論文 - 詳細
| RRC ID | 11870 |
|---|---|
| 著者 | Johnson J, Molle C, Aksoy E, Goldman M, Goriely S, Willems F. |
| タイトル | A conventional protein kinase C inhibitor targeting IRF-3-dependent genes differentially regulates IL-12 family members. |
| ジャーナル | Mol Immunol |
| Abstract |
Protein kinase C (PKC) isoforms play a critical role in the regulation of innate immune responses. We have previously demonstrated that conventional PKC (cPKC) α is involved in interferon regulatory factor 3 (IRF-3) activation and IFN-β synthesis. Herein, we investigated the role of cPKCs in the regulation of IL-12 family members expression mediated by the Toll-like receptor 3 (TLR3) and TLR4. First, inhibition of cPKCs activity in human DCs by a cPKC-specific inhibitor, Gö6976 downregulated the expression of IL-12p70 and IL-27p28 but not IL-12/IL-23p40, IL-23, IL-27EBI3 induced by LPS or poly(I:C). Furthermore, reporter gene assays in RAW 264.7 macrophages showed that cPKCs regulate IL-12p35 and IL-27p28 promoter activities since Gö6976 repressed LPS and poly(I:C)-mediated transcriptional activities of IL-12p35 and IL-27p28. In contrast, no effect was observed with IL-12/IL-23p40 and IL-23p19 reporter constructs. These results prompted us to study the role of IRF-3 on IL-23 expression. Bone marrow-derived DC (BMDCs) from IRF-3(-/-) mice produced comparable levels of IL-23 induced by both LPS and poly(I:C) as compared to wild type BMDCs, indicating that IRF-3 is not involved in IL-23 production. Finally, BMDCs from PKCα(-/-) mice displayed a reduced synthesis of IL-27 induced by poly(I:C). Collectively, these data identify cPKCs as critical components that control IRF-3-dependent IL-12p35 and IL-27p28 gene expression downstream of TLR3 and TLR4. |
| 巻・号 | 48(12-13) |
| ページ | 1484-93 |
| 公開日 | 2011-7-1 |
| DOI | 10.1016/j.molimm.2011.04.006 |
| PII | S0161-5890(11)00130-1 |
| PMID | 21550664 |
| MeSH | Animals Carbazoles / pharmacology Dendritic Cells / drug effects Dendritic Cells / immunology Dendritic Cells / metabolism Gene Expression Regulation Interferon Regulatory Factor-3 / metabolism* Interleukin-12 / biosynthesis Interleukin-12 / genetics* Interleukin-12 / metabolism Interleukin-17 / biosynthesis Interleukin-17 / genetics Interleukin-23 / biosynthesis Interleukin-23 / genetics Interleukins / genetics Interleukins / metabolism Lipopolysaccharides / immunology Mice Mice, Transgenic Poly I-C / immunology Polymerase Chain Reaction Protein Kinase C / antagonists & inhibitors* Protein Kinase C / metabolism* Toll-Like Receptor 3 / metabolism Toll-Like Receptor 4 / metabolism Transcription, Genetic / drug effects |
| IF | 3.641 |
| 引用数 | 7 |
| WOS 分野 | IMMUNOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC00858 |