A Metalloproteinase Inhibitor Prevents Lethal Acute Graft-Versus-Host Disease in Mice-Reference-Cited by-同舟云学术

A Metalloproteinase Inhibitor Prevents Lethal Acute Graft-Versus-Host Disease in Mice

Published:1997-07-15 Issue:2 Volume:90 Page:542-548
ISSN:1528-0020
Container-title:Blood
language:en
Short-container-title:

Author:

Hattori Koichi¹,Hirano Takao¹,Ushiyama Chifuyu¹,Miyajima Hiroaki¹,Yamakawa Norifumi¹,Ebata Tomohiko¹,Wada Yukihisa¹,Ikeda Shoji¹,Yoshino Kohichiro¹,Tateno Masatoshi¹,Oshimi Kazuo¹,Kayagaki Nobuhiko¹,Yagita Hideo¹,Okumura Ko¹

Affiliation:

1. From the Division of Hematology and the Division of Rheumatology, the Department of Internal Medicine, the Division of Pathobiology, and the Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; the New Drug Discovery Research Laboratory, Kanebo Ltd, Osaka, Japan; and the Department of Pathology, Sapporo City General Hospital, Sapporo, Japan.

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 examined here the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-α and FasL release in a lethal acute GVHD model in mice. Administration of KB-R7785 into (BALB/c × C57BL/6) F1 that received C57BL/6 spleen cells markedly reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The ameliorating effect of KB-R7785 was superior to that of anti–TNF-α antibody. Our results suggest that KB-R7785 could be a potent therapeutic agent for GVHD.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

http://ashpublications.org/blood/article-pdf/90/2/542/235791/542.pdf

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