Interferon-γ Suppresses Cyclooxygenase-2 Promoter Activity by Inhibiting C-Jun and C/EBPβ Binding
- 1 August 2007
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 27 (8), 1752-1759
- https://doi.org/10.1161/atvbaha.107.144352
Abstract
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.Keywords
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