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)-1, 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 (C/EBP), or NF-B to their respective regulatory elements on COX-2 promoter. IFN blocked C-Jun and C/EBP 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/EBP binding.

Conclusions--IFN suppresses proinflammatory mediator-induced COX-2 transcription by selective inhibition of C-Jun and C/EBP 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.