AI Article Synopsis
- The study investigated the role of mast cell chymase in pulmonary fibrosis using a mouse model induced by bleomycin.
- The injection of bleomycin increased both chymase activity and hydroxyproline levels in the lungs, and a chymase inhibitor significantly reduced these effects.
- The findings suggest that chymase may contribute to pulmonary fibrosis via transforming growth factor-beta1 (TGF-beta1), indicating that chymase inhibitors could be a potential treatment for this condition in humans.
Article 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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| http://dx.doi.org/10.1016/j.ejphar.2003.08.050 | DOI Listing |
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