Essential role of IRF-3 in lipopolysaccharide-induced interferon-β gene expression and endotoxin shock
| Autor: | Hideo Negishi, Chigusa Nakajima, Akinori Takaoka, Tadatsugu Taniguchi, Masataka Asagiri, Tatsuaki Mizutani, Kenya Honda, Shinya Sakaguchi |
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| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Transcriptional Activation Chemokine Time Factors Lipopolysaccharide Interferon Regulatory Factor-7 medicine.medical_treatment Biophysics Biochemistry Mice chemistry.chemical_compound Immune system Gene expression medicine Animals RNA Messenger Cycloheximide Luciferases Receptor Molecular Biology Transcription factor Genes Dominant Protein Synthesis Inhibitors Dose-Response Relationship Drug biology Reverse Transcriptase Polymerase Chain Reaction Dendritic Cells Interferon-beta Cell Biology Molecular biology Up-Regulation DNA-Binding Proteins Endotoxins Cytokine Gene Expression Regulation chemistry TLR4 biology.protein Cytokines Interferon Regulatory Factor-3 lipids (amino acids peptides and proteins) Signal Transduction Transcription Factors |
| Zdroj: | Biochemical and Biophysical Research Communications. 306:860-866 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/s0006-291x(03)01049-0 |
| Popis: | Type I interferons (IFN-α/β) 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 - β 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 - β 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 - β , 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. |
| Databáze: | OpenAIRE |
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