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IgE-independent activation of mast cells

Research Project

Project/Area Number 16K08231
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto Pharmaceutical University (2018)
Okayama University (2016-2017)

Principal Investigator

Satoshi Tanaka  京都薬科大学, 薬学部, 教授 (40303846)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsマスト細胞 / Mrgpr / GPR35 / δ毒素 / アトピー性皮膚炎 / 蕁麻疹 / 脱顆粒応答 / AMPK / アレルギー・ぜんそく / 細胞・組織 / 生理活性 / 免疫学 / 薬学
Outline of Final Research Achievements

Accumulating evidence suggests that mast cells should be involved in various chronic inflammatory diseases including urticaria and atopic dermatitis in addition to immediate allergy such as pollen allergy and allergic asthma. However, it remains unknown how mast cells could trigger and exacerbate the chronic inflammatory diseases. Here, I clarified a part of the mechanism of mast cell activation induced by biogenic peptides, bacterial toxins, and polycations, which are different from IgE-mediated antigen stimulation. I, furthermore, identified a membrane protein that can suppress activation of mast cells in this study.

Academic Significance and Societal Importance of the Research Achievements

マスト細胞が病態形成に関わる炎症性疾患には決定的な治療法がないものも多く、近年注目されている抗体医薬による治療は費用面をはじめ患者への負担が大きい。本研究では、マスト細胞活性化の引き金に相当するステップに関わる分子、あるいはマスト細胞の活性化の抑制に関わる分子、およびそれらの機能を明らかにすることを通じて、低分子化合物による治療につながる基礎的知見を得ている。学術的には、機能が未知であるいくつかのGタンパク質共役型受容体の生理的機能の解明に貢献している。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017 2016 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Suppression of IgE-Independent Degranulation of Murine Connective Tissue-Type Mast Cells by Dexamethasone2019

    • Author(s)
      Yamada Keiko、Sato Hitomi、Sakamaki Kazuma、Kamada Mayumi、Okuno Yasushi、Fukuishi Nobuyuki、Furuta Kazuyuki、Tanaka Satoshi
    • Journal Title

      Cells

      Volume: 8 Issue: 2 Pages: 112-112

    • DOI

      10.3390/cells8020112

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of the minimal region of peptide derived from ADP-ribosylation factor1 (ARF1) that inhibits IgE-mediated mast cell activation2019

    • Author(s)
      Uchida Ryota、Egawa Tomonori、Fujita Yoshio、Furuta Kazuyuki、Taguchi Hiroaki、Tanaka Satoshi、Nishida Keigo
    • Journal Title

      Molecular Immunology

      Volume: 105 Pages: 32-37

    • DOI

      10.1016/j.molimm.2018.11.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of IFN-γ Production in Murine Splenocytes by Histamine Receptor Antagonists2018

    • Author(s)
      Kamei Miho、Otani Yukie、Hayashi Hidenori、Nakamura Tadaho、Yanai Kazuhiko、Furuta Kazuyuki、Tanaka Satoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 19 Issue: 12 Pages: 4083-4083

    • DOI

      10.3390/ijms19124083

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuromedin U directly induces degranulation of skin mast cells, presumably via MRGPRX22018

    • Author(s)
      Matsuo Yoshimi、Yanase Yuhki、Irifuku Reiko、Takahagi Shunsuke、Mihara Shoji、Ishii Kaori、Kawaguchi Tomoko、Tanaka Akio、Iwamoto Kazumasa、Watanuki Haruka、Furuta Kazuyuki、Tanaka Satoshi、Inoue Asuka、Aoki Junken、Hide Michihiro
    • Journal Title

      Allergy

      Volume: 73 Issue: 11 Pages: 2256-2260

    • DOI

      10.1111/all.13555

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 1-Fluoro-2,4-dinitrobenzene and its derivatives act as secretagogues on rodent mast cells.2017

    • Author(s)
      Manabe, Y., Yoshimura, M., Sakamaki, K., Inoue, A., Kakinoki, A., Hokari, S., Sakanaka, M., Aoki, J., Miyachi, H., Furuta, K., and Tanaka, S.
    • Journal Title

      Eur. J. Immunol.

      Volume: 47 Issue: 1 Pages: 60-67

    • DOI

      10.1002/eji.201646536

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vesicular Polyamine Transporter Mediates Vesicular Storage and Release of Polyamine from Mast Cells2017

    • Author(s)
      Tomoya Takeuchi, Yuika Harada, Satomi Moriyama, Kazuyuki Furuta, Satoshi Tanaka, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, and Miki Hiasa
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 292(9) Issue: 9 Pages: 3909-3918

    • DOI

      10.1074/jbc.m116.756197

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Down-modulation of antigen-induced activation of murine cultured mast cells sensitized with a highly cytokinergic IgE clone.2016

    • Author(s)
      Sakanaka M, Kurimune Y, Yamada K, Hyodo N, Natsuhara M, Ichikawa A, Furuta K, Tanaka S.
    • Journal Title

      Immunology letter

      Volume: 174 Pages: 1-8

    • DOI

      10.1016/j.imlet.2016.04.003

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Critical role of endogenous histamine in promoting end-organ tissue injury in sepsis.2016

    • Author(s)
      Hattori M, Yamazaki M, Ohashi W, Tanaka S, Hattori K, Todoroki K, Fujimori T, Ohtsu H, Matsuda N, Hattori Y.
    • Journal Title

      Intensive Care Med Exp.

      Volume: 4 Issue: 1 Pages: 36-44

    • DOI

      10.1186/s40635-016-0109-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 活性化マウスマスト細胞におけるIL-10産生の制御2019

    • Author(s)
      武内 雅志、山下 晶子、古田 和幸、田中 智之
    • Organizer
      第92回日本薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] IgE-independent degranulation of murine cutaneous mast cells2018

    • Author(s)
      Satoshi Tanaka
    • Organizer
      World Histamine Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Suppression of IgE-independent degranulation of murine mast cells by dexamethasone2018

    • Author(s)
      Satoshi Tanaka, Keiko Yamada, Kazuma Sakamaki, Hitomi Sato, Mayumi Kamada, Yasushi Okuno, Nobuyuki Fukuishi, Kazuyuki Furuta
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウスマスト細胞の成熟過程におけるデキサメタゾンの作用2016

    • Author(s)
      田中智之、山田圭位子、佐藤仁美、鎌田真由美、奥野恭史、福石信之、古田和幸
    • Organizer
      第89回日本生化学会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Presentation] IgE-independent activation of mast cells: An experimental contact allergen, 1-fluoro-2,4-dinitorbenzene is a mast cell secretagogue.2016

    • Author(s)
      Satoshi Tanaka
    • Organizer
      XVIth Meeting of Polish Histamine Research Society
    • Place of Presentation
      ウッチ(ポーランド)
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] IgE非依存的なマスト細胞活性化に対するデキサメタゾンの作用2016

    • Author(s)
      田中智之、山田圭位子、佐藤仁美、鎌田真由美、奥野恭史、福石信之、古田和幸
    • Organizer
      第20回日本ヒスタミン学会
    • Place of Presentation
      倉敷
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都薬科大学 薬理学分野

    • URL

      http://labo.kyoto-phu.ac.jp/yakuri/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 薬学部田中研究室:岡山大学

    • URL

      http://www.pharm.okayama-u.ac.jp/lab/meneki/

    • Related Report
      2017 Research-status Report 2016 Research-status Report
  • [Patent(Industrial Property Rights)] 複素環化合物又はその塩、GPR35作動薬及び医薬組成物2017

    • Inventor(s)
      松野研司、大野修、田中智之、古田和幸
    • Industrial Property Rights Holder
      松野研司、大野修、田中智之、古田和幸
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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