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.