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.
MeSH terms
-
Actins / antagonists & inhibitors*
-
Blotting, Western
-
Cell Line
-
Collagen Type IV / metabolism
-
Culture Media / pharmacology
-
Cyclooxygenase 2
-
Cyclooxygenase 2 Inhibitors
-
Cyclooxygenase Inhibitors / pharmacology*
-
Dinoprostone / biosynthesis
-
Dose-Response Relationship, Drug
-
Down-Regulation
-
Extracellular Matrix / metabolism
-
Humans
-
Hyaluronic Acid / biosynthesis
-
Hyaluronic Acid / pharmacology
-
Interleukin-6 / biosynthesis
-
Interleukin-8 / biosynthesis
-
Isoenzymes / antagonists & inhibitors*
-
Liver / cytology*
-
Membrane Proteins
-
Muscle, Smooth / metabolism*
-
Nitrobenzenes / pharmacology*
-
Proliferating Cell Nuclear Antigen / biosynthesis
-
Prostaglandin-Endoperoxide Synthases
-
RNA, Messenger / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sulfonamides / pharmacology*
-
Time Factors
Substances
-
Actins
-
Collagen Type IV
-
Culture Media
-
Cyclooxygenase 2 Inhibitors
-
Cyclooxygenase Inhibitors
-
Interleukin-6
-
Interleukin-8
-
Isoenzymes
-
Membrane Proteins
-
Nitrobenzenes
-
Proliferating Cell Nuclear Antigen
-
RNA, Messenger
-
Sulfonamides
-
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
-
Hyaluronic Acid
-
Cyclooxygenase 2
-
PTGS2 protein, human
-
Prostaglandin-Endoperoxide Synthases
-
Dinoprostone