p38-dependent activation of interferon regulatory factor 3 by lipopolysaccharide.
Interferon regulatory factor 3 (IRF3) is known to participate in the transcriptional induction of interferon (IFN) alpha and IFNbeta genes, as well as of a number of interferon-stimulated genes (ISGs), as a result of viral infection. In the present study we demonstrate the activation of IRF3 followed by ISG induction after exposure of cells to the bacterial cell wall component lipopolysaccharide. Engagement of Toll-like receptors by lipopolysaccharide triggered the nuclear translocation of IRF3, followed by its DNA binding and the subsequent induction of several interferon-regulated genes. Transcriptional activation of ISGs occurred in a protein synthesis independent manner, but was sensitive to inhibition of the stress-activated protein kinase, p38. The activation of IRF3 by viral particles or bacterial membrane components suggests that this signaling pathway might contribute to the evolutionary conserved innate immune response.
Navarro
L
L
Department of Biology, University of California San Diego Cancer Center, University of California, La Jolla, California 92093-0322, USA.
David
M
M
D001254:Astrocytoma; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; C494232:IRF3 protein, human; D007093:Imidazoles; D050838:Interferon Regulatory Factor-3; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D011725:Pyridines; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one