Retinoic acid-inducible gene-I mediates late phase induction of TNF-alpha by lipopolysaccharide.
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.
National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, China.
Jing
J
Wang
Su
S
Wu
Xin
X
Jin
Mingtao
M
Li
Shiyong
S
Chen
Jessica L
JL
Teeling
V Hugh
VH
Perry
Jun
J
Gu
D000818:Animals; D019898:Autocrine Communication / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016899:Interferon-beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases