Differential effects of anti Fas ligand and MPI on GVHD pathologies

• Project/Area Number: 12557084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Hematology
• Research Institution: Juntendo 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: ¥4,100,000 (Direct Cost: ¥4,100,000); Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: HVG / 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) Fl 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

Research Products

• [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
• [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 graft-versus-host diseases."J. Immunol.. 167;9. 4981-4986 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] J,Sakurai, J,Ohata, K,Saito, H,Miyajima, T,Hirano, T,Kohsaka, S,Enomoto, K,Okumura, M,Azuma: "Blockade of CTLA-4 signals inhibits Th2-mediatei 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
• [Publications] K,Nozawa, J,Ohata, J,Sakurai, H,Hashimoto, H,Miyajima, H,Yagita, K,Okumura, M,Azuma: "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 graft-versus-host diseases."J Immunol. 167. 4981-4986 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [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)
• [Publications] Nozawa, K. et al.: "Preferential blockade of CD8+T cell responses by administration of anti-CD137 ligand moclonal antibody results in differential effect on development of murine acute chronic graft-versus-host disease"J. Immunol.. 167;9. 4981-4986 (2001)