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Differential effects of anti Fas ligand and anti TNF-alpha antibodies on GVHD pathologies

Research Project

Project/Area Number 12671005
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionJuntendo University

Principal Investigator

HIRANO takao  Juntendo University school of medicine Dept. of Internal medicine Associate professor, 医学部, 助教授 (10165186)

Co-Investigator(Kenkyū-buntansha) YAGITA hideo  Juntendo University school of medicine Dept. of Immunology Associate professor, 医学部, 助教授 (30182306)
OSHIMI kazuo  Juntendo University school of medicine Dept. of Internal medicine Professor, 医学部, 教授 (40089991)
MIYAJIMA hiroaki  Juntendo University school of medicine Div. of Pathobiology Assistant professor, 医学部, 助手 (80209907)
OKUMURA ko  Juntendo University school of medicine Dept. of Immunology Professor, 医学部, 教授 (50009700)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsHVG / GVH / metalloproteinase inhibitor / GVL / TNF-alpha / Fas / FasL / GVHD / MPI / HVGD / IL-4 / メタロプロテナーゼインヒビター
Research Abstract

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), that is a major complication after allogeneic bone marrow transplantation. We here examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 into irradiated (BALB/c x C57BL/6) F1 mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The KB-R7785 treatment did not affect the hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.

Report

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

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Sakurai, J. et al.: "Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells"J. Immunol.. 164;2. 664-669 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nozawa, K. et al.: "Preferential blockade of CD8+ T Cell responses by administration of anti-CD137 ligand monoclonal antibody results in differential effect on development of murine acute and chronic"J. Immunol.. 167;9. 4981-4986 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] J. Sakurai, J. Ohata, K. Saito, H. Miyajima, T. Hirano, T. Kohsaka, S. Enomoto, K. Okumura, and M. Azuma: "Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells"J. Immunol. 164. 664-669 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Nozawa, J. Ohata, J. Sakurai, H. Hashimoto, H. Miyajima, H. Yagita, K. Okumura, and M. Azuma: "Preferential blockade of CD8(+) T cell responses by administration of anti-CD 137 ligand monoclonal antibody results in differential effect on development of murine acute and chronic graft-versus-host diseases"J Immunol. 167. 4981-4986 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakurai, J., et al.: "Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells"J.Immunol.. 164;2. 664-669 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nozawa, K., et al.: "Preferential blocade of CD8+T cell responses by administration of anti-CD137 ligand moclonal antibody result in differential effect on development of murine acute and chronic graft-versus-host disease"J.Immunol.. 167;9. 4981-4986 (2001)

    • Related Report
      2002 Annual Research Report

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

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