| First Author | Sakaguchi S | Year | 2003 |
| Journal | Biochem Biophys Res Commun | Volume | 306 |
| Issue | 4 | Pages | 860-6 |
| PubMed ID | 12821121 | Mgi Jnum | J:276595 |
| Mgi Id | MGI:6314329 | Doi | 10.1016/s0006-291x(03)01049-0 |
| Citation | Sakaguchi S, et al. (2003) Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock. Biochem Biophys Res Commun 306(4):860-6 |
| abstractText | 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. |
