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Graft Versus Host Disease

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

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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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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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