Involvement of mast cell chymase in bleomycin-induced pulmonary fibrosis in mice.
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| Abstract |
The possible role of mast cell chymase in organ fibrosis was examined using a bleomycin-induced pulmonary fibrosis model in mice. Intratracheal injection of bleomycin to mice significantly increased not only hydroxyproline content but also chymase activity in the lung. Administration of a chymase inhibitor SUN C8077 (7-chloro-3-(3-amynophenyl) quinazoline-2, 4-dione methanesulfonate) dose-dependently reversed the bleomycin-induced increase in hydroxyproline content as well as chymase activity in the lung. Human chymase digested latent transforming growth factor-beta1 (TGF-beta1) to form mature TGF-beta1 in vitro, which was inhibited by SUN C8077. Human chymase, on the other hand, failed to stimulate DNA synthesis of human lung fibroblasts CCD-8Lu and LL97A. Taken together, it is suggested that mast cell chymase might participate in the pathogenesis of pulmonary fibrosis, and that the chymase-induced fibrosis might be mediated at least in part by TGF-beta1. Chymase inhibitor may be promising for treatment of pulmonary fibrosis in humans.
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| Authors | Yoshiaki Tomimori, Tsuyoshi Muto, Kayo Saito, Taisaku Tanaka, Hiroshi Maruoka, Motoo Sumida, Harukazu Fukami, Yoshiaki Fukuda |
| Journal | European journal of pharmacology (Eur J Pharmacol) Vol. 478 Issue 2-3 Pg. 179-85 (Oct 08 2003) ISSN: 0014-2999 [Print] Netherlands |
| PMID | 14575803 (Publication Type: Journal Article) |
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