Smooth muscle alpha-actin expression in rat hepatic stellate cell is regulated by nitric oxide and cGMP production.
Mechanism by which lipopolysaccharide (LPS) and interferon gamma (IFN gamma) downregulate smooth muscle (SM) alpha-actin expression in rat hepatic stellate cell was studied. Culture-induced SM alpha-actin expression was suppressed in the presence of LPS (> 5 ng/ml) and/or IFN gamma (> 1 U/ml) dose-dependently. Inhibition of nitric oxide (NO) production by N omega-nitro-L-arginine (LNA) canceled such an inhibitory effect of LPS and/or IFN gamma. LPS and/or IFN gamma increased cellular level of cGMP in an LNA inhibitable manner, and cGMP analogues attenuated SM alpha-actin expression of the cells. These results indicate that NO-dependent increase of cellular cGMP level mediates the inhibitory effect of LPS and IFN gamma on SM alpha-actin expression in stellate cells.
Kawada
N
N
Department of Internal Medicine, Osaka City University Medical School, Japan.
Kuroki
T
T
Uoya
M
M
Inoue
M
M
Kobayashi
K
K
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D019335:Nitroarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP