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Studies of novel inhibitors of TLR signal

Research Project

Project/Area Number 22790421
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Bacteriology (including Mycology)
Research InstitutionNational Institute of Health Sciences

Principal Investigator

SUGIYAMA Kei-ichi  国立医薬品食品衛生研究所, 変異遺伝部変異遺伝部, 室長 (80356237)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsTLR / ペプチド / マイコトキシン / 敗血症
Research Abstract

Lipopolysaccharide (LPS) is a component of the membrane of Gram-negative bacteria, and a ligand for Toll-like receptor 4 (TLR4). LPS is generally considered to be a dominant pathogenic element in Gram-negative bacterial infection, and can lead to sepsis. Sepsis progresses to severe sepsis and septic shock. Around 750,000 cases of sepsis occur in the United States of America per year, and at least 225,000 of these are lethal. In spite of the high mortality rate, effective drugs to improve the lethality of sepsis have not been created. A peptide (STM28) which inhibited LPS-induced nuclear factor-κB activation in macrophage cells have isolated. In this study, it is revealed that STM28 has no effect on intracellular TLR-mediated signaling pathways. On the other hand, deoxynivalenol, trichothecene mycotoxin, inhibits the LPS-induced nitric oxide and interferon- β production. The present study also shows that this toxin inhibits MyD88-dependent pathway via TLR4. Moreover, I found that citrinin, which is a mycotoxin, down-regulates LPS signaling. These results suggest that STM28 and these toxins may have utility as a novel therapeutic agent for bacterial sepsis.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (10 results)

All 2012 2011 2010 Other

All Journal Article (2 results) Presentation (6 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] ペプチドによるエンドトキシン毒性の制御2012

    • Author(s)
      杉山圭一
    • Journal Title

      食品加工技術

      Volume: 32 Pages: 27-35

    • NAID

      40019579922

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Journal Article] 免疫毒性からみたマイコトキシン2012

    • Author(s)
      杉山圭一
    • Journal Title

      防菌防黴

      Volume: 40 Pages: 459-466

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] エンドトキシンとTLR リセ プター~ペプチドによる敗血症の治療 ~2012

    • Author(s)
      杉山圭一
    • Organizer
      第35回機能性食品用ペプチド研究会
    • Year and Date
      2012-08-21
    • Related Report
      2012 Final Research Report
  • [Presentation] カビ毒からみたグローバルレベルの環境変化と食の安全性~感染症とカビ毒の意外な関係~2011

    • Author(s)
      杉山圭一
    • Organizer
      日本食品科学工学会
    • Year and Date
      2011-09-10
    • Related Report
      2012 Final Research Report
  • [Presentation] カビ毒からみたグローバルレベルの環境変化と食の安全性2011

    • Author(s)
      杉山圭一
    • Organizer
      日本食品科学工学会
    • Place of Presentation
      東北大学(招待講演)
    • Year and Date
      2011-09-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] 敗血症治療薬としてのエン ドトキシンシグナル阻害分子に関する 研究(日本エンドトキシン・自然免疫 研究会奨励賞 受賞講演)2010

    • Author(s)
      杉山圭一
    • Organizer
      第16回日本エンドトキシン・自然免疫研究会
    • Year and Date
      2010-11-13
    • Related Report
      2012 Final Research Report
  • [Presentation] 敗血症治療薬としてのエンドトキシンシグナル阻害分子に関する研究2010

    • Author(s)
      杉山圭一
    • Organizer
      第16回日本エンドトキシン・自然免疫研究会(日本エンドトキシン・自然免疫研究会奨励賞受賞講演)
    • Place of Presentation
      かしはら万葉ホール
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] エンドトキシンとTLRリセプター~ペプチドによる敗血症の治療~

    • Author(s)
      杉山圭一
    • Organizer
      第35回機能性食品用ペプチド研究会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] 敗血症治療薬としてのエン ドトキシンシグナル阻害分子に関する 研究,エンドトキシン・自然免疫研究1 4-自然免疫と生体防御-福井博、谷徹、嶋田紘(編)2011

    • Author(s)
      杉山圭一
    • Publisher
      医学図書出版株式会社
    • Related Report
      2012 Final Research Report
  • [Book] 敗血症治療薬としてのエンドトキシンシグナル阻害分子に関する研究2011

    • Author(s)
      杉山圭一
    • Total Pages
      5
    • Publisher
      医学図書出版株式会社
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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