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Purinergic signaling is a novel target of sepsis therapy

Research Project

Project/Area Number 24590125
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionTokyo University of Science

Principal Investigator

TSUKIMOTO Mitsutoshi  東京理科大学, 薬学部, 講師 (70434040)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords敗血症 / 炎症 / プリン受容体 / P2X7受容体 / P2Y11受容体 / ATP / サイトカイン / マクロファージ / 国際情報交換 スペイン / P2Y受容体 / 国際情報交換
Outline of Final Research Achievements

Sepsis is known as systemic inflammatory response syndorome (SIRS) with symptoms such as hypercytokinemi. Now, it is need to improve the therapy of sepsis. To establish effective therapy of sepsis, we investigated a role of purinergic signaling on sepsis by using immune cells and sepsis model mice in this study. We found that activation of P2Y11 receptor by exocytic ATP release in macrophage is involved in production of pro-inflammatory cytokine. P2Y11 receptor antagonist suppressed an increase of cytokine in LPS-treated mice. On the other hand, we also found that activation of P2X7 receptor play an important role in sepsis, suggesting that P2Y11 and P2X7 receptor antagonists would become a novel candidate of sepsis therapy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] Extracellular ATP induces P2X7 receptor activation in mouse Kupffer cells, leading to release of IL-1β, HMGB1, and PGE2, decreased MHC class I expression and necrotic cell death.2015

    • Author(s)
      Toki Y, Takenouchi T, Harada H, Tanuma S, Kitani H, Kojima S, Tsukimoto M.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 458(4) Issue: 4 Pages: 771-776

    • DOI

      10.1016/j.bbrc.2015.02.011

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Autocrine regulation of macrophage activation via exocytosis of ATP and activation of P2Y11 receptor.2013

    • Author(s)
      Sasaki H
    • Journal Title

      PLoS One

      Volume: 8 Issue: 4 Pages: e59778-e59778

    • DOI

      10.1371/journal.pone.0059778

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] P2X4 receptor regulates P2X7 receptor-dependent IL-1β and IL-18 release in mouse bone marrow-derived dendritic cells.2013

    • Author(s)
      Hayato Sakaki#, Takuya Fujiwaki#, Mitsutoshi Tsukimoto#*, Ayumi Kawano, Hitoshi Harada, Shuji Kojima. (# Co-first author, *corresponding author)
    • Journal Title

      BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

      Volume: 432(3) Issue: 3 Pages: 406-11

    • DOI

      10.1016/j.bbrc.2013.01.135

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ロキセチンによるP2X7受容体活性増強作用と炎症増悪化の可能性2015

    • Author(s)
      井山翔太、田沼靖一、月本光俊
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学、兵庫医療大学(兵庫県神戸市)
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨髄由来肥満細胞におけるP2X7受容体を介した炎症性サイトカイン産生2015

    • Author(s)
      久保木貴広、田沼靖一、月本光俊
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸学院大学、兵庫医療大学(兵庫県神戸市)
    • Year and Date
      2015-03-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨髄由来肥満細胞におけるP2X7受容体活性化の機能解析2014

    • Author(s)
      久保木貴広,小島周二,田沼靖一,月本光俊
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(東京都町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] パロキセチンによるP2X7受容体活性促進作用2014

    • Author(s)
      井山翔太,小島周二,田沼靖一,月本光俊
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(東京都町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肝マクロファージ/kupffer細胞におけるP2X7受容体の機能解析2014

    • Author(s)
      土岐勇介,小島周二,竹之内敬人,木谷 裕, 田沼靖一,月本光俊
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(東京都町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] セプシスモデルマウスへのP2X7受容体阻害薬の効果2014

    • Author(s)
      田中里美, 月本光俊,PELEGRIN Pablo, 原田均, 小島周二
    • Organizer
      日本薬学会134年会
    • Place of Presentation
      熊本市
    • Related Report
      2013 Research-status Report
  • [Presentation] ATP開口放出とP2Y11受容体活性化を介した新規マクロファージ活性化機構

    • Author(s)
      月本光俊、榊隼人、原田均、森山芳則、小島周二
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Research-status Report
  • [Presentation] セプシス病態におけるP2X7受容体の関与

    • Author(s)
      田中 里美,月本 光俊,PELEGRIN Pablo, 原田 均,小島 周二
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Research-status Report
  • [Presentation] Regulation of P2X7 Receptor-Mediated Inflammatory Functions by Co-expression of P2X4 Receptor in Macrophages

    • Author(s)
      月本光俊、原田均、小島周二
    • Organizer
      第86回 日本薬理学会年会
    • Place of Presentation
      福岡県博多市
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] セプシスにおけるP2X7受容体の関与

    • Author(s)
      田中里美、月本光俊、小島周二
    • Organizer
      第56回日本薬学会関東支部大会
    • Place of Presentation
      千葉県昭和大学
    • Related Report
      2012 Research-status Report
  • [Presentation] Extracellular nucleotides-mediated autocrine/paracrine signaling (Purinergic Signaling)

    • Author(s)
      Mitsutoshi Tsukimoto
    • Organizer
      1st INTERNATIONAL POSTGRADUATE CONFERENCE ON PHARMACEUTICAL SCIENCES 2012 (iPoPS 2012)
    • Place of Presentation
      クアラルンプール(マレーシア)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Regulation of P2X7 Receptor-Mediated Inflammatory Functions by Coexpression of P2X4 Receptor in Mouse Macrophages

    • Author(s)
      Mitsutoshi Tsukimoto, Ayumi Kawano, Taisei Noguchi, Daisuke Mori, Noriyuki Hotta, Hitoshi Harada, Takato Takenouchi, Hiroshi Kitani, Shuji Kojima
    • Organizer
      Purine2012
    • Place of Presentation
      福岡県博多市
    • Related Report
      2012 Research-status Report
  • [Presentation] Involvement of Purinergic Signaling via Exocytosis in Cytokine Production by Activated Macrophages

    • Author(s)
      Hayato Sakaki, Mitsutoshi Tsukimoto, Hitoshi Harada, Yoshinori Moriyama, Shuji Kojima
    • Organizer
      Purine2012
    • Place of Presentation
      福岡県博多市
    • Related Report
      2012 Research-status Report
  • [Remarks] 月本光俊 研究室紹介 東京理科大学

    • URL

      http://www.tus.ac.jp/fac_grad/p/index.php?4d1d

    • Related Report
      2014 Annual Research Report
  • [Remarks] 月本光俊 研究内容

    • URL

      http://www.tus.ac.jp/fac_grad/p/intro.php?4d1d

    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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