論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | F1000Research |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00388 RBRC00858 |