Retinoic acid-inducible gene-I mediates late phase induction of TNF-? by lipopolysaccharide

• Main Authors: Wang, Jing (Author), Wu, Su (Author), Jin, Xin (Author), Li, Mingtao (Author), Chen, Shiyong (Author), Teeling, Jessica L. (Author), Perry, V. Hugh (Author), Gu, Jun (Author)
• Format: Article
• Language: English
• Published: 2008-06-15.
• Subjects: Article
• Online Access: Get fulltext

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-? in macrophages. TIR-domain-containing adapter-inducing IFN-?-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-?-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}.