首页> 外文期刊>Cellular immunology >Thalidomide inhibits interferon-gamma-mediated nitric oxide production in mouse vascular endothelial cells.
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Thalidomide inhibits interferon-gamma-mediated nitric oxide production in mouse vascular endothelial cells.

机译:沙利度胺抑制小鼠血管内皮细胞中干扰素-γ介导的一氧化氮的产生。

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摘要

Thalidomide is known as an anti-angiogenic, anti-tumor, and anti-proliferative agent, widely used in the treatment of some immunological disorders and cancers. The effect of thalidomide on interferon (IFN)-gamma induced nitric oxide (NO) production in mouse vascular endothelial cells was examined in order to elucidate the anti-angiogenic or anti-inflammatory action. Thalidomide inhibited IFN-gamma-induced NO production in mouse END-D cells via reduced expression of an inducible type of NO synthase (iNOS) protein and mRNA. Since thalidomide did not alter the cell surface expression of IFN-gamma receptor, the NO inhibition was suggested to be due to the impairment of IFN-gamma-induced intracellular event by thalidomide. Thalidomide inhibited the phosphorylation of IRF1, which was required for the iNOS expression. Moreover, it inhibited the phosphorylation of STAT1, an upstream molecule of IRF1, in IFN-gamma signaling. Thalidomide did not inhibit the JAK activation in response to IFN-gamma. A phosphatase inhibitor, sodium orthovanadate, abolished the inhibitory action of thalidomide. Therefore, thalidomide was suggested to inhibit IFN-gamma-induced NO production via impaired STAT1 phosphorylation.
机译:沙利度胺被称为抗血管生成,抗肿瘤和抗增殖剂,广泛用于治疗某些免疫性疾病和癌症。为了阐明抗血管生成或抗炎作用,研究了沙利度胺对干扰素(IFN)-γ诱导的小鼠血管内皮细胞中一氧化氮(NO)生成的影响。沙利度胺通过减少诱导型NO合酶(iNOS)蛋白和mRNA的表达来抑制IFN-γ诱导的小鼠END-D细胞中NO的产生。由于沙利度胺不会改变IFN-γ受体的细胞表面表达,因此提示NO抑制是由于沙利度胺对IFN-γ诱导的细胞内事件的损害。沙利度胺抑制iNOS表达所需的IRF1磷酸化。此外,它抑制了IFN-γ信号转导中IRF1的上游分子STAT1的磷酸化。沙利度胺不抑制响应于IFN-γ的JAK活化。磷酸酶抑制剂原钒酸钠取消了沙利度胺的抑制作用。因此,沙利度胺被建议通过STAT1磷酸化受损来抑制IFN-γ诱导的NO产生。

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