Regulatory feedback loop between NF-κB and MCP-1-induced protein 1 RNase
Regulatory feedback loop between NF-κB and MCP-1-induced protein 1 RNase
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DOI：
10.1111/j.1742-4658.2009.07273.x
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发表时间：
2009-10-01
期刊：
影响因子：
5.4
通讯作者：
Jura, Jolanta
中科院分区：
文献类型：
--
作者：
Skalniak, Lukasz;Mizgalska, Danuta;Jura, Jolanta
最近在单核细胞趋化蛋白1(MCP-1)处理的人外周血单核细胞和IL-1β刺激的人单核细胞来源的巨噬细胞中发现了编码MCP-1诱导蛋白1(MCPIP)的新基因ZC3H12A。这些实验表明，在促炎症分子如MCP-1、IL-1β、肿瘤坏死因子a和脂多糖的刺激下，该基因经历了快速而有效的转录诱导。在这里，我们证明了IL-1β对ZC3H12A的诱导主要是依赖于NF-kappa B的，因为抑制这一信号通路会导致ZC3H12A转录激活的损害。我们的结果表明，在ZC3H12A基因的第二内含子中存在一个IL-1β反应区，它包含四个功能性的NF-kappa B结合位点。因此，我们认为该转录增强子在IL-1β刺激后转导ZC3H12A转录诱导信号。最近的报道表明，MCPIP是In的负性调节因子。炎症过程，因为它参与了编码某些促炎细胞因子的转录本的降解。我们的观察为核因子-kappa B激活中的一个新的负反馈回路提供了证据，并指出了MCPIP在治疗各种病理状态中的潜在意义，例如涉及核因子-kappa B系统功能紊乱的糖尿病或癌症。
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.