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2005 Fiscal Year Final Research Report Summary

Roles for MD molecules in endotoxin recognition

Research Project

Project/Area Number 14021012
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

MIYAKE Kensuke  The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (60229812)

Project Period (FY) 2002 – 2005
Keywordsendotoxin / Toll-like receptor / innate immunity
Research Abstract

Little is known about mechanisms underlying microbial recognition in the innate immune system. Toll-like receptors (TLR) sense the presence of pathogens and trigger defense responses by transducing activating signals. This project focuses on endotoxin (LPS, lipopolysaccharide) recognition and aim to reveal molecular mechanism for LPS recognition. We previously discovered MD-2 that is associated with TLR4 and indispensable for LPS responses by TLR4. Further, we showed direct interaction between LPS and the receptor complex consisting of TLR4 and MD-2 (TLR4/MD-2). We next focused on the event following ligand interaction with TLR4/MD-2, oligomerization of TLR4/MD-2. Further, antagonistic lipid A analogue lipid IVa was found to bind to TLR4/MD-2 but not to induce oligomerization. These results suggest that LPS responses are triggered not by ligand binding but by the following receptor oligomerization. MD-2 has a critical role in triggering TLR4/MD-2 oligomerization. LPS, a ligand to TLR4/MD-2 is not homogenous but differ in its structure with Gram-negative bacteria. TLR4/MD-2 is able to discriminate such a difference in structure between bacteria and MD-2 has a critical role in the discrimination.

  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression.2006

    • Author(s)
      今野和典
    • Journal Title

      Biochem Biophys Res Commun 339

      Pages: 1076-1082

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Agonistic Antibody to Toll-like receptor 4/MD-2 Protects Mice from Acute Lethal Hepatitis Induced by Tumor Necrosis Factor-α2006

    • Author(s)
      赤司祥子
    • Journal Title

      Journal of Immunology 176

      Pages: 6211-6218

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulatory Roles for MD-2 and Toll-like receptor 4 (TLR4) in Ligand-induced Receptor Clustering.2006

    • Author(s)
      小林真紀子
    • Journal Title

      Journal of Immunology 176

      Pages: 4244-4251

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A Protein Associated with Toll-like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4.2006

    • Author(s)
      若林靖隆
    • Journal Title

      Journal of Immunology 177

      Pages: 1772-1779

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression.2006

    • Author(s)
      Konno K, et al.
    • Journal Title

      Biochem Biophys Res Commun. 339

      Pages: 1076-1082

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Agonistic Antibody to Toll-like receptor 4/MD-2 Protects Mice from Acute Lethal Hepatitis Induced by Tumor Necrosis Factor-a2006

    • Author(s)
      Akashi-Takamura S, et al.
    • Journal Title

      J. Immunol. 176

      Pages: 4244-4251

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulatory Roles for MD-2 and Toll-like receptor 4 (TLR4) in Ligand-induced Receptor Clustering.2006

    • Author(s)
      Kobayashi M, et al.
    • Journal Title

      J. Immunol. 176

      Pages: 6211-6218

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A Protein Associated with Toll-like Receptor 4 (PRAT4A) Regulates Cell Surface Expression of TLR4.2006

    • Author(s)
      Wakabayashi Y, et al.
    • Journal Title

      J. Immunol. 177

      Pages: 1772-1779

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The Radioprotective 105/MD-1 Complex Links Toll-like Receptor 2 (TLR2) and TLR4/MD-2 in Antibody Response to Microbial Membranes.2005

    • Author(s)
      長井良憲
    • Journal Title

      Journal of Immunology 174

      Pages: 7043-7049

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The Radioprotective 105/MD-1 Complex Links Toll-like Receptor 2 (TLR2) and TLR4/MD-2 in Antibody Response to Microbial Membranes2005

    • Author(s)
      Nagai Y, et al.
    • Journal Title

      J. Immunol. 174

      Pages: 7043-7049

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization.2004

    • Author(s)
      斉藤 伸一郎
    • Journal Title

      International Immunology 16

      Pages: 961-969

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization.2004

    • Author(s)
      Saitoh, S., et al.
    • Journal Title

      Int Immunol. 16

      Pages: 961-969

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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