Retinoic Acid-Inducible Gene-I Mediates Late Phase Induction of TNF-α by Lipopolysaccharide

Abstract

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-β in macrophages. TIR-domain-containing adapter-inducing IFN-β-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-α, whereas over-expression of RIG-I leads to the activation of TNF-α promoter and the induction of TNF-α expression. LPS- and IFN-β-induced TNF-α are suppressed in RIG-I-deficient mouse embryo fibroblasts (rig−/−). Thus, RIG-I plays a key role in the expression of TNF-α in macrophages in response to LPS stimulation, mainly for the late phase LPS-induced expression of TNF-α.