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Biochem Biophys Res Commun. 2003 Jul 11;306(4):860-6.

Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock.

Author information

1
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract

Type I interferons (IFN-alpha/beta) affect many aspects of immune responses. Many pathogen-associated molecules, including bacterial lipopolysaccharide (LPS) and virus-associated double-stranded RNA, induce IFN gene expression through activation of distinct Toll-like receptors (TLRs). Although much has been studied about the activation of the transcription factor IRF-3 and induction of IFN-beta gene by the LPS-mediated TLR4 signaling, definitive evidence is missing about the actual role of IRF-3 in LPS responses in vitro and in vivo. Using IRF-3 deficient mice, we show here that IRF-3 is indeed essential for the LPS-mediated IFN-beta gene induction. Loss of IRF-3 also affects the expression of profile of other cytokine/chemokine genes. We also provide evidence that the LPS/TLR4 signaling activates IRF-7 to induce IFN-beta, if IRF-7 is induced by IFNs prior to LPS simulation. Finally, the IRF-3-deficient mice show resistance to LPS-induced endotoxin shock. These results place IRF-3 as a molecule central to LPS/TLR4 signaling.

PMID:
12821121
DOI:
10.1016/s0006-291x(03)01049-0
[Indexed for MEDLINE]

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