國家衛生研究院 NHRI:Item 3990099045/3278
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    题名: Interferon-gamma suppresses cyclooxygenase-2 promoter activity by inhibiting C-Jun and C/EBP beta binding
    作者: Deng, WG;Montero, AJ;Wu, KK
    贡献者: Institute of Cellular and Systems Medicine
    摘要: OBJECTIVE - Cyclooxygenase-2 (COX-2) and interferon γ (IFNγ) are overexpressed in vascular inflammatory and atherosclerotic lesions. We postulated that IFNγ suppresses COX-2 expression at the transcriptional level. METHODS AND RESULTS - The effect of IFNγ on COX-2 expression was evaluated in several types of human cells stimulated with phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-1β, or tumor necrosis factor (TNF) α. IFNγ concentration-dependently inhibited COX-2 proteins and promoter activities induced by PMA or cytokines in human fibroblasts and monocytic and endothelial cells. PMA and cytokines stimulate binding of C-Jun, C-Fos, CCAAT/enhancer binding protein β (C/EBPβ), or NF-κB to their respective regulatory elements on COX-2 promoter. IFNγ blocked C-Jun and C/EBPβ but not C-Fos or p50 NF-κB binding as determined by in vitro binding assays and chromatin immunoprecipitation assay. p300 binding to COX-2 promoter was inhibited by IFNγ in a manner comparable to C-Jun and C/EBPβ binding. CONCLUSIONS - IFNγ suppresses proinflammatory mediator-induced COX-2 transcription by selective inhibition of C-Jun and C/EBPβ DNA binding activity and p300 recruitment in human cells. Because IFNγ is coexpressed with COX-2 in vascular lesions, it may play a role in controlling COX-2-mediated inflammatory changes. ? 2007 American Heart Association, Inc.
    日期: 2007-08
    關聯: Arteriosclerosis, Thrombosis, and Vascular Biology. 2007 Aug;27(8):1752-1759.
    Link to: http://dx.doi.org/10.1161/atvbaha.107.144352
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1079-5642&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000248176200013
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34547622603
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