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自己免疫疾患におけるLipid raftを介した細胞活性化の解析とその制御法の開発

Research Project

Project/Area Number 04F04244
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKanazawa Medical University

Principal Investigator

梅原 久範  金沢医科大学, 医学部, 教授

Co-Investigator(Kenkyū-buntansha) 金 哲雄  金沢医科大学, 医学部, 外国人特別研究員
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsリピッドラフト / アポトーシス / 全身性エリテマトーデス / スフィンゴミエリン / 自己免疫異常
Research Abstract

本研究は,全身性エリテマトーデスにおける免疫異常を細胞活性化シグナル伝達の中心である細胞膜lipid raft(ラフト)の面から明らかにすることにある.
基礎的検討として,ラフトのアポトーシスシグナルにおける重要性を検討した.このために,Fas発現WR19L細胞よりスフィンゴミエリン欠損株WR/Fas-SM(-)を樹立し,我々がクローニングしたsphingomyelin synthase gene (SMS-1) (J.B.C.279:18688-18693,2000)を遺伝子導入したスフィンゴミエリン合成回復株(WR/Fas-SMS1)を樹立した.両細胞におけるFas誘導アポトーシスの差異を検討した結果,Fas抗体架橋刺激により,SMS1細胞はSM(-)細胞に比べ,有意にFasの凝集,アポトーシスシグナルが誘導された.ラフトへのFasの移動およびラフトでのセラミド合成能は,WR/Fas-SMS1細胞で有意に増加していた.このことは細胞膜におけるスフィンゴミエリンが,ラフトの形成およびアポトーシスシグナル伝達に重要であることを示唆している.
臨床的検討として,全身性エリテマトーデス患者リンパ球のラフト発現の解析を行った.SLE患者T細胞およびB細胞ではラフト発現が有意に増強していることを認めた.さらに,T細胞分画では,制御性T細胞と思われるCD25陽性分画およびメモリーT細胞であるCD45陽性分画におけるラフト発現が著明に増強していた.これらのラフト発現増強はSLE患者における異常な免疫活性化と良く相関していた.このことは,SLEにおける自己反応性リンパ球がラフト発現により同定出来る可能性があること,このラフトを制御すれば自己免疫異常を制御出来る可能性を示唆している.

Report

(2 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004

All Journal Article (12 results)

  • [Journal Article] Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis2005

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

      J.Exp.Medicine 202

      Pages: 249-259

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis2005

    • Author(s)
      Miyaji, M., Jin, Z.-X., et al.
    • Journal Title

      J.Exp.Medicine 202

      Pages: 249-259

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interleukin-2-induced survival of natural killer(NK) cells involving phosphatidylinositol-3 kinase-dependent reduction of ceramide through acid sphingomyelinase, sphingomyelin synthase and glucosylceramide synthase.2004

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

      Blood 104

      Pages: 3285-3293

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells2004

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

      J.Biol.Chem. 279

      Pages: 18688-18693

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increase of nuclear ceramide through caspase-3-dependent regulation of the "sphingomyelin (SM) cycle" in Fas-induced apoptosis2004

    • Author(s)
      Watanabe I, et al.
    • Journal Title

      Cancer Res. 64

      Pages: 1000-1007

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fractalkine and vascular biology : from basic research to clinical diseases.2004

    • Author(s)
      Umehara H, et al.
    • Journal Title

      Arterio.Thromb.Vase.Biol.(Review). 24

      Pages: 34-40

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Anthracycline resistance in HL-60/ADR cells via transcriptional up-regulation of glucosylceramide synthase and reversal by Sp1 (GC-rich) decoy oligodeoxynucleotides.2004

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

      Cancer Res. 64

      Pages: 6271-6279

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Interleukin-2-induced survival of natural killer(NK) cells involving phosphatidylinositol-3 kinase-dependent reduction of ceramide through acid sphingomyelinase, sphingomyelin synthase and glucosylceramide synthase.2004

    • Author(s)
      Taguchi Y, Umehara H, et al.
    • Journal Title

      Blood 104

      Pages: 3285-3293

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells.2004

    • Author(s)
      Yamaoka S, Umehara H, et al.
    • Journal Title

      J.Biol.Chem 279

      Pages: 18688-18693

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Fractalkine and vascular biology : from basic research to clinical diseases.2004

    • Author(s)
      Umehara H, et al.
    • Journal Title

      Arterio.Thromb.Vasc.Biol 24

      Pages: 34-40

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increase of nuclear ceramide through caspase-3-dependent regulation of the "sphingomyelin (SM) cycle" in Fas-induced apoptosis2004

    • Author(s)
      Watanabe I, Umehara H, et al.
    • Journal Title

      Cancer Res. 64

      Pages: 1000-1007

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anthracycline resistance in HL-60/ADR cells via transcriptional up-regulation of glucosylceramide synthase and reversal by Sp1 (GC-rich) decoy oligodeoxynucleotides.2004

    • Author(s)
      Uchida Y, Umehara H, et al.
    • Journal Title

      Cancer Res 64

      Pages: 6271-6279

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2024-03-26  

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