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

J Immunol. 2008 Jun 15;180(12):8011-9. doi: 10.4049/jimmunol.180.12.8011.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication / genetics
  • Autocrine Communication / immunology
  • Cell Line
  • Cells, Cultured
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / antagonists & inhibitors
  • DEAD-box RNA Helicases / deficiency
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / physiology*
  • Genetic Vectors
  • Humans
  • Inflammation Mediators / administration & dosage
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / pharmacology
  • Interferon-beta / metabolism
  • Lipopolysaccharides / administration & dosage*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Knockout
  • Salmonella Infections, Animal / immunology
  • Salmonella Infections, Animal / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Time Factors
  • Toll-Like Receptor 4 / physiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Inflammation Mediators
  • Lipopolysaccharides
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Interferon-beta
  • Ddx58 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases