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Graft Versus Host Disease

A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation

Bone Marrow Transplantation volume 23, pages 1283–1289 (1999)Cite this article

Abstract

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft- versus-host disease (GVHD), which is a major complication after allogeneic bone marrow transplantation. We have examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-α and FasL release in a murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 to irradiated (BALB/c × 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 hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation.

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Authors and Affiliations

  1. Division of Hematology, Juntendo University School of Medicine, Tokyo, Japan

    K Hattori, T Hirano & K Oshimi

  2. Division of Rheumatology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan

    C Ushiyama

  3. Division of Pathobiology, Juntendo University School of Medicine, Tokyo, Japan

    H Miyajima

  4. Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan

    N Yamakawa, N Kayagaki, H Yagita & K Okumura

  5. New Drug Discovery Research Laboratory, Kanebo Ltd, Osaka, Japan

    S Ikeda & K Yoshino

  6. Department of Pathology, Sapporo City General Hospital, Sapporo, Japan

    M Tateno

  7. CREST (Core Research for Evolutional Science and Technology) of Japan Science and Technology Corporation (JST), Tokyo, Japan

    H Yagita & K Okumura

Authors
  1. K Hattori
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  2. T Hirano
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  3. C Ushiyama
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  4. H Miyajima
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  5. N Yamakawa
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  6. S Ikeda
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  7. K Yoshino
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  8. M Tateno
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  9. K Oshimi
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  10. N Kayagaki
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  11. H Yagita
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  12. K Okumura
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Cite this article

Hattori, K., Hirano, T., Ushiyama, C. et al. A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation. Bone Marrow Transplant 23, 1283–1289 (1999). https://doi.org/10.1038/sj.bmt.1701792

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  • DOI: https://doi.org/10.1038/sj.bmt.1701792

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