| RRC ID |
1855
|
| 著者 |
Goriely S, Molle C, Nguyen M, Albarani V, Haddou NO, Lin R, De Wit D, Flamand V, Willems F, Goldman M.
|
| タイトル |
Interferon regulatory factor 3 is involved in Toll-like receptor 4 (TLR4)- and TLR3-induced IL-12p35 gene activation.
|
| ジャーナル |
Blood
|
| Abstract |
Interleukin-12 (IL-12) is a heterodimeric cytokine produced by dendritic cells (DCs) in response to Toll-like receptor (TLR) ligation. While the mechanisms regulating IL-12p40 chain gene expression are well characterized, molecular events involved in IL-12p35 chain gene activation remain to be clarified. Since IL-12p35 mRNA was induced in human DCs activated through TLR3 or TLR4 but not TLR2, we investigated the potential role of interferon regulatory factor 3 (IRF-3) in IL-12p35 gene transactivation. First, a binding site for IRF-3 named interferon-stimulated response element-1 (ISRE-1) was identified in the human IL-12p35 promoter region between nucleotides -251 and -240. The ISRE-1 site was required for IL-12p35 gene activation in RAW 264.7 cells stimulated by lipopolysaccharide (LPS) or PolyI:C. Ectopic expression of IRF-3 was found to up-regulate IL-12p35 gene activation in the same system. Furthermore, chromatin immunoprecipitation (ChIP) studies demonstrated that IRF-3 is recruited to ISRE-1 site in TLR4- or TLR3-stimulated human DCs. Finally, experiments on DCs from IRF-3-deficient mice established that TLR4-induced IL-12p35 mRNA and IL-12p70 synthesis are impaired in absence of IRF-3. We conclude that IRF-3 binds to a critical cis-acting element in the IL-12p35 gene promoter and thereby represents a key factor for the induction of IL-12p70 synthesis in DCs.
|
| 巻・号 |
107(3)
|
| ページ |
1078-84
|
| 公開日 |
2006-2-1
|
| DOI |
10.1182/blood-2005-06-2416
|
| PII |
S0006-4971(20)68429-4
|
| PMID |
16219795
|
| MeSH |
Animals
Antiviral Agents / pharmacology
Cell Line
Chromatin Immunoprecipitation
Dendritic Cells / cytology
Dendritic Cells / immunology
Humans
Interferon Regulatory Factor-3 / deficiency
Interferon Regulatory Factor-3 / immunology*
Interleukin-12 / genetics
Interleukin-12 / immunology*
Interleukin-12 Subunit p35
Interleukin-12 Subunit p40
Lipopolysaccharides / pharmacology
Mice
Poly I-C / pharmacology
Protein Subunits / genetics
Protein Subunits / immunology*
Response Elements / genetics
Response Elements / immunology
Toll-Like Receptor 3 / immunology*
Toll-Like Receptor 4 / immunology*
Transcription, Genetic / drug effects
Transcription, Genetic / genetics
Transcription, Genetic / immunology
Up-Regulation / drug effects
Up-Regulation / genetics
Up-Regulation / immunology*
|
| IF |
17.794
|
| 引用数 |
82
|
|
WOS 分野
|
HEMATOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00388
RBRC00858 |
