This study determined the role of nitric oxide (NO) on type I collagen expression in hepatic stellate cells. Inducible NO synthase (iNOS) mRNA and iNOS protein were detected in LX-2 cells, a human stellate cell line. INF-γ, which suppresses collagen expression, increased iNOS mRNA and iNOS protein, while acetaldehyde and TGFβ, which enhance collagen expression, decreased iNOS mRNA, but had no effect on iNOS protein. The NO donor DETANONOate diminished the stimulatory effect of TGBβ on α1(I) collagen mRNA and abrogated the enhancing effect of TGFβ on type I collagen protein. In conclusion, iNOS was detected in stellate cells under basal culture conditions. While in chronic models of hepatic fibrosis there is decreased hepatic fibrosis in iNOS-/- mice, this study shows that the immediate action of nitric oxide is to inhibit the enhancement by TGFβ of collagen expression by stellate cells.
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