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Analysis of the mechanism of membranous proteolysis and the immunoregulation for Sjogren's syndrome

Research Project

Project/Area Number 12307040
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionThe University of Tokushima

Principal Investigator

HAYASHI Yoshio  The University of Tokushima, School of Dentistry, Department of Pathology, Professor, 歯学部, 教授 (00127854)

Co-Investigator(Kenkyū-buntansha) 斎藤 一郎  徳島大学, 歯学部, 助教授 (60147634)
柳 久美子  徳島大学, 歯学部, 助手 (90294701)
羽地 則雄  徳島大学, 歯学部, 助手 (30274228)
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥42,540,000 (Direct Cost: ¥37,500,000、Indirect Cost: ¥5,040,000)
Fiscal Year 2003: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2002: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2001: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2000: ¥20,700,000 (Direct Cost: ¥20,700,000)
KeywordsSjogren's syndrome / Apoptosis / Caspase / Autoantigen / α-fodrin / Fas Ligand / AICD / Estrogen-deficiency / アナログペプチド / 末梢トレランス / α-fodrin / deletin mutagenesis法 / 実験的治療 / 膜骨格タンパク / 自己反応性T細胞
Research Abstract

Primary Sjogren's syndrome is an autoimmune disorder characterized by lymphocytic infiltrates and destruction of the salivary and lacrimal glands, and systemic production of autoantibodies to the ribonucleoprotein (RNP) particles SS-A/Ro and SS-B/La. The purpose of this research is to elucidate the mechanisms on the development of primary Sjogren's syndrome. Although several candidate autoantigens including α-fodrin have been reported in Sjogren's syndrome, the pathogenic roles of the autoantisens in initiation and progression of SS are still unclear. It is possible that individual T cells activated by an appropriate self antigen can proliferate and form a restricted clone. Recent evidences suggest that the apoptotic pathway plays a central role in tolerazing T cells to tissue-specific self antigen, and may drive the autoimmune phenomenon. Cleavage of certain autoantigens during apoptosis may reveal immunocryptic epitopes that could potentially induce autoimmune response. The studies reviewed imply that Fas-mediated cytotoxicity and caspase-mediated α-fodrin proteolysis are involved in the progression of tissue destruction in Sjogren's syndrome. Fas ligand (FasL), and its receptor Fas are essential in the homeostasis of the peripheral immune system. It can be considered that a defect in activation-induced cell death (AICD) of effector T cells may result in the development of autoimmune exocrinopathy in Sjogren's syndrome. Although the mechanisms by which estrogen deficiency influences autoimmune lesions remain unclear, it is possible that antiestrogenic actions might be a potent factor in the formation of pathogenic autoantigens

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Hayashi Y, Arakaki R, Ishimaru N.: "Apoptosis, and estrogen deficiency in primary Sjogren's syndrome."Cur.Opin.Rheumatol. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoneda T, et al.: "Estrogen deficiency accelerates murine autoimmune arthritis associated with RANKL-mediated osteoclastogenesis."Endocrinol.. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishimaru N, et al.: "Development of autoimmune exocrinopathy resembling Sjogren's syndrome in estrogen-deficient mice of healthy background."Am.J.Pathol.. 163. 1481-1490 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katunuma N, et al.: "Insights into the roles of cathepsins in antigen processing and presentation revealed by specific inhibitors."Biol.Chem.. 348. 883-890 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi Y, Arakaki R, Ishimaru N.: "The role of caspase cascade on the development of primary Sjogren's syndrome."J.Med.Invest.. 50. 32-38 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arakaki R, et al.: "Development of autoimmune exocrinopathy resembling Sjogren's syndrome in adoptively transferred mice with autoreactive CD4^+ T cell."Arthritis Rheum.. 48. 3603-3609 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa K, et al.: "Anti-α-fodrin autoantibodies in Moyamoya disease."Stroke. 34. 244-246 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi Y Arakaki R, Ishimaru N.: "Apoptosis, and estrogen deficiency in primary Sjogren's syndrome"Cur.Opin.Rheumatol. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoneda T, et al.: "estrogen deficiency accelerates murine autoimmune arthritis associated with RANKL-mediated osteoclastogenesis"Endocrinol.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishimaru N, et al.: "Development of autoimmune exocrinopathy resembling Sjogren's syndrome in,, estrogen-deficient mice of healthy thy ground"Am.J.Pathol.. 163. 1481-1490 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katunuma N, et al.: "Insights into the roles of cathepsins in antigen processing and presentation revealed by s specific inhibitors"Biol Chem.. 384. 883-890 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi Y, Arakaki, R., Ishimaru N.: "The role of caspase cascade on the development of primary Sjogren's syndrome"J.Med.Invest.. 50. 32-38 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arakaki R, et al.: "Development of autoimmune exocrinopathy 2-esembling Sjogren's syndrome in adoptively transferred mice with autoreactive CD4^+ T cell"Arthritis Rheum. 48. 3603-3609 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogawa K, et al.: "Anti-α-fodrin autoantibodies in Moyamoya disease"Stroke. 34. 244-246 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hayashi Y, Arakaki R, Ishimaru N.: "Apoptosis, and estrogen deficiency in primary Sjogren's syndrome"Cur.Opin.Rheumatiol. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoneda T, et al.: "Estrogen deficiency accelerates murine autoimmune arthritis associated with RANKL-mediated osteoclastogenesis"Endocrinol.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishimaru N, et al.: "Development of autoimmune exocrinopathy resembling Sjogren's syndrome in estrogen-deficient mice of healthy background"Am.J.Pathol.. 163. 1481-1490 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Katunuma N, et al.: "Insights into the roles of cathepsins in antigen processing and presentation revealed by specific inhibitors"Biol.Chem.. 348. 883-890 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hayashi Y, Arakaki R, Ishimaru N.: "The role of caspase cascade on the development of primary Sjogren's syndrome"J.Med.Invest.. 50. 32-38 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arakaki R, et al.: "Development of autoimmune exocrinopathy resembling Sjogren's syndrome in adoptively transferred mice with autoreactive CD4^+ T cell"Arthritis Rheum.. 48. 3603-3609 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogawa K, et al.: "Anti-α-fodrin autoantibodies in Moyamoya disease"Stroke. 34. 244-246 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hayashi Y et al.: "The role of caspase cascade on the development of primary Sjogren's syndrome"J. Med. Invest.. 50. 32-38 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saegusa K et al.: "Cathepsin S-inhibitor prevents autoantigen presentation and autoimmunitv"J. Clin. Invest.. 110. 361-369 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saegusa K et al.: "Prevention and induction of autoimmune exocrinopathy is dependent on pathogenic autoantigen cleavage in murine Sjogren's syndrome"J. Immunol.. 169. 1050-1057 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Azuma M et al.: "Suppression of TNF-α-induced MMP 9 production in human salibary gland acinar cells by cepharanthine occurs via downregulation of NFkB"Arthritis Rheum.. 46. 1585-1594 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishimaru N et al.: "possible role of organ-specific autoantigen for activation-induced cell death in murine Siogren's syndrome"J. Immunol.. 167. 6031-6037 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue H et al.: "Possible involvement of Epstein-Barr virus mediated α-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome"J. Immunol.. 166. 5801-5809 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsubota, K. et al.: "Functional recovery by topical application of cyclosporin A in Siogren's svndrome mouse model"Invest. Ophthal. Vis. Sci.. 42. 101-110 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue, H. et al.: "Possible involvement of Epstein-Barr virus mediated α-fodrin cleavage for organ-specific autoantigen in Sjogren's svndrome"J. Immunol.. 166. 5801-5809 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi, I. et al.: "Anti-α-fodrin autoantibody is an early diagnostic marker for childhood primarv Sjogren's svndrome"J. Rheumatol.. 28. 363-365 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Maeno, N. et al.: "Anti-α-fodrin antibodies in Sjogren's syndrome in chirldren"J. Rheumatol.. 28. 860-864 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishimaru, N. et al.: "Possible role of organ-specific autoantigen for Fas ligand-mediated activation-induced cell death in murine Sjogren's syndrome"J. Immunol.. 167. 6031-6037 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Azuma, M. et al.: "Cepharantine suppresses tumor necrosis tactor-α-induced matrix metalloproteinase-9-production by downregulating nuclear factor kB in human salivary gland acinar cells"Arthritis Rheum.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kaoru Saegusa et al.: "Treatment with anti-CD86 costimulatory molecule prevents the autoimmune lesions in murine Siogren's syndrome (SS) through up-regulated Th2 response"Clin.Exp.Immunol.. 119. 354-360 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshio Hayashi et al.: "Involvement of apoptotic protease cascade for tissue destruction in Sjogren's syndrome."Arch.Immunol.Ther.Exp.. 48. 399-403 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Naozumi Ishimaru et al.: "Severe destructive autoimmune lesions with aging in murine Sjogren's syndrome through Fas-mediated apoptosis."Am.J.Pathol.. 156. 1557-1564 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaoru Saegusa et al.: "Mechanisms of neonatal tolerance induced in an animal model for primary Sjogren's syndrome by intravenous administration of autoantigen."Scand.J.Immunol.. 52. 264-270 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kaoru Saegusa et al.: "Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy in murine Sjogren's syndrome"J.Immunol.. 165. 2251-2257 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hideki Nakamura et al.: "Expression and function of X chromosome-linked inhibitor of apoptosis protein in Sjogren's syndrome"Lab.Invest.. 80. 1421-1427 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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