Wang Jing, Wu Su, Jin Xin, Li Mingtao, Chen Shiyong, Teeling Jessica L, Perry V Hugh, Gu Jun
National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, China.
J Immunol. 2008 Jun 15;180(12):8011-9. doi: 10.4049/jimmunol.180.12.8011.
LPS is the known component of bacterial pathogens that stimulates a number of proinflammatory factors. However, the mechanism of the induction of these factors by LPS has not been fully elucidated. We show here that LPS induces retinoic acid-inducible gene-I (RIG-I) in vitro and in vivo as a result from autocrine secretion of IFN-beta in macrophages. TIR-domain-containing adapter-inducing IFN-beta-deficient mouse embryo fibroblast (trif(-/)(-)) fail to show expression of RIG-I following LPS stimulation. Interference of RIG-I expression short interfering RNA represses the expression of LPS-induced TNF-alpha, whereas over-expression of RIG-I leads to the activation of TNF-alpha promoter and the induction of TNF-alpha expression. LPS- and IFN-beta-induced TNF-alpha are suppressed in RIG-I-deficient mouse embryo fibroblasts (rig(-/)(-)). Thus, RIG-I plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-alpha.
脂多糖（LPS）是细菌病原体的已知成分，可刺激多种促炎因子。然而，LPS诱导这些因子的机制尚未完全阐明。我们在此表明，LPS在体外和体内均可诱导视黄酸诱导基因I（RIG-I），这是巨噬细胞中IFN-β自分泌的结果。含TIR结构域的接头诱导IFN-β缺陷型小鼠胚胎成纤维细胞（trif(-/-)）在LPS刺激后未能显示RIG-I的表达。干扰RIG-I表达的小干扰RNA可抑制LPS诱导的TNF-α表达，而RIG-I的过表达则导致TNF-α启动子的激活和TNF-α表达的诱导。在RIG-I缺陷型小鼠胚胎成纤维细胞（rig(-/-)）中，LPS和IFN-β诱导的TNF-α受到抑制。因此，RIG-I在巨噬细胞响应LPS刺激时TNF-α的表达中起关键作用，主要是在LPS诱导的TNF-α晚期表达中。
