Cytokine‐induced expression of an inducible type of nitric oxide synthase gene in cultured vascular smooth muscle cells

In unstimulated cultured vascular smooth muscle cells (VSMC), mRNA of an inducible macrophage-type of nitric oxide synthase (iNOS) was barely detectable. Interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) markedly increased iNOS mRNA levels in time- and dose-dependent manners. The induction of iNOS mRNA paralleled the cytokine-induced nitrite production. Actinomycin D abolished the IFN gamma- and TNF alpha-induced increases in iNOS mRNA and nitrite production. Cycloheximide, which abolished both the IFN gamma- and TNF alpha-induced increases in nitrite production, had no effect on the IFN gamma-induced increase in iNOS mRNA but markedly inhibited the TNF alpha-induced one. These results suggest that IFN gamma directly induces the expression of the iNOS gene whereas TNF alpha mainly induces it via the induction of an intermediary protein in cultured VSMC.