TAILIEUCHUNG - Báo cáo khoa học: Regulatory feedback loop between NF-jB and MCP-1-induced protein 1 RNase

A novel geneZC3H12A, 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)-1b. These experiments revealed that the gene undergoes rapid and potent transcription induction upon stimulation with proinflammatory molecules, such as MCP-1, IL-1b, tumour necrosis factor aand lipopolysaccharide. | ễFEBS Journal Regulatory feedback loop between NF-kB and MCP-1-induced protein 1 RNase Lukasz Skalniak Danuta Mizgalska Adrian Zarebski Paulina Wyrzykowska Aleksander Koj and Jolanta Jura Department of CellBiochemistry Faculty of Biochemistry Biophysics and Biotechnology Jagiellonian University Krakow Poland Keywords inflammation MCPIP NF-kappa B transcription start site transcriptional regulation Correspondence J. Jura Department of CellBiochemistry Faculty of Biochemistry Biophysics and Biotechnology 7 Gronostajowa St 30-387 Krakow Poland Fax 48 12 664 6902 Tel 48 12 664 6359 E-mail Website http Received 23 June 2009 revised 6 August 2009 accepted 10 August 2009 doi 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 -1p. These experiments revealed that the gene undergoes rapid and potent transcription induction upon stimulation with proinflammatory molecules such as MCP-1 IL-1b tumour necrosis factor a and lipopolysaccharide. Here we show that the induction of ZC3H12A by IL-1b is predominantly NF-KB-dependent because inhibition of this signalling pathway results in the impairment of ZC3H12A transcription activation. Our results indicate the presence of an IL-1 b-responding region within the second intron of the ZC3H12A gene which contains four functional NF-KB-binding sites. Therefore we propose that this transcription enhancer transduces a ZC3H12A transcriptioninducing signal after IL-1b stimulation. Recent reports suggest that MCPIP acts as a negative regulator of inflammatory 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-KB and point to .

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• A novel geneZC3H12A
• 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) 1b
• These experiments revealed that the gene undergoes rapid and potent transcription induction upon stimulation with proinflammatory molecules
• such as MCP 1
• IL 1b
• tumour necrosis factor aand lipopolysaccharide
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