Inhibition of the expression of alpha-smooth muscle actin in human hepatic stellate cell line,LI90, by a selective cyclooxygenase 2 inhibitor,NS-398 |
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Authors: | Cheng Jidong Imanishi Hiroyasu Liu Weidong Iwasaki Atara Ueki Noboru Nakamura Hideji Hada Toshikazu |
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Affiliation: | Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, 663, Hyogo, Japan. chjd@hyo-med.ac.jp |
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Abstract: | Cyclooxygenase 2 (COX-2) has been thought to be associated with liver fibrosis whereas it is well known that hepatic stellate cells (HSC) play a central role in the pathogenesis of liver fibrosis. There is little evidence of how COX-2 regulates the activation of human HSC or the mechanism involved. In this study, we investigated the effect of a COX-2 inhibitor, NS-398, on a line of human HSC, LI90. Our findings demonstrated that alpha-smooth muscle actin (alpha-SMA) protein expression was inhibited in a dose-dependent manner by treatment with NS-398. Proliferation cell nuclear antigen (PCNA) expression and cell growth were partially down-regulated. The generation of PGE2, IL-8, IL-6, and hyaluronan in the cultured medium was also inhibited. In conclusion, our findings imply that a selective COX-2 inhibitor might be a potential drug for the chemoprevention and treatment of liver fibrosis by inhibiting the activation of HSC. |
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