期刊
FEBS JOURNAL
卷 276, 期 20, 页码 5892-5905出版社
WILEY
DOI: 10.1111/j.1742-4658.2009.07273.x
关键词
inflammation; MCPIP; NF-kappa B; transcription start site; transcriptional regulation
资金
- European Community's [FP6:MTKD-CT-2006-042586, LSHM-CT-2006-036903]
- Polish Ministry of Scientific Research and Information Technology [63/6PR-UE/2007/7, 339/6PR-UE/2007/7]
A novel gene ZC3H12A, encoding MCP-1-induced protein 1 (MCPIP), was recently identified in human peripheral blood monocytes treated with monocyte chemotactic protein 1 (MCP-1) and in human monocyte-derived macrophages stimulated with interleukin (IL)-1 beta. These experiments revealed that the gene undergoes rapid and potent transcription induction upon stimulation with proinflammatory molecules, such as MCP-1, IL-1 beta, tumour necrosis factor a and lipopolysaccharide. Here we show that the induction of ZC3H12A by IL-1 beta is predominantly NF-kappa B-dependent because inhibition of this signalling pathway results in the impairment of ZC3H12A transcription activation. Our results indicate the presence of an IL-1 beta-responding region within the second intron of the ZC3H12A gene, which contains four functional NF-kappa B-binding sites. Therefore, we propose that this transcription enhancer transduces a ZC3H12A transcription-inducing signal after IL-1 beta stimulation. Recent reports suggest that MCPIP acts as a negative regulator of in. ammatory processes because it is engaged in the degradation of transcripts coding for certain proinflammatory cytokines. Our observations provide evidence for a novel negative feedback loop in the activation of NF-kappa B and point to potential significance of MCPIP in the treatment of various pathological states, such as diabetes or cancer that involve disturbances in the functioning of the NF-kappa B system.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据