TAILIEUCHUNG - Báo cáo khoa học: The interferon-stimulated gene factor 3 complex mediates the inhibitory effect of interferon-b on matrix metalloproteinase-9 expression

Matrix metalloproteinase-9 (MMP-9) displays a preference for a broad range of substrates including extracellular matrix proteins and cytokines. MMP-9 plays an important role in physiological processes, as well as in inflammatory diseases and numerous cancers. | ễFEBS Journal The interferon-stimulated gene factor 3 complex mediates the inhibitory effect of interferon-b on matrix metalloproteinase-9 expression Xueyan Zhao Susan Nozell Zhendong Ma and Etty N. Benveniste Department of Cell Biology University of Alabama at Birmingham AL USA Keywords gene regulation interferon MMP transcription factors signal transduction Correspondence E. N. Benveniste Department of Cell Biology MCLM 395 University of Alabama at Birmingham 1530 Third Avenue South Birmingham AL 35294-0005 USA Fax 1 205 975 6748 Tel 1 205 934 7667 E-mail tika@ Received 8 September 2007 revised 19 October 2007 accepted 24 October 2007 doi Matrix metalloproteinase-9 MMP-9 displays a preference for a broad range of substrates including extracellular matrix proteins and cytokines. MMP-9 plays an important role in physiological processes as well as in inflammatory diseases and numerous cancers. Interferon-b is a pleiotropic cytokine with antiviral antiproliferative and immunomodulatory activities. Interferon-b positively regulates gene expression predominantly through the Janus kinase-signal transducer and activator of transcription STAT pathway. However little is known about the mechanisms used by inter-feron-b to negatively regulate gene expression. In the present study we show that interferon-b inhibits MMP-9 gene expression at the transcriptional level. Using cell lines deficient in three components of the interferon-b-activated interferon-stimulated gene factor 3 ISGF3 complex . STAT-1 STAT-2 and interferon regulatory factor 9 the results of our study indicate that all three members are required for interferon-b inhibition. Chromatin immunoprecipitation assays demonstrate that interferon-b reduces recruitment of transcriptional activators and coactivators such as nuclear factor kappa B p65 Sp1 CREB-binding protein and p300 to the MMP-9 promoter and decreases the degree of histone acetylation at the MMP-9 promoter. This

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