論文 - 詳細
RRC ID | 36852 |
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著者 | Hiroi M, Sakaeda Y, Yamaguchi H, Ohmori Y. |
タイトル | Anti-inflammatory cytokine interleukin-4 inhibits inducible nitric oxide synthase gene expression in the mouse macrophage cell line RAW264.7 through the repression of octamer-dependent transcription. |
ジャーナル | Mediators Inflamm |
Abstract |
Inducible nitric oxide synthase (iNOS) is a signature molecule involved in the classical activation of M1 macrophages and is induced by the Nos2 gene upon stimulation with Th1-cell derived interferon-gamma (IFNγ) and bacterial lipopolysaccharide (LPS). Although the anti-inflammatory cytokine IL-4 is known to inhibit Nos2 gene expression, the molecular mechanism involved in the negative regulation of Nos2 by IL-4 remains to be fully elucidated. In the present study, we investigated the mechanism of IL-4-mediated Nos2 transcriptional repression in the mouse macrophage-like cell line RAW264.7. Signal transducer and activator of transcription 6 (Stat6) knockdown by siRNA abolished the IL-4-mediated inhibition of Nos2 induced by IFNγ/LPS. Transient transfection of a luciferase reporter gene containing the 5'-flanking region of the Nos2 gene demonstrated that an octamer transcription factor (OCT) binding site in the promoter region is required for both positive regulation by IFNγ/LPS and negative regulation by IL-4. Although IL-4 had no inhibitory effect on the DNA-binding activity of constitutively expressed Oct-1, IL-4-induced Nos2-reporter transcriptional repression was partially attenuated by overexpression of the coactivator CREB-binding protein (CBP). These results suggest that a coactivator/cofactor that functionally interacts with Oct-1 is a molecular target for the IL-4-mediated inhibition of Nos2 and that IL-4-activated Stat6 represses Oct-1-dependent transcription by competing with this coactivator/cofactor. |
巻・号 | 2013 |
ページ | 369693 |
公開日 | 2013-1-1 |
DOI | 10.1155/2013/369693 |
PMID | 24459328 |
PMC | PMC3891534 |
MeSH | Animals Cells, Cultured Interferon-gamma / pharmacology Interleukin-4 / pharmacology* Lipopolysaccharides / pharmacology Macrophages / enzymology Membrane Proteins / physiology Mice Nitric Oxide Synthase Type II / antagonists & inhibitors Nitric Oxide Synthase Type II / genetics* Octamer Transcription Factor-1 / physiology* Organic Cation Transport Proteins Organic Cation Transporter 2 Phosphoproteins / physiology Promoter Regions, Genetic STAT6 Transcription Factor / physiology |
IF | 3.758 |
引用数 | 15 |
リソース情報 | |
ヒト・動物細胞 | BCL1-B20(RCB2618) |