Abstract：
Treatment of cells with interferons (IFNs) induces the phosphorylation of signal transducer and activator of transcription 1 (STAT1), leading to the expression of hundreds of IFN-stimulated genes (ISGs). ISGs exert various antiviral and pro-inflammatory reactions. We have previously reported that ISG56 and ISG54 are induced by polyinosinic-polycytidylic acid (poly IC), an authentic agonist for Toll-like receptor 3 (TLR3), in U373MG human astrocytoma cells. ISG56 and ISG54 are also named as IFN-induced proteins with tetratricopeptide repeats (IFIT) 1 and IFIT2, respectively. In the present study, we demonstrated that poly IC induces the expression of ISG60, also named as IFIT3, in U373MG cells. RNA interference experiments showed that the induction of ISG60 by poly IC was mediated by TLR3, IFN-β, ISG56 and ISG54, whereas ISG60 is involved in poly IC-induced expression of ISG56, ISG54 and a chemokine CXCL10. The level of phosphorylated STAT1 was enhanced by poly IC, and it was inhibited by knockdown of ISG56, ISG54 or ISG60. These results suggest that there is a positive feedback loop between phosphorylated STAT1 and these ISGs.
摘要：
用干扰素（IFN）处理细胞诱导信号转导和转录激活因子1（STAT1）的磷酸化，导致数百个IFN刺激基因（ISG）的表达。ISG发挥各种抗病毒和促炎反应。我们以前报道过，ISG56和ISG54是由聚肌苷酸-聚胞嘧啶酸（聚IC）诱导的，Toll样受体3（TLR3）的真正激动剂，在U373MG人星形细胞瘤细胞中。ISG56和ISG54也分别被命名为具有四三肽重复(IFIT)1和IFIT2的IFN诱导蛋白。在本研究中,我们证明了polyIC在U373MG细胞中诱导ISG60（也称为IFIT3）的表达。RNA干扰实验表明,polyIC对ISG60的诱导是由TLR3、IFN-β、ISG56和ISG54,而ISG60参与聚IC诱导的ISG56、ISG54和趋化因子CXCL10的表达。磷酸化STAT1的水平被polyIC增强，它被ISG56，ISG54或ISG60的敲低抑制。这些结果表明磷酸化STAT1和这些ISG之间存在正反馈回路。
