Koide M, Kawahara Y, Tsuda T, Yokoyama M
Department of Internal Medicine (1st Division), Kobe University School of Medicine, Japan.
FEBS Lett. 1993 Mar 8;318(3):213-7. doi: 10.1016/0014-5793(93)80514-u.
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.
在未受刺激的培养血管平滑肌细胞（VSMC）中，几乎检测不到诱导型巨噬细胞一氧化氮合酶（iNOS）的mRNA。γ干扰素（IFNγ）和肿瘤坏死因子α（TNFα）以时间和剂量依赖的方式显著增加iNOS mRNA水平。iNOS mRNA的诱导与细胞因子诱导的亚硝酸盐产生平行。放线菌素D消除了IFNγ和TNFα诱导的iNOS mRNA和亚硝酸盐产生的增加。环己酰亚胺消除了IFNγ和TNFα诱导的亚硝酸盐产生的增加，对IFNγ诱导的iNOS mRNA增加没有影响，但显著抑制了TNFα诱导的增加。这些结果表明，IFNγ直接诱导iNOS基因的表达，而TNFα主要通过诱导培养的VSMC中的一种中间蛋白来诱导它。
