title: Inhibition of the expression of alpha-smooth muscle actin in human hepatic stellate cell line, LI90, by a selective cyclooxygenase 2 inhibitor, NS-398.
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.
authors.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
authors.forename: Jidong
authors.initials: J
authors.lastname: Cheng
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Imanishi
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.forename: Atara
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Noboru
authors.initials: N
authors.lastname: Ueki
authors.forename: Hideji
authors.initials: H
authors.lastname: Nakamura
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hada
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors*; D015153:Blotting, Western; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008099:Liver / Q000166:cytology*; D008565:Membrane Proteins; D009130:Muscle, Smooth / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000199:Actins; D024141:Collagen Type IV; D003470:Culture Media; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015850:Interleukin-6; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D006820:Hyaluronic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone