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

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Abstract
In unstimulated cultured vascular smooth muscle cells (VSMC), mRNA of an inducible macrophage-type of nitric oxide synthase (iNOS) was barely detectable. Interferon γ (IFNγ) and tumor necrosis factor α (TNFα) 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 IFNγ- and TNFγ-induced increases in iNOS mRNA and nitrite production. Cycloheximide, which abolished both the IFNγ- and TNFα-induced increases in nitrite production, had no effect on the IFNγ-induced increase in iNOS mRNA but markedly inhibited the TNFα-induced one. These results suggest that IFNγ directly induces the expression of the iNOS gene whereas TNFα mainly induces it via the induction of an intermediary protein in cultured VSMC.