東北大学歯学会講演抄録)

    佐藤 直毅, 木村 幸平, 菅原 俊二, 遠藤 康男, 東北大学大学院歯学研究科 口腔分子制御:東北大学大学院歯学研究科 咬合機能再建, 東北大学大学院歯学研究科 咬合機能再建, 東北大学大学院歯学研究科 口腔分子制御, 東北大学大学院歯学研究科 口腔分子制御

    東北大学歯学雑誌 = Tohoku University dental journal　24　(2)　68-68　2005/12/27

    ISSN： 0287-3915

  123. 1. Nitrogen-containing bisphosphonates (N-BPs)の炎症性副作用 : 組織IL-1の関与(一般口演,第47回東北大学歯学会講演抄録)

    笹野 高嗣, 菅原 俊二, 遠藤 康男, Xue Deng, 東北大学大学院歯学研究科 分子制御:東北大学大学院歯学研究科 診断, 東北大学大学院歯学研究科 診断, 東北大学大学院歯学研究科 分子制御, 東北大学大学院歯学研究科 分子制御

    東北大学歯学雑誌 = Tohoku University dental journal　24　(2)　68-68　2005/12/27

    ISSN： 0287-3915

  124. 歯周疾患に伴い増加する唾液中催炎性ラクトフェリンポリペプチドの性状とその産生機構

    黒石 智誠, 小峯 健一, 小澤 亜紀子, 南 匠, 島内 英俊, 菅原 俊二

    日本免疫学会総会・学術集会記録　35　183-183　2005/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  125. ヒト唾液腺細胞株におけるIL-18の産生と活性発現に関する解析

    酒井 梓, 黒石 智誠, 菅原 由美子, 菅原 俊二

    日本免疫学会総会・学術集会記録　35　183-183　2005/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  126. 炎症性サイトカイン刺激によるヒト歯肉線維芽細胞からのIL-8産生誘導におけるヒスタミンの相乗効果

    南 匠, 黒石 智誠, 小澤 亜紀子, 遠藤 康男, 島内 英俊, 菅原 俊二

    日本免疫学会総会・学術集会記録　35　184-184　2005/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  127. マウスにおける粘膜細胞からのIL-18誘導における好中球とprotease-activated receptor 2(PAR2)の関与

    西岡貴志, 伊川 桂次, 兪 志前, 菅原 由美子, 遠藤 康男, 菅原 俊二

    日本免疫学会総会・学術集会記録　35　183-183　2005/11

    Publisher: (NPO)日本免疫学会

    ISSN： 0919-1984

  128. ヒト耳下腺唾液および唾液腺細胞におけるIL-18発現の解析

    酒井 梓, 黒石 智誠, 菅原 由美子, 笹野 高嗣, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　97-97　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  129. ヒト歯肉線維芽細胞からのIL-8産生誘導におけるヒスタミンと炎症性サイトカインの相乗効果

    南 匠, 黒石 智誠, 小澤 亜紀子, 遠藤 康男, 島内 英俊, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　99-99　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  130. ヒト耳下腺唾液および唾液腺細胞株におけるToll-Like Receptor 2発現の解析

    黒石 智誠, 酒井 梓, 小峯 健一, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　129-129　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  131. 唾液中催炎性ラクトフェリン・ポリペプチドの産生に関わる酵素と歯周病との関連

    小峯 健一, 黒石 智誠, 小峯 優美子, 小澤 亜紀子, 南 匠, 島内 英俊, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　140-140　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  132. 花粉症罹患者の唾液中催炎性ラクトフェリン・ポリペプチド濃度の動態と歯周病との関連

    高山 敦子, 黒石 智誠, 小澤 亜紀子, 南 匠, 島内 英俊, 小峯 健一, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　140-140　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  133. 歯周病診断指標としての唾液中催炎性ラクトフェリン・ポリペプチドの測定

    小澤 亜紀子, 小峯 健一, 黒石 智誠, 小峯 優美子, 南 匠, 島内 英俊, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　140-140　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  134. ヒト耳下腺唾液および唾液腺細胞におけるIL-18発現の解析

    酒井 梓, 黒石 智誠, 菅原 由美子, 笹野 高嗣, 菅原 俊二

    日本口腔科学会雑誌　54　(4)　542-542　2005/09

    Publisher: (NPO)日本口腔科学会

    ISSN： 0029-0297

    eISSN： 2185-0461

  135. in vivoでの粘膜細胞からのIL-18誘導における好中球とprotease-activated receptor-2(PAR-2)の関与

    西岡貴志, 伊川 桂次, 兪 志前, 菅原 由美子, 笹野 高嗣, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences　47　(Suppl.)　99-99　2005/09

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

    eISSN： 1880-3865

  136. 【情報伝達分子としてのプロテアーゼとそのレセプター】 PAR-2と炎症とのかかわり (Surgery Frontier)

    菅原俊二

    Surgery Frontier　12　(2)　149-154　2005/06

  137. Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized Toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in hum・・・

    Uehara A, Yang S, Fujimoto Y, Fukase K, Kusumoto S, Shibata K, Sugawara S, Takada H

    Cell Microbiol　7　(1)　53-61　2005

    Publisher: Wiley

    DOI： 10.1111/j.1462-5822.2004.00433.x 　

    ISSN： 1462-5814

    eISSN： 1462-5822

    More details Close

    Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized Toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in human monocytic cells in culture.

  138. Host Defense of Oral Mucosa and the Molecular Mechanism of Oral Mucosal Signal Transduction Diseases

    Shunji Sugawara

    Journal of Oral Biosciences　47　(2)　115-125　2005

    DOI： 10.2330/joralbiosci.47.115 　

    ISSN： 1349-0079

  139. Immune functions of proteinase 3

    S Sugawara

    CRITICAL REVIEWS IN IMMUNOLOGY　25　(5)　343-359　2005

    DOI： 10.1615/CritRevImmunol.v25.i5.10 　

    ISSN： 1040-8401

  140. 1. Dexamethasoneおよびpyrilamineのマウス大腿骨Ca量におよぼす効果 : ヒスタミンとの関連性(第45回東北大学歯学会講演抄録)

    〓 雪, 船山 ひろみ, 笹野 高嗣, 菅原 俊二, 遠藤 康男, 東北大学大学院歯学研究 口腔分子制御:東北大学大学院歯学研究 口腔診断, 東北大学大学院歯学研究 口腔分子制御:東北大学大学院歯学研究 口腔微生物, 東北大学大学院歯学研究 口腔診断, 東北大学大学院歯学研究 口腔分子制御, 東北大学大学院歯学研究 口腔分子制御

    東北大学歯学雑誌 = Tohoku University dental journal　23　(2)　88-88　2004/12/30

    ISSN： 0287-3915

  141. Ovalbumin(OVA)感作マウスでのOVA challenge後の組織IL-1βの増加

    佐藤 直毅, Wu Xia, 庄司 憲明, 木村 幸平, 笹野 高嗣, 菅原 俊二, 遠藤 康男

    東北大学歯学雑誌　23　(2)　88-88　2004/12

    Publisher: 東北大学歯学会

    ISSN： 0287-3915

  142. 【自然免疫と疾患】 疾患との関連,治療への応用 自然免疫と歯周病 (医学のあゆみ)

    高田春比古, 菅原俊二

    医学のあゆみ　別冊　(自然免疫と疾患)　99-104　2004/11

  143. サイトカイン処理した口腔上皮細胞はproteinase 3を産生し、抗PR3抗体刺激によりPAR-2およびNF-κB依存的にケモカインを放出する

    上原 亜希子, 菅原 由美子, 高田 春比古, 菅原 俊二

    Journal of oral biosciences　46　(5)　426-426　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  144. 唾液ラクトフェリンポリペプチドの解析と歯周病との関連

    小峯 健一, 横山 敦子, 島内 英俊, 菅原 俊二

    Journal of oral biosciences　46　(5)　434-434　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  145. Protease-activated receptor(PAR)を介する口腔粘膜細胞の炎症・免疫応答

    上原 亜希子, 菅原 俊二

    Journal of oral biosciences　46　(5)　371-371　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  146. ヒト歯肉線維芽細胞における内在性IL-15によるIL-2受容体(IL-2R)発現の制御機構

    小澤 亜紀子, 上原 亜希子, 菅原 由美子, 島内 英俊, 高田 春比古, 菅原 俊二

    Journal of oral biosciences　46　(5)　380-380　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  147. Aminobisphosphonatesの炎症作用とclodronateによる抑制

    トウ 雪, 菅原 俊二, 遠藤 康男

    Journal of oral biosciences　46　(5)　466-466　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  148. マウスへのLPS静脈注射による血小板反応と末梢血流の関係

    大場 麻美, 刈田 啓史郎, 高田 春比古, 菅原 俊二, 遠藤 康男

    Journal of oral biosciences　46　(5)　473-473　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  149. Toll Like receptor(TLR)系ならびにNOD系を介する菌体成分刺激によるヒト口腔上皮細胞のペプチドグリカン認識タンパク発現誘導

    上原 亜希子, 柴田 健一郎, 菅原 俊二, 高田 春比古

    Journal of oral biosciences　46　(5)　478-478　2004/09/01

    Publisher: 歯科基礎医学会

    ISSN： 1349-0079

  150. Protease‐activate receptor‐2(PAR‐2)を介するIL‐18産生制御機構の解析

    伊川桂次, 西岡貴志, 菅原由美子, 笹野高嗣, 島内英俊, 高田春比古, 遠藤康男, 菅原俊二

    J Oral Biosci　46　(5)　391-391　2004/09/01

    Publisher: (一社)歯科基礎医学会

    ISSN： 1349-0079

  151. Adrenalineに対するin vivoにおける血小板の反応.

    兪 志前, 菅原 俊二, 遠藤 康男

    歯科基礎医学会雑誌　46　(5)　473　2004/09

  152. プロテアーゼによる細胞活性化機構と疾患 (細胞)

    菅原俊二, 川越淳一

    細胞　36　(9)　376-379　2004/08

    Publisher: ニュー・サイエンス社

    ISSN： 1346-7557

  153. 1. Alendronate(Aminobisphosphonate)によるIL-1およびTNFの炎症作用の増強とclodronate(non-aminobisphosphonate)による抑制(第44回東北大学歯学会講演抄録)

    〓 雪, 菅原 俊二, 笹野 高嗣, 遠藤 康男, 東北大学大学院歯学研究科 口腔分子制御:東北大学大学院歯学研究科 診断, 東北大学大学院歯学研究科 口腔分子制御, 東北大学大学院歯学研究科 診断, 東北大学大学院歯学研究科 口腔分子制御

    東北大学歯学雑誌 = Tohoku University dental journal　23　(1)　36-36　2004/06/30

    ISSN： 0287-3915

  154. 口腔粘膜の防御機構 (細胞)

    菅原俊二

    細胞　36　(9)　353-356　2004/04

  155. Proinflammatory cytokines induce proteinase 3 as membrane-bound and secretory forms in human oral epithelial cells and antibodies to proteinase 3 activate the cells through protease-activated receptor-2.

    Uehara Akiko, Sugawara Yumiko, Sasano Takashi, Takada Haruhiko, Sugawara Shunji

    J Immunol　173　(6)　4179-4189　2004

  156. Endogenous IL-15 sustains recruitment of IL-2Rbeta and common gamma and IL-2-mediated chemokine production in normal and inflamed human gingival fibroblasts.

    Ozawa Akiko, Tada Hiroyuki, Sugawara Yumiko, Uehara Akiko, Sasano Takashi, Shimauchi Hidetoshi, Takada Haruhiko, Sugawara Shunji

    J Immunol　173　(8)　5180-5188　2004

  157. ヒト歯肉線維芽細胞のIL-2及びIL-15応答性

    小澤 亜紀子, 多田 浩之, 島内 英俊, 高田 春比古, 菅原 俊二

    歯科基礎医学会雑誌　45　(5)　274-274　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  158. 3種の好中球セリンプロテアーゼに対するヒト口腔上皮細胞と歯肉線維芽細胞のPAR2応答性の相違

    上原 亜希子, 高田 春比古, 菅原 俊二

    歯科基礎医学会雑誌　45　(5)　274-274　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  159. ヒト唾液中CD14分子はActinobacillus actinomycetemeomitansのヒト口腔上皮細胞への侵入とIL-8産生を増強する

    高山 敦子, 島内 英俊, 高田 春比古, 菅原 俊二

    歯科基礎医学会雑誌　45　(5)　272-272　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  160. アレルギー反応におけるヒスタミン合成酵素の誘導

    wu xia, 吉田 篤史, 菅原 俊二, 笹野 高嗣, 遠藤 康男

    歯科基礎医学会雑誌　45　(5)　371-371　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  161. Protease-activated receptor-2(PAR-2)によるin vivoでのIL-18産生の調節

    伊川 桂次, 上原 亜希子, 島内 英俊, 高田 春比古, 菅原 俊二

    歯科基礎医学会雑誌　45　(5)　367-367　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  162. 5-Hydroxytriptamine(5HT,セロトニン)による血小板の肺への移行

    大場 麻美, 菅原 俊二, 笹野 高嗣, 遠藤 康男

    歯科基礎医学会雑誌　45　(5)　368-368　2003/09/01

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  163. Proteolysis of ICAM-1 on human oral epithelial cells by cysteine proteinase, (Gingipains) from Porphyromonas gingivalis leading to down-regulation of neutrophil adhesion.

    H. Tada, S. Sugawara, E. Nemoto, N. Takahashi, T. Imamura, J. Potempa, J. Travis, H. Shimauchi, H. Takada

    JOURNAL OF DENTAL RESEARCH　82　B41-B41　2003/06

    ISSN： 0022-0345

  164. PAR(プロテアーゼ活性化受容体)を介した好中球と上皮細胞のクロストーク (感染・炎症・免疫)

    上原亜希子, 菅原俊二

    感染・炎症・免疫　33　(2)　154-156　2003/06

  165. 自然免疫と歯周病 (第1土曜特集 自然免疫と疾患) -- (疾患との関連,治療への応用)

    高田 春比古, 菅原 俊二

    医学のあゆみ　205　(1)　97-102　2003/04/05

    Publisher: 医歯薬出版

    ISSN： 0039-2359

  166. 自然免疫と歯周病 (医学のあゆみ)

    高田春比古, 菅原俊二

    医学のあゆみ　205　(1)　97-102　2003/04

  167. 口腔粘膜における自然免疫と生体防御 (東北大歯誌)

    菅原俊二

    東北大歯誌　22　(1)　11-18　2003/04

  168. Neutrophil serine proteinases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2.

    Uehara Akiko, Muramoto Koji, Takada Haruhiko, Sugawara Shunji

    J Immunol　170　(11)　5690-5696　2003

    DOI： 10.4049/jimmunol.170.11.5690 　

  169. Constitutive expression of a bacterial pattern recognition receptor, CD14, in human salivary glands and secretion as a soluble form in saliva

    Uehara A, Sugawara S, Watanabe K, Echigo S, Sato M, Yamaguchi T, Takeda H

    Clinical and Diagnostic Laboratory Immunology　10　(2)　286-292　2003

    DOI： 10.1128/CDLI.10.2.286-292.2003 　

  170. ヒト唾液中に存在する唾液腺細胞由来の遊離型CD14

    菅原 俊二, 上原 亜希子, 越後 成志, 高田 春比古

    歯科基礎医学会雑誌　44　(5)　459-459　2002/09/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  171. 好中球proteinase 3はPAR2を介して口腔上皮細胞を活性化する

    上原 亜希子, 菅原 俊二, 高田 春比古

    歯科基礎医学会雑誌　44　(5)　406-406　2002/09/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  172. ヒト歯肉線維芽細胞のインターロイキン-2受容体(IL-2R)βならびにγの発現とIL-2応答性

    小澤 亜紀子, 菅原 俊二, 上原 亜希子, 玉井 利代子, 多田 浩之, 島内 英俊, 高田 春比古

    歯科基礎医学会雑誌　44　(5)　406-406　2002/09/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  173. 口腔粘膜とサイトカインネットワーク (炎症と免疫)

    菅原俊二, 高田春比古

    炎症と免疫　10　(3)　221-227　2002/04

  174. Priming of human oral epithelial cells by interferon-gamma to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans.

    Uehara A, Sugawara S, Takada H

    J Med Microbiol　51　(8)　626-634　2002

  175. Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2.

    Uehara Akiko, Sugawara Shunji, Muramoto Koji, Takada Haruhiko

    J Immunol　169　(8)　4594-4603　2002

  176. Innate immune responses in oral mucosa

    S Sugawara, A Uehara, R Tamai, H Takada

    JOURNAL OF ENDOTOXIN RESEARCH　8　(6)　465-468　2002

    DOI： 10.1179/096805102125001082 　

    ISSN： 0968-0519

  177. 好中球proteinase3とLPSとの共刺激によるヒト口腔上皮細胞の活性型インターロイキン(IL)-18産生

    菅原 俊二, 上原 亜希子, 半澤 和雄, 熊谷 勝男, 高田 春比古

    歯科基礎医学会雑誌　43　(5)　530-530　2001/08/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  178. 各種サイトカインで前処理したヒト口腔上皮細胞は菌体成分に応答する

    上原 亜希子, 菅原 俊二, 大工原 恭, 高田 春比古

    歯科基礎医学会雑誌　43　(5)　611-611　2001/08/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  179. Porphyromonas gingivalisのジンジパインによるヒト歯肉線維芽細胞のCD14分子分解とLPS不応答性の誘導

    多田 浩之, 菅原 俊二, 高橋 信博, 島内 英俊, 高田 春比古

    歯科基礎医学会雑誌　43　(5)　614-614　2001/08/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  180. 【自然免疫(innate immunity)における細菌の認識機構 CD14とTLRを中心に】 歯周病とCD14/Toll-like receptor系 (炎症と免疫)

    菅原俊二, 高田春比古

    炎症と免疫　9　(5)　575-581　2001/08

  181. 【インターロイキン18(IL-18) 注目されている新しいサイトカイン】 好中球proteinase3による活性型IL-18の誘導 (侵襲と免疫)

    菅原俊二, 上原亜希子

    侵襲と免疫　10　(2)　53-58　2001/05

  182. LPSとインターフェロンγはヒト単球系THP-1細胞のCD14/Toll-like receptor系を増幅して相乗的にIL-8を誘導する

    玉井利代子, 菅原俊二, 高田春比古

    日本免疫学会総会・学術集会記録　31　2001

    ISSN： 0919-1984

  183. インターフェロンγによるヒト単球系THP-1細胞のCD14/Toll-like receptor系を介するLPS応答の増強

    玉井利代子, 菅原俊二, 高田春比古

    日本細菌学雑誌　56　(1)　2001

    ISSN： 0021-4930

  184. Contrasting responses of human gingival and colonic epithelial cells to lipopolysaccharides, lipoteichoic acids and peptidoglycans in the presence of soluble CD14.

    Uehara A, Sugawara S, Tamai R, Takada H

    Med Microbiol Immunol (Berl)　189　(4)　185-192　2001

    DOI： 10.1007/s004300100063 　

  185. Porphyromonas gingivalisジンジパインのCD14分子分解作用とヒト単球のLPS不応答性の誘導

    菅原 俊二, 多田 浩之, 高田 春比古

    歯科基礎医学会雑誌　42　(5)　414-414　2000/08/30

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  186. ヒト歯根膜細胞ならびに歯肉線維芽細胞のCD14/Toll-like recepterと菌体成分応答

    畠山 純子, 玉井 利代子, 杉山 明子, 菅原 俊二, 高田 春比古

    歯科基礎医学会雑誌　42　(5)　416-416　2000/08/30

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  187. ヒト口腔上皮細胞の各種菌体成分不応答性とシグナル伝達活性化脂質に対する応答性

    上原 亜希子, 玉井 利代子, 菅原 俊二, 高田 春比古

    歯科基礎医学会雑誌　42　(5)　416-416　2000/08/30

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  188. 真菌マンナンはCD14/Toll-like receptor4を介してヒト単球を活性化する

    多田 浩之, 菅原 俊二, 島内 英俊, 高田 春比古

    歯科基礎医学会雑誌　42　(5)　416-416　2000/08/30

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  189. ヒト歯肉線維芽細胞のLPS応答のIFNγによる増強

    玉井 利代子, 作田 哲也, 松下 健二, 鳥居 光男, 菅原 俊二, 高田 春比古

    歯科基礎医学会雑誌　42　(5)　502-502　2000/08/30

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  190. ヒト歯肉線維芽細胞膜上のCD26/dipeptidyl peptidase IV ―サイトカインおよび菌体成分による発現増強― (日本炎症学会雑誌)

    根本英二, 菅原俊二, 高田春比古, 庄司 茂, 堀内 博

    日本炎症学会雑誌　20　(5)　597-602　2000/05

    Publisher: The Japanese Society of Inflammation and Regeneration

    DOI： 10.2492/jsir1981.20.597 　

    ISSN： 0389-4290

    More details Close

    CD 26/dipeptidyl peptidase IV (DPPIV) is a cell surface ectoenzyme which participates in immune and inflammatory reactions. We found that CD 26 was only partially expressed on human fibroblasts from periodontal tissues, whereas fibroblasts from lung and skin expressed CD 26 constitutively as revealed by flow cytometry. We examined the possible upregulation of CD 26-expression on human gingival fibroblasts in response to various stimulants. Interleukin (IL) -1 α, tumor necrosis factor (TNF) -α, interferon (IFN) -γ, lipopolysaccharide (LPS) from Porphyromonas gingivalis, Prevotella intermedia, and Escherichia coli and Prevotella glycoprotein augmented CD 26 expression on gingival fibroblasts. Among the stimulants, IL-1 α exhibited the most potent activity. Enzymatic activity of CD 26 was also induced by stimulation on fibroblasts. The upregulation of CD 26 mRNA expression upon stimulation with IL-1 α was also revealed by a quantitative RT-PCR assay. In the kinetic experiment, 48 h and several days were required for maximum CD 26 mRNA accumulation and CD 26 molecule expression on the cell surface, respectively. The addition of cycloheximide almost completely inhibited the accumulation of CD 26 mRNA induced by IL-1 α. These results suggested that induction of CD 26 on human gingival fibroblasts is regulated at the transcriptional level, and is also dependent on a de nove synthesized protein factor (s) .

  191. 歯肉線維芽細胞ならびに歯根膜線維芽細胞のCD14/Toll-like receptor(TLR)系とLPS応答

    玉井利代子, 畠山純子, 作田哲也, 松下健二, 鳥居光男, 菅原俊二, 高田春比古

    日本細菌学雑誌　55　(2)　2000

    ISSN： 0021-4930

  192. ムラミルジペプチド(MDP)とLPSないしリポタイコ酸(LTA)の相乗作用

    楊淑ファ, 玉井利代子, 菅原俊二, 高田春比古

    日本細菌学雑誌　55　(2)　2000

    ISSN： 0021-4930

  193. ヒト歯肉上皮細胞の各種菌体成分に対する不応答性

    上原亜希子, 玉井利代子, 菅原俊二, 高田春比古

    日本細菌学雑誌　55　(2)　2000

    ISSN： 0021-4930

  194. 細菌細胞壁ペプチドグリカンのヒト口腔線維芽細胞ならびに単球系細胞活性化作用

    畠山 純子, 菅原 俊二, 楊淑華, 杉山 明子, 奥田 禮一, 高田 春比古

    歯科基礎医学会雑誌　41　(5)　483-483　1999/08/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  195. 黒色色素産生菌LPSのヒト末梢血単核細胞に対する新奇な作用

    高橋 昌宏, 菅原 俊二, 力石 秀実, 高田 春比古

    歯科基礎医学会雑誌　41　(5)　481-481　1999/08/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  196. Prevotella intermedia ATCC 25611非内毒素性糖タンパクのCD14依存性および非依存性ヒト細胞活性化機構

    菅原 俊二, 畠山 純子, 高橋 昌宏, 力石 秀実, 高田 春比古

    歯科基礎医学会雑誌　41　(5)　401-401　1999/08/20

    Publisher: 歯科基礎医学会

    ISSN： 0385-0137

  197. Heterogeneous Expression and Release of CD14 by Human Gingival Fibroblasts and the Possible Role of CD14

    Sugawara Shunji

    Japanese journal of oral biology　41　(2)　98-107　1999/04/20

    Publisher: Japanese Association for Oral Biology

    ISSN： 0385-0137

  198. Lipoteichoic acid acts as an antagonist and an agonist of lipopolysaccharide on human gingival fibroblasts and monocytes in a CD14-dependent manner.

    Sugawara S, Arakaki R, Rikiishi H, Takada H

    Infect Immun　67　(4)　1623-1632　1999

  199. 菌体表層成分の認識機構と歯周疾患 (東北大学歯学雑誌)

    菅原俊二, 高田春比古

    東北大学歯学雑誌　18　(2)　187-187　1999

  200. 菌体表層成分と歯周病 試論 歯周組織におけるCD14分子の役割 (歯科基礎医学会雑誌)

    菅原俊二, 高田春比古

    歯科基礎医学会雑誌　40　(1)　1-16　1998

    Publisher: Japanese Association for Oral Biology

    DOI： 10.2330/joralbiosci1965.40.1 　

    ISSN： 0385-0137

  201. 抗溶連菌由来スーパー抗原により活性化されるT細胞の新しい生物学的意義． Invited

    岡本成史, 恩田時男, 菅原俊二, 根本英二, 力石秀実, 田村啓二, 熊谷勝男

    抗ウイルス化学療法の進歩（抗ウイルス化学療法研究会プロシーディング）　81-88　1994/07

  202. Induction of Acute Arthritis in Mice by Peptidoglycan Derived from Gram-Positive Bacteria and Its Possible Role in Cytokine Production

    Onta Tokio, Sashida Masami, Fujii Noriyuki, Sugawara Shunji, Rikiishi Hidemi, Kumagai Katsuo

    Japanese Journal of Microbiology　37　(7)　573-582　1993

    Publisher: Center For Academic Publications Japan

    ISSN： 0385-5600

    More details Close

    The activities of a water-soluble peptidoglycan fragment derived from Staphylococcus epidermidis (SEPS) were examined as to their role in proliferation of spleen mononuclear cells (SMNC) from various strains of mice, the production of cytokines in vitro, and the induction of an inflammatory reaction in vivo. The proliferation of SMNC from C3H/HeN, C57BL/6, AKR, DBA/2, and ddY mice in reaction to SEPS in vitro showed a peak on day 3 and was greater than that of SMNC from BALB/c mice. The cells of SMNC from C3H/HeN mice responsive to SEPS were indicated to be mainly macrophages. A time kinetics experiment showed a coincidence in the proliferation of SMNC in reaction to SEPS and the detection of colony-stimulating factor (CSF) activity. Interleukin 2 (IL-2) activity was not detected during the incubation periods. When SEPS was administered to mice, much stronger mRNA transcripts of granulocyte-macrophage (GM)-CSF were detected in the lungs of C3H/HeN mice than in BALB/c mice. On the other hand, the amounts of IL-1 and PGE2 produced by SMNC of BALB/c mice stimulated by SEPS were greater than those produced in C3H/HeN mice. SEPS was confirmed to induce arthritis in BALB/c mice, but not in C3H/HeN mice. Our findings suggest that the production of GM-CSF is involved in the in vitro proliferation of SMNC in reaction to SEPS and that along with IL-1 and PGE2 production, contributes to the inflammation by SEPS in vivo.

  203. Proliferation of human peripheral blood lymphocytes induced by Gram-positive bactria : Its specific reaction accompanied by induction of immature T Iymphocytes

    Shunji Sugawara, Department of Oral Microbiology Tohoku University School of Dentistry

    7　(1)　13-27　1988/06/30

    ISSN： 0287-3915

Show all ︎Show first 5

Books and Other Publications 3

  1. 研究社歯学英和辞典

    渡辺, 誠

    研究社　2012/01

    ISBN: 9784767434704

  2. 分子細胞生物学辞典

    村松, 正實

    東京化学同人　2008/10

    ISBN: 9784807906871

  3. 第２版 口腔微生物学・免疫学

    浜田茂幸, d, 菅原俊二, 高田春比古

    医歯薬出版　2005/08

Presentations 95

  1. Fusobacterium nucleatum感染によるマスト細胞からの細胞外トラップ産生と炎症誘導

    多田浩之, 西岡貴志, 松下健二, 菅原俊二

    第61回歯科基礎医学会学術大会　2019/10

  2. Porphyromonas gingivalisジンジパインによりマスト細胞が産生するIL-31は、歯肉上皮細胞のclaudin-1発現を抑制しバリア破綻を誘導する

    多田浩之, 西岡貴志, 沼崎研人, 根本英二, 松下健二, 菅原俊二

    第73回日本細菌学会東北支部会　2019/08

  3. ゾレドロネート静脈内投与マウスでのLPSによるIL-1αおよびIL-1βの増加に関してのクロドロネートによる抑制

    鈴木 飛佳理, 坂東 加南, 木山 朋美, 大泉 丈史, 多田 浩之, 遠藤 康男, 菅原 俊二, 高橋 哲

    日本口腔科学会雑誌　2019/07

  4. 筋機能時における好中球由来IL1βの役割

    土谷 昌広, チャウィワンナコン・チャヤニ, 佐々木 啓一, 菅原 俊二, 渡邉 誠, 遠藤 康男

    Journal of Oral Biosciences Supplement　2018/09

  5. Zoledronate(bisphosphonate)静脈投与マウスでのLPSによるIL-1産生増強とclodronate(bisphosphonate)による抑制

    鈴木 飛佳理, 坂東 加南, 多田 浩之, 木山 朋美, 大泉 丈史, 船山 ひろみ, 菅原 俊二, 高橋 哲, 遠藤 康夫

    Journal of Oral Biosciences Supplement　2018/09

  6. P.gingivalis感染によりマスト細胞から産生されたIL‐31はclaudin‐1発現抑制を介して歯肉上皮バリア破綻を誘導する

    多田浩之, 沼崎研人, 西岡貴志, 松下健二, 菅原俊二

    Journal of Oral Biosciences Supplement (Web)　2018

  7. Neutrophil extracellular trapsによるヒト血管内皮細胞のDel-1産生抑制

    多田 浩之, 西岡貴志, 松下 健二, 菅原 俊二

    Journal of Oral Biosciences Supplement　2017/09

  8. 舌下免疫療法による食物アレルギー予防効果の解析

    秋山 なつみ, 桃北 萌子, 宍戸 香, 黒石 智誠, 菅原 俊二

    Journal of Oral Biosciences Supplement　2017/09

  9. 細胞外purine nucleotide刺激はヒト口腔上皮細胞における炎症性サイトカイン産生を増強する

    宍戸 香, 黒石 智誠, 菅原 俊二

    Journal of Oral Biosciences Supplement　2017/09

  10. CXCL4は新規Ni結合タンパク質でありNiアレルギーを増強する

    黒石 智誠, 田中 志典, 遠藤 康男, 菅原 俊二

    Journal of Oral Biosciences Supplement　2016/09

  11. ヒト唾液腺細胞はATP刺激によりIL-6を産生する

    根本 恭利, 黒石 智誠, 菅原 俊二

    Journal of Oral Biosciences Supplement　2015/09

  12. リン酸トランスポーターSLC20/34阻害薬はマウスBRONJ(bisphosphonate-related osteonecrosis of the jaw)を抑制する

    木山 朋美, 土谷 昌広, 佐々木 啓一, 菅原 俊二, 河井 俊久, 遠藤 康男

    Clinical Calcium　2015/04

  13. BRONJ(bisphosphonate-related osteonecrosis of the jaw)の治療 etidronate置換療法の試み

    大泉 丈史, 山口 晃史, 鈴木 飛佳理, 土谷 昌広, 菅原 俊二, 高橋 哲, 遠藤 康男

    Clinical Calcium　2015/04

  14. ビオチン欠乏に伴うアミノ酸代謝異常と抗酸化能の低下

    黒石 智誠, 菅原 俊二

    ビタミン　2015/04

  15. 窒素含有bisphosphonates(N-BPs)の炎症壊死作用のLPSによる増強

    鈴木 飛佳理, 島 和弘, 山口 晃史, 大泉 丈史, 菅原 俊二, 高橋 哲, 遠藤 康男

    Clinical Calcium　2015/04

  16. 窒素含有bisphosphonates(N-BPs)治療患者での顎骨壊死 N-BPsのetidronate(non-N-BP)への置換の試み

    大泉 丈史, 山口 晃史, 鈴木 飛佳理, 土谷 昌広, 菅原 俊二, 高橋 哲, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014/09

  17. 粉末食長期飼育はマウス糖代謝機構を障害し社会性行動の変化をもたらす

    千葉 航, 土谷 昌広, 渡邉 誠, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014/09

  18. Clodronateとetidronate(窒素非含有bisphosphonates)は脊髄神経小胞リン酸トランスポーターSLC17を抑制して鎮痛作用を発揮する

    島 和弘, 山本 照子, 菅原 俊二, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014/09

  19. 窒素含有bisphosphonates(N-BPs)の炎症壊死作用 LPSによる増強

    鈴木 飛佳理, 島 和弘, 佐藤 衣莉, 山口 晃史, 大泉 丈史, 菅原 俊二, 高橋 哲, 遠藤 康男

    Journal of Oral Biosciences Supplement　2014/09

  20. 咀嚼様運動負荷によるマウス咬筋でのIL-6発現に関する研究

    木山朋美, 土谷昌広, 西岡貴志, 菅原俊二, 遠藤康男, 渡辺誠

    第52回東北大学歯学会　2007/12/12

  21. 骨吸収抑制薬bisphosphonates (BPs) による顎骨壊死：基礎研究に基づく発症機序および予防・治療に関する考察

    大泉丈史, 山口晃史, 菅原俊二, 遠藤康男

    第52回東北大学歯学会　2007/12/12

  22. マウスにおけるニッケルアレルギー：交差反応およびLPSのニッケル濃度におよぼす効果

    金原正敬, 黒石智誠, 菅原俊二, 遠藤康男

    第37回日本免疫学会総会・学術集会　2007/11/20

  23. マウスにおけるニッケルアレルギー：感作過程における各種微生物成分と炎症性物質の効果

    高橋春江, 金原正敬, 黒石智誠, 高田春比古, 菅原俊二, 遠藤康男

    第37回日本免疫学会総会・学術集会　2007/11/20

  24. Modulation of metal allergy by biotin via regulation of IL-1β production

    黒石智誠, 金原正敬, 遠藤康男, 菅原俊二

    第37回日本免疫学会総会・学術集会　2007/11/20

  25. Muramyl-dipeptideによるマウス組織におけるIL-1βの産生：エンドトキシンショック増強効果との関連性

    四釜洋介, トウ雪, 島内英俊, 高田春比古, 菅原俊二, 遠藤康男

    第37回日本免疫学会総会・学術集会　2007/11/20

  26. 骨吸収抑制薬bisphosphonates (BP) の壊死作用：窒素含有BP (NBP) と窒素非含有PB (non-NBP) の作用の違い

    大泉丈史, 山口晃史, 船山ひろみ, 黒石智誠, 菅原俊二, 遠藤康男

    第37回日本免疫学会総会・学術集会　2007/11/20

  27. Concanavalin A肝炎のLPS前投与による抑制：血小板とマクロファージの関与

    兪志前, 山口晃史, DENG Xue, 黒石智誠, 一石英一郎, 菅原俊二, 遠藤康男

    第37回日本免疫学会総会・学術集会　2007/11/20

  28. ヒスタミン刺激によるヒト単球様細胞表面NKG2Dリガンド発現の抑制

    佐藤隆太郎, 黒石智誠, 遠藤康男, 菅原俊二

    第37回日本免疫学会総会・学術集会　2007/11/20

  29. K5/IL-18 Tg マウスにおける唾液腺浸潤細胞の解析

    佐藤恭子, 黒石智誠, 西岡貴志, 菅原由美子, 星野友昭, 菅原俊二

    第37回日本免疫学会総会・学術集会　2007/11/20

  30. シェーグレン症候群病態発現におけるIL-18とIL-17の関与

    酒井 梓, 菅原由美子, 黒石智誠, 笹野高嗣, 菅原俊二

    第35回日本臨床免疫学会総会　2007/10/19

  31. IL-18はIL-17と共同してシェーグレン症候群患者唾液腺における病態発現に寄与する

    酒井 梓, 菅原由美子, 黒石智誠, 笹野高嗣, 菅原俊二

    第16回日本シェーグレン症候群研究会　2007/09/21

  32. 窒素含有bisphosphonates (NBPs) の壊死作用：clodronate (Clo, non-NBP) による抑制とLPSによる増強

    大泉丈史, 中目晴子, 山口晃史, 川村仁, 黒石智誠, 菅原俊二, 遠藤康男

    第49回歯科基礎医学会学術大会　2007/08/30

  33. IL-18 Tg マウスにおける唾液腺浸潤リンパ球の解析

    佐藤恭子, 黒石智誠, 西岡貴志, 菅原由美子, 菅原俊二

    第49回歯科基礎医学会学術大会　2007/08/30

  34. ビオチンによる金属アレルギー炎症の制御

    黒石智誠, 金原正敬, 遠藤康男, 菅原俊二

    第49回歯科基礎医学会学術大会　2007/08/30

  35. マウスにおける金属アレルギー：交差反応およびLPSのニッケル濃度におよぼす効果

    金原正敬, 黒石智誠, 菅原俊二, 遠藤康男

    第49回歯科基礎医学会学術大会　2007/08/30

  36. マウスにおけるニッケルアレルギー：感作過程における微生物環境と炎症の効果

    高橋春江, 金原正敬, 黒石智誠, 高田春比古, 菅原俊二, 遠藤康男

    第49回歯科基礎医学会学術大会　2007/08/30

  37. ヒスタミンによるヒト単球様細胞におけるNKG2Dリガンド発現の抑制

    佐藤隆太郎, 黒石智誠, 越後成志, 遠藤康男, 菅原俊二

    第49回歯科基礎医学会学術大会　2007/08/30

  38. Muramyl-dipeptideによるマウス組織におけるIL-1βの産生：エンドトキシンショック（EtxS）増強効果との関連性

    四釜洋介, 雪, 島内英俊, 高田春比古, 菅原俊二, 遠藤康男

    第49回歯科基礎医学会学術大会　2007/08/30

  39. 窒素含有bisphosphonates (NBPs) の壊死作用：etidronateのNBPs代用薬としての可能性

    中目晴子, 大泉丈史, 船山ひろみ, 山口晃史, 川村仁, 黒石智誠, 菅原俊二, 遠藤康男

    第49回歯科基礎医学会学術大会　2007/08/30

  40. Keratin 5 (k5)/IL-18トランスジェニックマウスでの唾液腺障害の誘導

    西岡貴志, 黒石智誠, 菅原由美子, 笹野高嗣, 遠藤康男, 菅原俊二

    第49回歯科基礎医学会学術大会　2007/08/30

  41. 窒素含有bisphosphonates (NBPs) の壊死作用：clodronate (Clo, non-NBP) による抑制とLPSによる増強

    大泉丈史, 山口晃史, 川村仁, 菅原俊二, 遠藤康男

    第51回東北大学歯学会　2007/06/22

  42. Biotin modulates metal allergy via regulation of IL-1 beta production International-presentation

    Kuroishi T, Sato N, Endo Y, Sugawara S

    8th World Congress on Inflammation　2007/06/16

  43. 炎症性サイトカイン及びLPS刺激によるヒト歯肉線維芽細胞からのIL-8産生誘導におけるヒスタミンの相乗効果とその機序

    南 匠, 黒石智誠, 小澤亜紀子, 遠藤康男, 島内英俊, 菅原俊二

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  44. マウスにおけるニッケルアレルギー：交差反応およびLPSのニッケル濃度におよぼす効果

    金原正敬, 佐藤直毅, 黒石智誠, 菅原俊二, 遠藤康男

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  45. マウスにおけるニッケルアレルギー：感作過程における各種微生物成分および炎症性物質の効果

    高橋春江, 佐藤直毅, 金原正敬, 黒石智誠, 高田春比古, 菅原俊二, 遠藤康男

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  46. ヒスタミンによるヒト単球様細胞におけるNKG2Dリガンド発現抑制

    佐藤隆太郎, 黒石智誠, 越後成志, 遠藤康男, 菅原俊二

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  47. ビオチン欠乏に伴うTNF-α産生増強

    黒石智誠, 遠藤康男, 菅原俊二

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  48. IL-18 Tg マウスにおける唾液腺浸潤リンパ球の解析

    佐藤恭子, 黒石智誠, 西岡貴志, 菅原由美子, 笹野高嗣, 菅原俊二

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  49. Muramyl-dipeptideによるマウス組織におけるIL-1bの産生：LPS作用の増強効果との関連性

    四釜洋介, 雪, 島内英俊, 高田春比古, 菅原俊二, 遠藤康男

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  50. 窒素含有bisphosphonates (NBPs) の壊死作用：clodronate (Clo, non-NBP) による抑制とLPSによる増強

    大泉丈史, 中目晴子, 山口晃史, 川村仁, 黒石智誠, 菅原俊二, 遠藤康男

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  51. 窒素含有bisphosphonates (NBPs) の壊死作用：etidronateのNBPs代用薬としての可能性

    中目晴子, 大泉丈史, 船山ひろみ, 山口晃史, 川村仁, 黒石智誠, 菅原俊二, 遠藤康男

    第4回東北大学バイオサイエンスシンポジウム　2007/06/04

  52. IL-18 expressed in salivary gland cells induces IL-6 and IL-8 in the cells in synergy with IL-17 International-presentation

    Sakai A, Kuroishi T, Sugawara Y, Sasano T, Sugawara S

    International Symposium for Interface Oral Health Science　2007/02/18

  53. Histamine amplifies proinflammatory signaling cascade in human gingival fibroblasts International-presentation

    Minami T, Kuroishi T, Ozawa A, Endo Y, Shimauchi H, Sugawara S

    International Symposium for Interface Oral Health Science　2007/02/18

  54. Priming effects of microbial or inflammatory agents on metal allergies International-presentation

    Sato N, Kinbara M, Kuroishi T, Takada H, Kimura K, Sugawara S, Endo Y

    International Symposium for Interface Oral Health Science　2007/02/18

  55. Phagocytic macrophages do not contribute to the induction of serum IL-18 in mice treated with Propionibacterium acnes and lipopolysaccharide International-presentation

    Nishioka T, Kuroishi T, Yu Z, Sugawara Y, Sasano T, Endo Y, Sugawara S

    International Symposium for Interface Oral Health Science　2007/02/18

  56. Infiltration of immune cells in salivary gland by IL-18 overexpression in mice International-presentation

    Sato K, Kuroishi T, Nishioka T, Sugawara Y, Hoshino T, Sasano T, Sugawara S

    International Symposium for Interface Oral Health Science　2007/02/18

  57. Biotin deficiency up-regulates TNF-α production in vivo and in vitro International-presentation

    Kuroishi T, Endo Y, Sugawara S

    International Symposium for Interface Oral Health Science　2007/02/18

  58. LPSによるマウス肝臓への急性血小板肝臓集積とアナフィラキシー様ショック反応：Kupffer細胞の関与

    山口晃史, 横地高志, 菅原俊二, 高田春比古, 遠藤康男

    日本免疫学会　2006/12/11

  59. LPSによるマウス肺への急性血小板集積とアナフィラキシー様ショック反応 アドレナリンα受容体の関与

    四釜洋介, 船山ひろみ, 島内英俊, 横地高志, 菅原俊二, 高田春比古, 遠藤康男

    日本免疫学会　2006/12/11

  60. 窒素含有bisphosphonates（N-BPs）による顎骨壊死のマウスモデル：LPSによる増強およびnon-N-BPのclodronateによる抑制

    大泉丈史, 山口晃史, 船山ひろみ, 菅原俊二, 遠藤康男

    日本免疫学会　2006/12/11

  61. Concanavalin A (Con A) によるマウス肝炎：マクロファージ（Mφ）と血小板（PLT）の役割

    船山ひろみ, 小野栄夫, 菅原俊二, 高田春比古, 遠藤康男

    日本免疫学会　2006/12/11

  62. Induction of serum IL-18 from keratinocytes/epithelial cells in mice treated with Propionibacterium acnes and LPS

    Nishioka T, Kuroishi T, Yu Z, Sugawara Y, Endo Y, Sugawara S

    日本免疫学会　2006/12/11

  63. OVA抗原静脈注射によるhistidine decarboxylaseの誘導とhistamineレベル変化：肥満細胞、非肥満細胞およびIL-1の関与

    トウ 雪, 岩倉洋一郎, 菅原俊二, 遠藤康男

    日本免疫学会　2006/12/11

  64. Characterization and function of IL-18 expressed in salivary gland cells in culture

    Sakai A, Kuroishi T, Sugawara Y, Sugawara S

    日本免疫学会　2006/12/11

  65. Histamine synergistically augments proinflammatory cytokine-induced signaling cascade in human gingival fibroblasts

    Minami T, Kuroishi T, Shimauchi H, Endo Y, Sugawara S

    日本免疫学会　2006/12/11

  66. 自然免疫によるNiアレルギーの誘導

    佐藤直毅, 金原正敬, 黒石智誠, 岩倉洋一郎, 菅原俊二, 遠藤康男

    日本免疫学会　2006/12/11

  67. Biotin deficiency augments TNF-α production in vivo and in vitro

    Kuroishi T, Endo Y, Sugawara S

    日本免疫学会　2006/12/11

  68. マウスにおける金属アレルギー：LPSによる増強と交差反応

    金原正敬, 佐藤直毅, 黒石智誠, 菅原俊二, 遠藤康男

    日本免疫学会　2006/12/11

  69. Histamine amplifies immune response of human gingival fibroblasts International-presentation

    Minami T, Kuroishi T, Ozawa A, Shimauchi H, Endo Y, Sugawara S

    International Endotoxin and Innate Immunity Society　2006/11/09

  70. Human parotid saliva contains soluble Toll-like receptor (TLR) 2 and modulates TLR2-mediated interleukin-8 production by monocytic cells International-presentation

    Kuroishi T, Sakai A, Sugawara Y, Tanaka Y, Komine K, Sugawara S

    International Endotoxin and Innate Immunity Society　2006/11/09

  71. Lipopolysaccharide promotes and augments metal allergies in mice, dependent on innate immunity and histidine decarboxylase International-presentation

    Sato N, Kinbara M, Kuroishi T, Kimura K, Iwakura Y, Ohtsu H, Sugawara S, Endo Y

    International Endotoxin and Innate Immunity Society　2006/11/09

  72. 窒素をもつ骨吸収抑制剤bisphosphonates (N-BPs) の炎症作用：コレステロール合成経路、マクロファージ、Ｔ細胞の関与

    トウ 雪, 笹野高嗣, 菅原俊二, 遠藤康男

    歯科基礎医学会　2006/09/21

  73. 窒素をもつ骨吸収抑制剤bisphosphonates (N-BPs) の炎症・壊死作用：non-N-BP clodronate (Clo) による抑制とLPSによる増強

    大泉丈史, 船山ひろみ, 山口晃史, 川村仁, 菅原俊二, 遠藤康男

    歯科基礎医学会　2006/09/21

  74. Ni (＋LPS) 感作マウスでのNiと他金属との交差allergy反応

    金原正敬, 佐藤直毅, 黒石智誠, 菅原俊二, 遠藤康男

    歯科基礎医学会　2006/09/21

  75. Adrenaline (Ad) に対するin vivoでの血小板反応：adrenergic antagonists、マクロファージ（Mφ）の枯渇、および捕体C5阻害薬の効果

    四釜洋介, 島内英俊, 菅原俊二, 遠藤康男

    歯科基礎医学会　2006/09/21

  76. LPSは自然免疫およびヒスタミン合成酵素histidine decarboxylaseを介して金属（M）アレルギー（A）を促進する

    佐藤直毅, 金原正敬, 黒石智誠, 木村幸平, 菅原俊二, 遠藤康男

    歯科基礎医学会　2006/09/21

  77. ビオチン欠乏はマクロファージによるTNF-α産生を増強する

    黒石智誠, 栢島亜由美, 遠藤康男, 菅原俊二

    歯科基礎医学会　2006/09/21

  78. Propionibacterium acnes/LPS処理したマウスのケラチノサイト/上皮細胞からの血清IL-18産生誘導

    西岡貴志, 兪志前, 菅原由美子, 笹野高嗣, 遠藤康男, 菅原俊二

    歯科基礎医学会　2006/09/21

  79. 細胞外カルシウムのマクロファージ様細胞が持つ潜在的骨形成能促進効果

    本田義知, 穴田貴久, 鎌倉慎治, 中村雅典, 菅原俊二, 鈴木治

    歯科基礎医学会　2006/09/21

  80. 唾液腺の病態発現におけるIL-18の役割

    酒井梓, 黒石智誠, 菅原由美子, 笹野高嗣, 菅原俊二

    歯科基礎医学会　2006/09/21

  81. ヒト歯肉線維芽細胞おけるヒスタミンの免疫反応の増強

    南 匠, 黒石智誠, 小澤亜紀子, 遠藤康男, 島内英俊, 菅原俊二

    歯科基礎医学会　2006/09/21

  82. サイトメガロウイルス感染における臓器のHDC活性の動態

    今井信一, 鈴木宏治, 門馬祐子, 遠藤康男, 菅原俊二, 真柳秀昭

    歯科基礎医学会　2006/09/21

  83. ヒト耳下腺唾液に発現するIL-18の役割

    酒井梓, 黒石智誠, 菅原由美子, 笹野高嗣, 菅原俊二

    日本口腔粘膜学会　2006/06/30

  84. Induction of serum IL-18 from keratinocytes/epithelial cells through neutrophil serine protease-mediated protease-activated receptor 2 (PAR2) activation International-presentation

    Nishioka T, Ikawa K, Yu Z, Sugawara Y, Sasano T, Endo Y, Sugawara S

    International Association of Dental Research　2006/06/28

  85. 窒素含有bisphosphonates (N-BP) の炎症作用のclodronate（C, non-N-BP）による抑制とLPSによる増強：機序解明へのBP-line応用の試み

    大泉丈史, 船山ひろみ, 山口晃史, 川村仁, 菅原俊二, 遠藤康男

    東北大学歯学会　2006/06/14

  86. Ni (＋LPS) 感作マウスでのNiと他金属との交差allergy反応

    金原正敬, 佐藤直毅, 木村幸平, 菅原俊二, 遠藤康男

    東北大学歯学会　2006/06/14

  87. ヒト耳下腺唾液による単球様細胞株のTLR2刺激応答性の制御

    黒石智誠, 酒井梓, 小峯健一, 菅原俊二

    東北大学バイオサイエンスシンポジウム　2006/05/29

  88. Propionibacterium acnes/LPS処理したマウスのケラチノサイト/上皮細胞からの血清IL-18産生誘導

    西岡貴志, 兪志前, 菅原由美子, 笹野高嗣, 遠藤康男, 菅原俊二

    東北大学バイオサイエンスシンポジウム　2006/05/29

  89. 窒素を分子内に持つbisphosphonates (N-BPs) の炎症作用：コレステロール合成経路、マクロファージ、Ｔ細胞の関与

    トウ 雪, 兪志前, 菅原俊二, 遠藤康男

    東北大学バイオサイエンスシンポジウム　2006/05/29

  90. ヒト唾液腺の免疫機構に対するIL-18の関与

    酒井梓, 黒石智誠, 菅原由美子, 笹野高嗣, 菅原俊二

    東北大学バイオサイエンスシンポジウム　2006/05/29

  91. ヒト歯肉線維芽細胞からのIL-8産生誘導におけるヒスタミンと炎症性サイトカイン及びLPSのMAPKとNF-kB経路を介する相乗効果

    南 匠, 小澤亜紀子, 黒石智誠, 遠藤康男, 島内英俊, 菅原俊二

    東北大学バイオサイエンスシンポジウム　2006/05/29

  92. LPSは自然免疫およびヒスタミン合成酵素histidine decarboxylaseを介して金属アレルギーを促進する

    佐藤直毅, 金原正敬, 黒石智誠, 木村幸平, 岩倉洋一郎, 大津浩, 菅原俊二, 遠藤康男

    東北大学バイオサイエンスシンポジウム　2006/05/29

  93. ヒト歯肉線維芽細胞からのIL-8産生誘導におけるヒスタミンと炎症性サイトカインの相乗効果

    南 匠, 小澤亜紀子, 菅原俊二, 島内英俊

    日本歯周病学会　2006/04/27

  94. 歯周疾患における唾液中催炎性ラクトフェリンポリペプチドの性状およびその産生機構について

    小澤亜紀子, 小峯健一, 黒石智誠, 南 匠, 菅原俊二, 島内英俊

    日本歯周病学会　2006/04/27

  95. アルギニン特異的ジンジパインによるPARを介するヒト歯肉線維芽細胞の肝細胞増殖因子産生増強

    上原亜希子, 今村隆寿, 菅原俊二, 高田春比古

    日本細菌学会　2006/03/29

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Industrial Property Rights 2

  1. ラクトフェリン・ポリペプチド及びその製造法

    菅原 俊二, 小峯 健一

    Property Type: Patent

  2. ラクトフェリン・ポリペプチドの測定による歯周病リスクの検査方法

    菅原 俊二, 小峯 健一

    特許第4029988号

    Property Type: Patent

Research Projects 38

  1. 新規ニッケル結合性T細胞を基軸としたニッケルアレルギー病態形成機構の解明

    黒石 智誠, 菅原 俊二, 江草 宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  2. Elucidation of the therapeutic effect of nickel allergy by sublingual immunotherapy

    Kuroishi Toshinobu

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2019/04/01 - 2022/03/31

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    Metal allergies are classified as type-IV allergies and induced by metal ions eluted from various metal products. Nickel (Ni) is the most frequent metal allergen. Sublingual immunotherapy (SLIT) is an allergen-specific immunotherapy and used for the treatment of type-I allergies, such as allergic rhinitis. SLIT induces allergen-specific immunotolerance by allergens administration through sublingual mucosa. In this study, we investigated the treatment effects of SLIT on Ni allergy mouse model. SLIT with Ni and a Ni-binding protein CXCL4 efficiently induced immunotolerance to Ni. Moreover, vitamin D3 derivative augmented the treatment effects of SLIT on Ni allergy. These results suggest that SLIT using metal-binding protein and vitamin D3 derivative is an effective treatment for metal allergies.

  3. Study on oral mucosal immune regulation on the axis of activated vitamin D3

    Sugawara Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2019/04/01 - 2022/03/31

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    This study was aimed to elucidate effects of activated vitamin D3 (VD3) on oral mucosal immune system. We first address the outcome of VD3 supplementation of sublingual immunotherapy (SLIT) in a murine delayed-type hypersensitivity (DTH) model. SLIT with VD3 significantly inhibited DTH response after the second challenge. Adoptive transfer of regulatory T (Treg) cells from mice treated with SLIT with VD3 exhibited therapeutic effects on OVA-DTH. Transcriptome analysis of Treg cells revealed that SLIT with VD3 generated functionally different Treg cells with altered gene expression profile. In the vitamin D3 deficient mice, expression of genes which are essential for IgA class switch from IgM, was markedly down-regulated. Taken together, these results suggest that VD3 play as important role for control of oral mucosal immune responses.

  4. Analysis of the pathogenic roles and control mechanisms of inflammasome in sialadenitis

    MUROI AZUSA

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2017/04/01 - 2020/03/31

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    Proinflammatory cytokine interleukin (IL)-18 involves in pathology of Sjogren’s syndrome. Caspase-1 is a proteolytic enzyme which cleaves pro-IL-18 to bioactive mature IL-18, and activated by inflammasome, a large protein complex including caspase-1. Purine nucleotides are endogenous danger signal and activate inflammasome. In this study, We analyzed the expression of IL-18 and inflammasome components in salivary glands, inflammatory roles of purine nucleotides in oral epithelial cells. Salivary gland macrophages constitutively expressed mRNA of IL-18, caspase-1 and inflammasome components, suggesting that IL-18 from salivary gland macrophages involve in sialadenitis. Purine nucleotides induced the significantly grater production of IL-6 by oral epithelial cells. Moreover, proinflammatory cytokine IL-1 significantly augmented the production of IL-6 induced by purine nucleotides. These results suggest that purine nucleotides play the pathological roles in inflammation of oral mucosa.

  5. Analysis of the mechanisms by which Ni-binding dendritic cells induce Ni allergy

    Kuroishi Toshinobu, TANAKA Yukinori

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2016/04/01 - 2019/03/31

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    Metal allergies have been classified as Th1-dependent type-IV allergies. The most frequent metal allergen is nickel (Ni). In this study, we analyzed the Ni-binding ability of DCs using the fluorescent metal indicator. Classical DCs (cDCs) and plasmacytoid DCs were detected in the draining LNs. cDCs were further classified into MHC class II hi CD11c int migratory cDCs and MHC class II int CD11c hi resident cDCs. The Ni-binding ability of the migratory cDCs was significantly higher in skin-draining and submandibular LNs than mesenteric LNs. On the other hand, the Ni-binding ability of the resident cDCs was significantly lower than that of the migratory cDCs, but no significant differences were detected between LNs. Moreover, subcutaneous injection of Ni-treated DCs purified from the skin-draining LNs induced Ni-allergic inflammation in Ni-sensitized mice. These results demonstrate that migratory cDCs in the skin-draining LNs have Ni-binding capability and elicit Ni allergy.

  6. Study on causes of reduced umami sensitivity

    Sasano Takashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2016/04/01 - 2018/03/31

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    Quantitative measurement of glutamate in saliva using high performance liquid chromatography (HPLC) and quantitative analysis of umami receptor genes expression by real-time PCR method were performed to determine the cause of reduced umami sensitivity. As a result, the amount of glutamate in saliva in patients with reduced umami sensitivity had a tendency to be lower than that in subjects with normal umami sensitivity. On the other hand, there was no significant difference in the expression levels of the umami receptor genes expression between patients with reduced umami sensitivity and healthy subjects. These results suggested that reduced umami sensitivity could be related to the amount of glutamate in saliva.

  7. Basic research for development of effective inducing strategy of sublingual immune tolerance

    SUGAWARA Shunji, TANAKA Yukinori, LU Lu, SHISHIDO Kaori

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2016/04/01 - 2018/03/31

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    Sublingual immunotherapy (SLIT) is an allergen-specific treatment for allergy. SLIT increases allergen tolerance with safety and effective effect. However, the effect is not always strong enough, strategy to increase SLIT is anticipated. This study aimed at finding a substance that augment the effect of SLIT by using delayed-type hypersensitivity mouse mode. Among candidate substances that can induce regulatory T cells, we succeeded to find out one substance (referred to substance A). SLIT enhancing effect by substance A was long-lasting, but production fo retinoic acid by sublingual mucosal dendritic cells. We are still challenging to elucidate the underlying mechanism.

  8. Mechanism of sublingual immune tolerance induction by cross-talking with gut mucosal immunity

    SUGAWARA Shunji, ISHII Naoto, TANAKA Yukinori, NAGASHIMA Hiroyuki, LU Lu, SHISHIDO Kaori

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2015/04/01 - 2018/03/31

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    Sublingual immunotherapy (SLIT) is an allergen-specific treatment for allergy. SLIT operates by acting on the sublingual mucosa and increases allergen tolerance with safety and effective effect. However, the underlying immunological mechanism remain unclear. This study aimed at providing evidence that sublingual immune tolerance is induced by cross-talking with gut mucosal immunity. This study showed that after sublingual application of antigen, antigen was captured by macrophages, transferred to migratory dendritic cells, and antigen-specific regulatory T cells were induced in the draining (submandibular) lymph modes. This study also showed that Langerhans cells in sublingual mucosa were not responsible for the induction of sublingual immune tolerance, and that sublingual immune tolerance was related to intestinal immune tolerance.

  9. Therapeutic innovation in oral mucosal leasions with erosion and ulcer by analyzing antigen presenting ability and autophagy

    Sugawara Yumiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2014/04/01 - 2018/03/31

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    Retrospective study was performed at 12 facilities on efficacy and safety of Cepharanthin (CEP) long-term use for the patient with oral lichen planus (OLP). The degree of the severity classified to, before and after 4weeks and 6 months and at the end point of the CEP use was assessed. The mean dosage period of the CEP use was 415 days, and the daily average dosage was 11.6mg. The high improvement rate was accepted in almost all clinical types and the location of the lesions by CEP use. Long-term use showed the higher efficacy for improving OLP. On the other hand, the dosage of CEP showed no significant difference for the improvement of OLP. High improvement rate was recognized even in the case without steroid use. Finally, eighty percent of the OLP cases showed significant efficacy, in addition, there was no significant adverse events due to the side effects. Thus, CEP use is considered to have significant efficacy for the treatment of OLP without side effects.

  10. Expression of umami-taste-related genes in the tongue.

    Sasano Takashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2014/04/01 - 2017/03/31

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    Expression of taste-related genes in the tongue was analysed to develop a technique for genetic diagnosis of umami taste disorders.Gustducin-positive cells were observed in the samples, indicating the presence of taste cells. Gene expression of b-actin, GNAT3, T1R1 and T1R3 was detected in all seven samples tested, while that of mGluR1 was detected in four samples. Sequence analysis by NCBI Blast showed that each polymerase chain reaction product had a 99% rate of identification of its target sequence. Stimulation of the tongue with monosodium glutamate significantly upregulated the gene expression levels of T1R1 and T1R3, indicating that this method can detect alterations in umami-related gene expression. Thus, evaluation of the expression of the umami receptor genes, T1R1 and T1R3, in the tongue may be clinically useful for objective genetic diagnosis of umami taste disorders.

  11. Analysis of the human salivary-gland apoptotic pass way for Sjogren's syndrome.

    MUROI AZUSA

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2013/04/01 - 2017/03/31

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    Sjogren’s syndrome is an inflammatory autoimmune disease, predominantly characterized by lymphocytic infiltration of the exocrine glands. In this study, to establish prophylactic and therapeutic strategies for this disorder, we examined the association between interleukin 18 (IL-18) and the apoptosis pathway in the salivary gland tissues of humans. The HSG cell line expresses caspase-1, which processes the IL-18 precursor protein into its mature form. However, ASC and NLRP3, which together with caspase-1 constitute the imflammasome complex, were not detected in these cells. Furthermore, we detected no change in the activity of intracellular caspase-1, even when the cells were stimulated with ATP and nigericin to induce intracellular K+, a factor known to trigger the imflammasome. Therefore, we infer that the activation of IL-18 in this cell line occurs without the activation of the imflammasome.

  12. Thrapeutic effects of biotin on allergic dermatitis through Th balance modulation

    Kuroishi Toshinobu, SUGAWARA SHUNJI, TANAKA YUKINORI

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2013/04/01 - 2016/03/31

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    Biotin is a water-soluble B complex vitamin and functions as a co-factor of five indispensable carboxylases in cells. It was reported that serum biotin concentrations are significantly lower in atopic dermatitis patients. In this study, we investigated the effects of biotin intake on atopic dermatitis by using mouse model. However, no significant differences were detected in symptoms of atopic dermatitis between biotin-deficient and biotin-sufficient mice. On the other hand, concentrations of several amino acids, such as methionine and cysteine were significantly lower in liver taken from biotin-deficient mice than biotin-sufficient mice. Moreover, anti-oxidant capacities were significantly lower in biotin-deficient cells than biotin-sufficient cells.

  13. Relationship among metal, resin, infection, and allergy

    ENDO Yasuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2012/04/01 - 2015/03/31

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    Concerning the relationship between resin monomers (RMs) and allergies, we found the followings. (i) 2－Hydroxyethyl metacrylate (HEMA) and methyl methacrylate (MMA), both typical RMs, act as adjuvants that promote nickel (Ni)-allergy at the steps of both the sensitization and elicitation. (ii) RMs also promoted the allergies induced by hydroquinone (widely used as an inhibitor of RM-polymerization) and oxazolone (a hapten widely used in experiments). These findings strongly suggest that what were previously thought of as “RM-allergies” might include allergies caused by antigens other than RMs. From now, RMs should be recognized not only as antigens but also as adjuvants that promote allergies induced by other antigens.

  14. Identification and function of Ni-binding carrier protein that induce Ni allergy

    SUGAWARA Shunji, KUROISHI Toshinobu, ENDO Yasuo, MURAMOTO Koji, KINBARA Masayuki, BANDO Kanan

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2012/04/01 - 2015/03/31

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    Metal ions are allergens that cause allergic contact dermatitis, and nickel (Ni) has been shown to be the most frequent metal allergens. Metal ions become antigens by binding with self-carrier proteins, but their identity is still unclear. In this study, we identified an Ni-binding carrier protein that cause Ni allergy form LPS-sensitized murine serum. This protein directly bound to Ni ion and reduced the threshold of Ni concentration that require to induce Ni allergy, whereas it did not alter the quality of allergic reaction. Investigations are still under way to elucidate the mechanism by which this novel protein amplify Ni allergy.

  15. Involvement with differentiation-inducing mechanism of Th17 and autophagy in oral mucosal leasions with erosive and ulcer

    SUGAWARA Yumiko, SAKAI Azusa, SUGAWARA Shunji, SASANO Takashi, SATO Kyoko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2011/04/28 - 2015/03/31

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    (Objective)Sogren's syndrome(SS) is an autoimmune disease that mainly affects the exocrine glands. On the other hand, sarcoidosis is a systemic granulomatous condition of unknown cause affecting multiple organs. The disease is characterized by the presence of noncaseating epithelioid cell granulomas and the most common sites are the lungs and lymph nodes. It can involve exocrine glands and, if salivary glands and lacrimal glands are affected, the disease can mimic SS. But there are extremely few reports that both diseases were histopathologically coexistent with labial salivary gland biopsy. Here, we report a case with coexistence of SS and sarcoidosis in order to analyze the clinical, immunologic, and histologic characteristics that may help physicians different the mimicry of SS by sarcoidosis from a true coexistence of both diseases. (Conclusion)We presented a case with coexistence of SS and sarcoidosis. She also had a finding of autoimmune hepatitis by the liver biopsy.

  16. Analysis of pathogenisis of metal allergy using humanized murine model

    SUGAWARA Shunji, KUROISHI Toshinobu, ENDO Yasuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Exploratory Research

    Institution: Tohoku University

    2012/04/01 - 2014/03/31

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    The aim of this study was to elucidate pathogenesis of metal allergy using humanized mice by reconstituting human immune system in the mice. We used genetically modified immunodeficient mice as recipients and tried to engraft human peripheral blood mononuclear cells in the mice. We also depleted macrophages in the mice to increase immunodeficiency. We observed very weak engraftment of human lymphocytes in the mice but are unable to induce metal allergy. As analysis of pathogenesis of metal allergy using humanized mice is still fascinating project to develop medical service for the next generation, we continue to realize this project.

  17. A study of mechanisms underlying oral mucous disease on helper T cells and innateimmunity.

    SUGAWARA YUMIKO, SAKAI Azusa, SUGAWARA Shunji, SASANO Takashi, ITOU Ayumi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2008 - 2010

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    IL-18 is a proinflammatory cytokine and plays an important pathogenic role in inflammatory and autoimmune disorders. IL-17 is also a proinflammatory cytokine and IL-17-secreting Th17 cells are involved in autoimmunity. The majority of the infiltrating cells in the salivary glands of SS patients were CD4^+T cells, and CD8^+T cells were infiltrated to a lesser extent. The predominant expression of IL-17 was found in infiltrating CD4^+T cells, whereas a small number of infiltrating CD8^+T cells expressed IL-17. Primary salivary gland cells from normal subjects partially confirmed these findings. These results suggest that IL-18 and Th17 cells detected in the salivary glands in SS patients are associated with the pathogenesis of SS in the salivary glands.

  18. 難治性口腔疾患成立における抗原提示細胞としての上皮細胞の役割

    菅原 俊二

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2009 - 2009

  19. in vivo analysis of HDC activity and cytokine productions by herpes virus group infections

    MONMA Yuko, SUGAWARA Shunji, ENDO Yasuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2007 - 2008

  20. Regulation of oral immunity and oral manifestation by a novel helper T cell subset

    SUGAWARA Shunji, KUROISHI Toshinobu, SUGAWARA Yumiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2007 - 2008

  21. 乳房炎乳汁中の催炎作用を示すラクトフェリン分子のヒト口腔内での催炎作用機構の解明

    小峯 健一, 黒石 智誠, 菅原 俊二, 小林 仁

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 萌芽研究

    Institution: 東北大学

    2006 - 2007

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    平成19年度においては、催炎性ラクトフェリン分子の合成ペプチドを作成し、ヒト口腔上皮株化細胞のHSC-1ならびにヒト腸管上皮株化細胞のCaco-2に対する刺激培養を行い、細胞内伝達因子の活性化に基づく炎症性サイトカインの産生誘導の増強を確認した。また、前記株化細胞を用い細胞膜の可溶化物質を作成し、催炎性ラクトフェリン分子に対する受容体をウェスタンブロッティング法により解析を行った。その結果、精製ラクトフェリンが反応しないが催炎性ラクトフェリン分子とは反応するバンドを確認することができ、現在、同定のためのアミノ酸配列解析用に必要な検体の作成中である。これら細胞株での受容体を同定後、然るべき時期に学会等での公表を行う予定である。なお、平成19年度においては、唾液中の催炎性ラクトフェリン分子の測定法について、その成果を公表しているが、本測定法はウシ乳汁中の催炎性ラクトフェリン分子の測定にも使用できることを確認している。 以上のように、本研究成果は乳製品の新たな品質管理指標となる可能性を示すとともに、ヒト口腔内や腸管における炎症の誘起や慢性化に何らかの働きを示している可能性を示唆するものと考えている。さらに本研究における成果は、国家的施策である「食の安全・安心運動」や「健康21運動」などを遂行する上で、食品として重要な位置づけをされている乳製品を提供する上で、今後重要な研究課題を提供することとなると推察される。

  22. Analysis of a murine nickel-allergy model promoted by endotoxin

    ENDO Yasuo, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2006 - 2007

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    2006: We found that endotoxin from gram-negative bacteria (or lipopolysaccharide, LPS) strongly promotes nickel (Ni)-allergy in the steps of both sensitization and elicitation, and we clarified the followings (published in Clin Exp Allergy 2007;37:743-751). 1. Inflammation was severer in Th1-dominant mice than in Th2-dominant mice. 2. Extent of inflammation in mice deficient in TNF or T cells was similar to that in control mice, while it was markedly weak in IL-1-deficient mice and in macrophage-depleted mice. 3. The activity of histamine-forming enzyme (HDC) increased in parallel with the progress of inflammation. 4. Inflammation tended to be augmented in mast cell-deficient mice, but markedly weak in HDC-deficient mice. 5. LPS also promoted the establishment of allergies to other metals (Cr, Co, Pd, Cu, and Ag). 2007: We found the followings (will be submitted after additional experiments) 1. In addition to macrophages, NK and/or basophiles may be involved in the development of Ni-allergy. 2. Ni-sensitized mice responded to Cr, Co, Pd, Cu, and Ag, too. 3. Histamine was involved in the process of elicitation. 4. In addition to LPS, other bacterial constituents or related inflammatory substances (MDP, mannan, polyI:polyC, or TLR2 ligands, concanavalin A, nitrogen-containing bisphosphonates) also promoted Ni-allergy in the steps of both sensitization and elicitation. 5. In the elicitation step, Ni, under the presence of LPS, induced inflammation at so low concentration as 1x10^<-12> M (i.e., inflammation may dramatically enhances the sensitivity to metal allergies).

  23. The research of the generation and mechanism for the lesion of the ulcer and erosion in oral mucosa

    SUGAWARA Yumiko, SHOUJI Noriaki, SUGAWARA Shunji, SASANO Takashi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2005 - 2007

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    Oral epithelial cells may form the first barriers of defense against oral bacteria in periodontal tissue. In this study, we thoroughly examined the expression of Toll-like receptor (TLR)2, TLR4, nucleotide-binding oligomerization domain (NOD)l and NOD2, and their possible antibacterial roles in terms of the expression of peptidoglycan recognition proteins (PGRPs) and b-defensin 2 in oral epithelial cells. 1) Oral epithelial cells constitutively express TLR2, TLR4, NOD1 and NOD2 molecules. 2) Oral epithelial cells do not secrete proinflammatory cytokines upon stimulation with synthetic PAMPs. 3) Synthetic PAMPs stimulated human oral epithelial cells to increase the expressions of four lands of PGRPs and b-defensin 2. 4) Up-regulation of PGRPs by Pam3CSSNA, lipid A, iE-DAP, and AMP were performed through TLR2, TLR4, NODI and NOD2, respectively. 5) The up-regulation of PGRPs induced by synthetic PAMPs was significantly inhibited in NF-kB p50- and p65-silenced cells. 6) Inflamed gingival epithelial cells clearly express PGRP proteins. 7) meso-DAP itself activates epithelial cells but not monocytic cells through NOD1.

  24. Immune regulation of oral mucosa and oral mucosal diseases by proteases and their inhibitors

    SUGAWARA Shunji, ENDO Yasuo, SUGAWARA Yumiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2005 - 2006

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    Research results of this project are as follows, 1. Trypsin-like protease produced by periodontopathic bacteria activated human gingival fibroblasts through protease activated receptor (PAR) 1 and PAR2, suggesting that this protease is critically involved in onset of periodontal disease. 2. Serum interleukin 18 (IL-18) levels and IL-18-dependent liver injury induced by LPS in Propionibacterium acnes-primed mice were significantly reduced by anti-Gr-1 injection (depletion of neutrophils). The same results were observed by co-administration of a serine protease inhibitor with LPS. A deficiency of PAR2 in mice significantly impaired IL-18 induction by treatment with P. acnes and LPS, and only slight pathological changes in hepatic tissues occurred in the PAR2^<-/-> mice treated with P. acnes and LPS. These results indicate that neutrophil recruitment and PAR2 activation by neutrophil serine proteases are critically involved in the induction of IL-18. 3. Lactoferrin (Lf) is an iron-binding antibacterial protein, present in most exocrine secretions, such as saliva. In this study, we identified small Lf peptides in the saliva of chronic periodontitis patients and confirmed them to be fragments of intact Lf. Proteinase 3 (PR3) protein was detected in the saliva of periodontitis patients, and PR3 activity and levels of Lf fragments were correlation to the severity of clinical symptoms. Saliva Lf peptides showed no anti-bacterial activity against Escherichia coil; and had a reduced iron-chelating capacity. Saliva Lf peptides induce the production of pro-inflammatory cytokines in human oral epithelial cells. These results suggest that Lf in the parotid saliva of periodontitis patients was degraded into small peptides by the PR3-like activity with the capability to induce inflammatory mediators. 4. We identified soluble form of Toll-like receptor 2 (TLR2) in saliva. As TLR2 is an originally transmembrane receptor, it is suggested that some proteases are involved in the generation of soluble TLR2. We found that saliva modulated the TLR2-mediated immune responses in oral cavity

  25. Analysis of Molecular and Biological Basis of Systemic Effects Provoked by Periodontal Diseases

    SHIMAUCHI Hidetoshi, KANAYA Sousuke, ITAGAKI Yumi, SUGAWARA Shunji, TAKAHASHI Nobuhiro, SHOJI Kanako

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku university

    2004 - 2006

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    The purpose of this study is to explore the unidentified "missing link" to connect the relationship between periodontal and systemic diseases by molecular biological approaches. For this purpose, we focused on the most potent pathogen of chronic periodontitis, Porphyromonas gingivalis and its components, and analyzed the molecular basis of exerting virulence of this bacterium on both periodontal lesions and bodies in vivo and in vitro. Using in vivo animal models, we investigated a series of studies clarifying ; 1)the role of P.gingivalis infection on hyperlipidemia in periodontitis patients ; 2)the effect of P.gingivalis virulence factors on production of adipocytokines from adipose tissues ; 3)the molecular effects of type 2 diabetes on the healing process of periodontium. First, our in vitro study revealed that P.gingivalis LPS and fimbriae preferentially induced a unique dendritic cell subset with a weak immunostimulatory activity via TLR2-mediated signaling, finally contributing to the immune escape of this bacterium in the periodontal lesion. Furthermore, in vivo studies indicated that infection of P.gingivalis is essential for up-regulation of serum triglycerides and its LPS down-regulated the serum level of adiponectin, suggesting P.gingivalis could exert its virulence after invasion into the systemic circulation. The concept of metabolic syndrome (MetS) has been evolving, that is a clustering of simple clinical measures including waist circumferences, blood pressure, triglycerides, high-density lipoproteins and glucose. This clustering appears depend on two major factors: excess body fat and metabolic susceptibility. Taken our results into this concept, invaded P.gingivalis may work as a MetS risk factor in periodontitis patients via down-regulating the serum adiponectin level. The increased risk of MetS possibly started the sequential of "Metaboic Domino" that increasing the susceptibility to diabetes and coronary heart diseases. Diabetes can delay the healing process of periodontally diseased tissue that may increase the chance of P.gigivalis invasion. In conclusion, P.gingivalis may have an adaptation system by dealing with the local immune defense that finally contributes to systemic-periodontal connection.

  26. Effect of IL-10 over-expression on bone resorption mechanism in apical periodontitis

    SHOJI Noriaki, SASANO Takashi, IIKUBO Masahiro, SUGAWARA Syunji, KOSEKI Kenyoshi, SAKAMOTO Maya

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2004 - 2005

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    Periapical bone resorption occurs following infection of the dental pulp. Bone destruction has been linked to excessive expression of inflammatory cytokines, particularly interleukin (IL)-1. IL-10 is an anti-inflammatory cytokine, produced by various immune cells including macrophages and T2 cells, that we previously found was a key endogeneous inhibitor of infection-stimulated peripheral bone resorption in vivo, likely acting via IL-1 inhibition. More recently, we have shown that IL-10^<-/-> mice are also extremely susceptible Porphyromonas gingivalis (Pg)-stimulated periodontal bone loss, without an increase in gingival IL-1 levels. In contrast, no significant bone loss is induced by the Pg infection in corresponding wild-type (WT) mice. In the present study, we will employ the IL-10^<+/+> mice model, a ‘reverse‘ model of IL-10^<-/-> mice, to test the hypothesis that induction and progression of apical periodontitis can be ameliorated by modulating IL-10, IL-10 receptors their signaling, and cytokine network that IL-10 regulates. The dental pulps of the first molars were exposed and infected with a mixture of four common endodontic pathogens, and bone destruction was determined by micro-computed tomography at sacrifice on day 21. The results demonstrate that IL-10^<+/+> mice model had no significantly greater infection-stimulated bone resorption in vivo compared with wild-type mice, although IL-10 in alveolar bone of them was over-expressed compared with that of wild-type mice.

  27. Novel bioactivities of neutrophil serine proteases against periodontopathic bacteria in innate immunity

    SUGAWARA Shunji, TAKADA Haruhiko, NEMOTO Eiji, ENDO Yasuo

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2003 - 2004

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    Research results of this project are as follows, 1.Neutrophil serine proteases (elastase, cathepsin G, and proteinase 3 (PR3)) activate human non-epithelial cells (i.e.human gingival fibroblasts (HGF)) through G-protein-coupled protease-activated receptor-2 (PAR-2) and induce cytokine production from the cells. PR3 but not elastase and cathepsin G activates oral epithelial cells, due to secretory leukocyte inhibitor (an inhibitor of elastase and cathepsin G but not PR3) from the epithelial cells. 2.Inflamed oral epithelium expresses PR3. Proinflammatory cytokines induce PR3 as membrane-bound and secretory forms with enzymatic activity. Antibodies to PR3 activate the cells through PAR-2 and induce chemokine production from the cells. 3.As T cells accumulate in the inflamed lamina propria of gingival tissue from patients with adult periodontitis, immune responses of gingival cells to T cell cytokines, interleukin-2 (IL-2) and IL-15 was investigated. Endogenous IL-15 expressed in HGF sustains recruitment of IL-2/15 receptor β and common γ through nuclear factor-κB activation in normal and inflamed HGF. 4.A trypsin-like proteases, gingipains, from periodontopathic bacteria cleave intercellular adhesion molecule-1 (CD54) expressed on oral epithelial cells, and consequently disrupt neutrophil-oral epithelial cell interaction. 5.SalivaCD14, an important molecule in innate immunity, promotes the invasion of oral epithelial cells by periodontopathic bacteria and consequently augments the production of chemokine, playing an important role in innate immunity in the oral cavity.

  28. Periodontal Diseases as a Hypersensitivity Reaction Based on Innate Immune Responses in Periodontal Tissues

    TAKADA Haruhiko, UEHARA Akiko, FUNAYAMA Hitomi, SUGAWARA Shunji, TADA Hiroyuki

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2002 - 2003

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    We performed studies based on the hypothesis that "in periodontal tissues in which numerous bacteria inhabit and interact with the cells, host defense systems, especially innate immune systems, are activated constitutively, resulting in hypersensitivity-like reactions leading to tissue destruction and periodontal diseases". The major findings were as follows. 1)Innate immune responses of oral epithelial cells : Human oral epithelial cells could not respond to endotoxic lipopolysaccharide [LPS; Toll-like receptor (TLR) 4 ligand], peptidoglycans (PGN; TLR2 ligand), and muramyldipeptide (MDP; intracellular receptor, NOD2 was discovered in the last year), while they responded to some cell-surface components of periodontopathic bacteria. Interferon-γ(IFNγ)-treated human oral epithelial cells responded to various bacterial components to produce inflammatoty cytokines. 2)Innate immune responses of fibroblasts in periodontal tissues : Human gingival fibroblasts carrying membrane CD14 (mCD14) responded to LPS, while human periodontal ligament fibroblasts carrying much TLR2 but lacking mCD14 could not respond. to LPS, but responded to PGN. IFNγ-treated human gingival. fibroblasts exhibited marked response to-various bacterial components, accompanied by up-regulation of mCD14 and Myd88, which is a common adaptor molecule for TLRs. Gingipains produced by Porphyroinonas gingivalis cleaved mCD14 on human gingival fibroblasts, resulting in hypo-responsiveness to. LPS. 3)Soluble CD14 (sCD 14) in human saliva : Human salivary gland cells, especially parotid gland cells, produced sCD14: The sCD14 concentration in parotid saliva was comparable to that in human serum. Salivary sCD14-augmented the incorporation of Actinobacillus actinomycetemcomitans by oral epithel oral cells, resulting in the enhancement of the innate immune responses of the cells. 4)TLR4 agonistic activity of fungal mannan : Fungal cell-wall mannan, including that from oral Candida albicans, activated human monocytic cells in a CD14-and TLR4-dependent manner.

  29. Regulation of oral mucosal immunity in human oral epithelial cells and periodontitis

    SUGAWARA Shunji, NEMOTO Eiji, TAKADA Haruhiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2001 - 2002

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    1. Oral epithelial cells constitutively express precursor form of interleukin-18 (IL-18) in the cells. Bioactive IL-18 was produced from the cells on costimulation with neutrophil serine proteinase, proteinase 3 (PR3), and Iipopolysaccharide (LPS) after interferon-γ (IFN-γ)-priming. PR3 was found to activate oral epithelial cells through G protein-coupled protease-activated receptor-2. 2. Oral epithelial cells do not express a bacterial pattern recognition receptor, CD 14, and express Toll-like receptors (TLRs)/MD-2/MyD88 system, which is critical in innate immune recognition. However, the cells are refractory to bacterial components even in the presence of soluble CD14, The cells are able to respond to components from black-pigmented bacteria (BPB). The cells acquire responsiveness to many bacterial components after priming with IFN-γ. 3. Nonendotoxic glycoprotein from BPB activates host cells in a CD14- and TLR2-dependent manner. 4. CD14-expreswsing human gingival fibroblasts (HGF) have the same property with oral epithelial cells. Human periodontal ligament fibroblasts (HPLF) express TLR2 more strongly than HGF. HGF mainly respond to Gram-negative, and HPLF mainly respond to Gram-positive bacterial components, respectively. Cysteine proteinases (gingipains) from periodontopafhic bacteria degrade CD14 on HGF, consequently, suppress CD14-dependent responsiveness to bacterial components. 5. Human salivary glands constitutively express CD14 and secrete as a soluble form in saliva.

  30. Inhibition of superantigen-induced apoptosis by LPS

    RIKIISHI Hidemi, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: TOHOKU UNIVERSITY

    2000 - 2001

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    Studies of the events triggered by bacterial superantigens provide rich insight into the constant battle between microbes and the immune system. In this study, we demonstrated a mechanism of apoptosis induced by staphylococcal enterotoxin B (SEB) in monocytes and some evidence for the anti-apoptotic function in CD80^+ monocytes. Pretreatment with pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-κB, resulted in significant reduction of the percentages of SEB-and IFN-γ (produced by SEB)-induced CD80^+ monocytes. Monocytes expressed constitutive NF-κB binding activity, and SEB and IFN-γ further activated NF-κB, which was inhibited by pretreatment with PDTC. Apoptosis of monocytes was enhanced by the addition of SEB. Increases in soluble CD95 ligand (sCD95L) levels were observed following stimulation with SEB, but not IFN-γ. Our results demonstrated that SEB treatment induced the activation of caspase-3 and -8, and pretreatment with z-VAD-fmk, a broad-spectrum inhibitor of caspases, prevented the induction of apoptosis at 24 h. CD80^- monocytes were sensitive to apoptosis, and survival of CD80^- monocytes from apoptosis by treating with z-VAD-fmk resulted in reduction of the percentages of CD80^+ monocytes. PDTC abolished anti-apoptotic function in those treated with IFN-γ. Thus, our results indicated that SEB stimulation includes both anti-apoptotic action through NF-κB activation by IFN-γ and pro-apoptotic action through sCD95L released by SEB, and that CD80 driven by NF-κB allows monocytes to participate in distinct survival programs and massive T-cell activation.

  31. Recognition of Cell-Surface Components of Bacteria in Innate Immune System, with Special Reference to the Role of Toll-Like Receptors

    TAKADA Haruhiko, NEMOTO Eiji, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    2000 - 2001

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    Toll-like receptors (TLR) are involved in the ability of the host innate immune system to recognize microbial patterns. We studied recognition of various bacterial components by the host innate immune system, especially cells in periodontal tissues, in relation to the pathogenesis of mucosal diseases in the oral cavity. We obtained the following findings, (l) Three cysteine proteases, gingipains, from periodontopathic Porphyromonas gingivalis cleaved membrane C 14 (mCD14) on human monocytes, leading to lipopolysaccharide (LPS) hyporesponsiveness of the cells. (2) Human leukocyte elastase cleaved mCD14 on human gingival fibroblasts (HGF), resulting in LPS hyporesponsiveness of the cells. (3) Gingival epithelial cells that lacked mCD14 did not respond to LPS, peptidoglycan (PGN), muramyldipeptide (MDP) which is a critical moiety of PGN, or lipoteichoic acids (LTA) from gram-positive bacteria even in the presence of soluble CD14 (sCD14) in contrast to the response of colonic epithelial cells. (4) Water-soluble PGN, SEPS, prepared from Staphylococcus epidermidis activated cells in a TLR2-dependent manner. When the glycan chain of SEPS was cleaved enzymatically, the TLR2-dependent activity of SEPS disappeared, and MDP was also inactive in this respect. (5) MDP activated human monocytic cells in a CD14- and TLR2-independent manner and up-regulated expression of MyD88, resulting in synergistic activation of the cells in combination with LPS or LTA, both of which are TLR4-dependent activators. (6) Interferon-γ primed HGF to increase response to LPS through up-regulation of mCD14 and MyD88 mRNA expression. Further studies are in progress in our laboratory to identify interactions between bacterial components and the host innate immune system in relation to pathogenesis of periodontal diseases.

  32. Analysis of endotoxin antagonism of lipoteichoic acids from oral streptococci

    SUGAWARA Shunji, TAKADA Haruhiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    1999 - 2000

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    1. Lipoteichoic acids (LTAs) of oral streptococci, Streptococcus sanguis and Streptococcus mutans, was shown to antagonize the activity of inflammatory cytokine production from CD14-positive human gingival fibroblasts (HGF) and human monocytes in response to endotoxin (LPS, lipopolysaccharide) and its active moiety, synthetic lipid A. 2. In addition to CD14 as a bacterial component receptor, Toll-like receptors (TLRs) transduce signals of the components into the cells. LTAs of other bacteria and LPS activated murine macrophages in a CD14/TLR2-and CD14/TLR4-dependent pathway, respectively, using gene knockout mice. 3. An well known LPS antagonist, a synthetic lipid A precursor (LA-14-PP) inhibited the function of CD14/TLR4 ligand (LPS) as well as CD14/TLR2 ligand (LTA) in human system, suggesting that CD14 is critically involved in the antagonism. 4. Binding of oral streptococcal LTAs to human monocytes was inhibited by anti-CD14 antibody and the LTAs binded to recombinant CD14 in a native-polyacrylamide gel electrophoresis, showing that the antagonism of the LTAs is mediated by competing with cell surface CD14. 5. Periodontal pathogenic Porphyromonas gingivalis cysteine proteinase (gingipain) and human neutrophil serine proteinase (elastase) preferentially proteolysed CD14 on human monocytes and HGF, resulting in down-modulation of LPS responsiveness of the cells.

  33. The etiological significance of superantigen in periodontal disease and its possible role

    RIKIISHI Hidemi, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: TOHOKU UNIVERSITY

    1998 - 1999

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    We demonstrated previously that superantigen (SAg) enhances CD80 expression on human monocytes, whereas treatment with SAg in the presence of lipopolysaccharide (LPS) markedly decreases the percentage of CD80ィイD1+ィエD1 peripheral blood monocytes, indicating that the presence of low levels of CD80 on monocytes inhibits CD27 expression on SAg-activated T cells due to insufficient delivery of positive signals via CD28/CD80 interaction. To assess the role of LPS in this inhibition, the relationship between SAg-dependent apoptosis and regulation of CD80 expression of CD14ィイD1+ィエD1 monocytes was examines. SAg enhanced the annexin V-positive or PI-positive (propidium iodide) levels in monocytes, whereas LPS-treated monocytes were resistant to the apoptotic action of SAg. This SAg-induced killing was abrogated by antagonists anti-CD95 (Fas) and anti-CD95 ligand monoclonal antibodies, suggesting a CD95-based pathway of apoptosis. Furthermore, apoptosis of monocytes, preferentially CD80ィイD1-ィエD1 monocytes, was affected by high-level expression of CD95 by SAg, and the survival required down-regulation of CD95 expression by LPS over the SAg action. During these culture periods, the number of CD80ィイD1+ィエD1 monocytes was nearly constant. These observations strongly suggested that a small fraction of CD80ィイD1+ィエD1 monocytes is selectively resistant to CD95-based apoptosis, and the percentage of CD80ィイD1+ィエD1 monocytes increases through escape from SAg-induced preferential apoptosis, which is inhibited by addition of LPS.

  34. Bacterial cell surface amphiphiles and periodontal diseases - Study on the role of CD14 molecule in periodontal tissues -

    TAKADA Haruhiko, NEMOTO Eiji, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: TOHOKU UNIVERSITY

    1998 - 1999

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    Bacterial cell surface amphiphiles exhibit various biological activities. Endotoxic lipopolysaccharides (LPS) distributed in the outer membrane of gram-negative bacteria and lipoteichoic acid (LTA) distributed in the cell surfaces of gram-positive bacteria are representative bioactive amphiphiles. Bacterial amphiphiles activate host cells such as macrophages through membrane CD14 (mCD14) expressed on cell surfaces. Last year, we demonstrated the presence of two types of human gingival fibroblasts that highly and lowly express mCD14, and the former cells produced interleukin-8 (IL-8) upon stimulation with LPS and lipid A from Enterobacteriaceae. This year, we found that 1. Bacillus subtilis LTA also activated human gingival fibroblasts via mCD14, whereas LTA from oral streptococci such as Streptococcus sanguis and Streptococcus mutans acted as an LPS-antagonist to inhibit IL-8-induction by LPS. 2. The LPS fraction from Prevotella intermedia, periodontal disease-associated bacteria, activated human dental pulp cells that lack mCD14, in a soluble CD14- and nuclear factor AP-1-dependent manner. 3. Furthermore, in collaboration with Prof. Shizuo Akira, Osaka University, we studied the relationship between amphiphiles and the Toll-like receptor (TLR) system, which was recently revealed to be associated with CD14 and is involved in LPS signaling. We revealed that LTA as well as LPS was recognized by TLR4 in contrast to previous reports. We also obtained evidence suggesting that a bioactive glycoprotein, PGP, prepared from P. intermedia, was recognized by TLR2. With the viewpoint that "bacterial products overstimulate the innate immune system, and result in tissue destruction," we would like to reveal how the CD14/TLR system recognizes and responds to microbes in periodontal tissues in relation to the pathogenesis of periodontal diseases.

  35. Activation of human gingival epithelial cells by black-pigmented bacteria

    SUGAWARA Shunji, SUGIYAMA Akiko, RIKIISHI Hidemi, TAKADA Haruhiko

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    1997 - 1998

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    1. Human gingival epithelial cells produce interleukin (IL)-8, granulocyte-colony stimulating factor and granulocyte-macrophage colony stimulating factor in response to Prevotella intermedia glycoprotein (PGP), and fimbriae andl ipopolysaccharide (LPS) fraction of Porphyromonas gingivalis. In contrast, the cells produce macrophage-colony stimulating factor stimulated with interferon (IFN)-gamma. 2. P.intermedia PGP, fimbriae and LPS fraction of P.gingivalis augmented the expression of intercellular adhesionmolecule-1 (ICAM-1) on the surface of human gingival epithelial cells, flow cytometically. 3. mRNA induction of the above cytokines and ICAM-1 in the cells by the components of black-pigmented bacteria (BPB)was confirmed by reverse-transcriptase PCR. 4. Human gingival epithelial cells do not express CD14, a major LPS receptor, which indicates that the cells are activated by the components of BPB with a distinct pathway from LPS of Enterobacteriaceae. In 1998, Toll-like receptors (TLRs)were reported to be signaling molecules of UPS, and also TLRs mediated LPS signal in a CD14-independent manner at a high concentration of LPS.The experiment that TLRs participate in the activation of human gingival epithelial cells by components of BPB is under way. 5. Human gingivalepithelial cells possess IL-18, a IFN-gamma inducing factor, in the cells as a possibly precursor form. Thes timulants used in this study could not induce the secretion of IL-18 by the cells. However, it is possible that IL-18produced by the cells with some stimulation, such as apoptotic pathway may induce IFN-gamma by immune cells, and that in turn, IFN-gamma produced may participate in the onset and cure of inflammation in periodontium.

  36. Inflammatory and anti-inflammatory actions of bisphosphonates, inhibitors of bone resorption

    ENDO Yasuo, KOSUGI Hirosi, SUGAWARA Shynji, NAKAMURA Masanori

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    1997 - 1998

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    Aminobisphosphonates (aminoBPs) are expected to be effective drugs for diseases with enhanced bone resorption. However, inflammatory side effects in their clinical applications are repeatedly reported. In the course of our studies on the histamine-forming enzyme (histidine decarboxylase, HDC), we found that these drugs induce abnormal inflammatory reactions in mice such as prolonged induction of HDC, increased number of granulocytic cells, exacerbation of experimental arthritis (a model of rheumatoid arthritis), etc. The aim of this project is to clarify the mechanism of the inflammatory actions of aminoBPs and we demonstrated the following : 1. AHBuBP, a typical aminoBP, augments both of the elevation of HDC activity and the production of IL-1 induced by LPS, but this agent suppresses the production of TNF induced by LPS.It was clarified that macrophages increased in mice given AHBuBP are responsible for the augmentation of IL-1 production in response to LPS. 2. Cl2MBP, a non-aminoBP, can suppress inflammatory reactions, elevation of HDC activity and augmentation of IL-1 production induced by aminoBPs. However, Cl2MBP did not suppress the elevation of HDC activity induced by LPS.Based on these results, we presented the idea that specific receptors for BPs might be present. (British Journal of Pharmacology, in press) 3. Both AHBuBP and LPS of Prevotella intermedia, a causative bacterium of periodontitis, elevate HDC activity in the mandible of mice. In addition, AHBuBP markedly augments the LPS-induced elevation of HDC activity in the mandible. (under submission) 4. IL-i-deficient mice, which were produced by using gene-targeting techniques, were provided Dr. Iwakura of Tokyo University. We found that inflammatory reactions, elevation of HDC activity and augmentation of IL-i production induced by aminoBPs are all abolished in the IL-1-deficient mice, indicating that IL-i mediates the inflammatory actions of aminoBPs. (in preparation) In this study, we clarified that IL-i mediates the inflammatory actions of aminoBPs. Our additional finding that the inflammatory actions of aminoBPs are almost completely prevented by Cl2MBP, a non-aminoBP, means that co-administration of an aminoBP and a non-aminoBP may be a useful clinical strategy to prevent inflammatory side effects of aminoBPs. In the next step of our study, it is important and interesting to clarify the biological meaning and the mechanism of this finding.

  37. Superantigen Produced by oral Streptococci and oral mucosal diseases.

    TAKADA Haruhiko, SUGIYAMA Akiko, HANAUMI Kiyoshi, SUGAWARA Shunji, RIKIISHI Hidemi

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (B)

    Institution: Tohoku University

    1996 - 1997

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    Takada et al.(J.Dent. Res., 75 : 922,1996) revealed that a superantigenic fraction F-2 from the culture ssupermatant of Streptococcus mits strain 108 endowed human peripheral blood T-cells with cytotoxic activity to human oral epithelial cells.The cytotoxic cell were mainly composed of CD8^+ cells. Pretreatment with human interferon gamma increased the sensitivity of epithelial cells to the cytotoxic of F-2-activated T-cells. The cytotoxic effects of the F-2-activated T-cells were mediated not by soluble factors as tumor necrosis factor, but the interaction between lymphocyte-function-associated amtigen-1 and intercellular adhesion molecule-1 (ICAM-1). Rikiishi et al.(FEMS Immounol. Med.Microbiol., 15 : 81,1996 & Immunology, 91 : 406,1997) isolated two novel superantigens from the supernatant of Streptococcus pyogenes type 12 strain, and designated as S.pyogenes mitogen (SPM) and mitogen-2 (SPM-2). SPM and SPM-2 had molecular weight 28,000 and 29,000, and isoelectric point (PI) of 9.2 and 6.0, respectively. Sugawara et al.(Clin.Exp.Immunol., 108 : 284,1997) examined the expression and up-regulation of cell adhesion molecles on a human colonic epithelial cell line HT-29, and the peripheral blood T lymphocyte proliferation responses to a staphylococcal superantigen SEB presentd by this cell line as compred with peripheral blood monocytes. They revealed that the superantigencic effects of SEB supported by HT-29 cells is an HLA-DR-and ICAM-1-dependent, but B7-2-and LFA-3-independent manner, whereas HLA-DR-, BF-2-, and LFA-3-dependent in the case supported by monocytes.

  38. Unusual increase of extrathymic T cells in the liver of autoimmune MRL-1pr/1pr mice.

    KUMAGAI Katsuo, HANAUMI Kiyoshi, RIKIISHI Hidemi, SUGAWARA Shunji

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for General Scientific Research (B)

    Institution: TOHOKU UNIVERSITY

    1993 - 1994

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    MRL/1pr mice, which are a model of SLE and rheumatoid arthritis in humans, develop profound lymphadenopathy resulting from the accumulation of CD3^+ 4^- 8^- double-negative (DN) alpha beta T cells in peripheral lymphoid tissues. We previously indicated that these DN alpha beta T cells preferentially proliferate in the liver and migrate to the periphery. In this study, we analyzed whether any kind of cytokine was produced by hepatic mononuclear cells (MNC) in MRL/1pr mice. The evidence obtained indicates that interleukin 6 (IL-6) was vigorously produced by hepatic MNC in diseased MRL/1pr mice under unstimulated conditions. MNC in the spleen of these mice produced small amounts of IL-6, while those in the lymph nodes did not produce any appreciable amounts of IL-6. These activities of hepatic MNC in diseased MRL/1pr mice were almost completely neutralized by anti-mouse IL-6 monoclonal antibody (mAb). On the other hand, immunohistochemical staining of light-and electron-microscopic analyzes revealed that the intracellular cell abhesion molecule 1 (ICAM-1) was expressed on the hepatic sinusoidal endothelial cells of diseased MRL/1pr mice. Moreover, ICAM-1 was newly induced in the hepatic sinusoids of control C3H/He mice by an intravenous injection of 50 units of recombinant mouse IL-6. These data suggest that ICAM-1 expressed on the hepatic sinusoidal endothelial cells in MRL/1pr mice is induced by IL-6, which is produced by hepatic MNC,and that such ICAM-1 may be responsible for the saturation of inflammatory cells and the proliferation of lymphocytes in the liver of MRL/1pr mice.

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