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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1752.)
© 2007 American Heart Association, Inc.

Vascular Biology

Interferon- Suppresses Cyclooxygenase-2 Promoter Activity by Inhibiting C-Jun and C/EBPß Binding

Wu-Guo Deng; Alberto J. Montero; Kenneth K. Wu

From the University of Texas Health Science Center (W.-G.D., A.J.M., K.K.W.) and M.D. Anderson Cancer Center (W.-G.D., A.J.M., K.K.W.), Houston, Tex; and the National Health Research Institutes (K.K.W.), Zhunan, Miaoli, Taiwan. Present address for A.J.M.: Department of Internal Medicine, Medical University of South Carolina, Charleston.

Correspondence to Kenneth K. Wu, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan. E-mail kkgo{at}nhri.org.tw; or University of Texas Health Science Center, 6431 Fannin, MSB 5.016, Houston, TX 77030-1503. E-mail Kenneth.K.Wu@uth.tmc.edu

Objective— Cyclooxygenase-2 (COX-2) and interferon (IFN) are overexpressed in vascular inflammatory and atherosclerotic lesions. We postulated that IFN suppresses COX-2 expression at the transcriptional level.

Methods and Results— The effect of IFN on COX-2 expression was evaluated in several types of human cells stimulated with phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-1ß, or tumor necrosis factor (TNF) . IFN 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 ß (C/EBPß), or NF-B to their respective regulatory elements on COX-2 promoter. IFN blocked C-Jun and C/EBPß but not C-Fos or p50 NF-B binding as determined by in vitro binding assays and chromatin immunoprecipitation assay. p300 binding to COX-2 promoter was inhibited by IFN in a manner comparable to C-Jun and C/EBPß binding.

Conclusions— IFN suppresses proinflammatory mediator-induced COX-2 transcription by selective inhibition of C-Jun and C/EBPß DNA binding activity and p300 recruitment in human cells. Because IFN is coexpressed with COX-2 in vascular lesions, it may play a role in controlling COX-2–mediated inflammatory changes.

INF- suppressed proinflammatory mediator-induced transcriptional activation in human cells by selective inhibition of C-Jun and C/EBPß binding to their respective response elements on COX-2 promoter. We propose that IFN may represent an important factor for controlling COX-2–mediated vascular inflammatory diseases including the development of atheromatous plaque.

Key Words: interferon • cyclooxygenase-2 • atherosclerosis • plaque instability • inflammation