Expression of cyclooxygenase-2 in rat vascular smooth muscle cells is unrelated to nuclear factor-κB activation

Abstract

The promoter region of cyclooxygenase-2 (COX-2) gene contains binding sites for a number of important transcription factors including cyclic AMP response element, nuclear factor-IL6, nuclear factor-κB (NF-κB) and TGF-β response element. Several reports have documented that the activation of NF-κB triggers the expression of COX-2 gene. In the present study, NF-κB was activated by TNF-α in rat aortic smooth muscle cells as demonstrated by electrophoretic mobility shift assay. The activity of NF-κB induced by TNF-α was blocked by calpain inhibitor I, a potent NF-κB inhibitor. However, the activation of NF-κB was not related to the expression of COX-2 induced by TNF-α since calpain inhibitor I blocked the activation of NF-κB but not the expression of COX-2 mRNA or protein. Mutation of rat COX-2 NF-κB-like sites in the promoter region did not significantly reduce the promoter activity. These results suggest that the transcriptional regulation of COX-2 expression by NF-κB depends upon the types of cells studied and that activation of this transcription factor alone does not play an important role in the expression of COX-2 in rat smooth muscle cells.