Glucocorticoid-mediated suppression of the promoter activity of the cyclooxygenase-2 gene is modulated by expression of its receptor in vascular endothelial cells

Cyclooxygenase-2 (COX-2), an inducible isozyme of cyclooxygenase, is expres sed selectively in response to various inflammatory stimuli such as lipopol ysaccharide (LPS) and its expression is suppressed by the glucocorticoid de xamethasone (DEX) in numerous types of cells. However, LPS-enhanced product ion of prostacyclin in bovine arterial endothelial cells (BAEC) was not sig nificantly decreased by treatment with DEX but was suppressed by selective COX-2 inhibitors. This is consistent with the finding that DEX was not effe ctive at preventing the expression of LPS-induced COX-2 mRNA. Transient tra nsfection analysis showed that DEX did not suppress the LPS-induced promote r activity of the 5'-flanking region of the human COX-2 gene (nucleotides - 327 to +59), Since RNA blot analysis indicated low-level expression of gluc ocorticoid receptor (GR) mRNA in BAEC, a GR-expression vector was transfect ed to evaluate the role of the GR in the COX-2 promoter activity. It was fo und that DEX mediated the suppression of the LPS-induced COX-2 promoter act ivity in a dose-dependent manner. These results suggest that the HEX-mediat ed suppression of LPS-induced promoter activity of the COX-2 gene is modula ted by expression of the GR, which will be possible to account for a unique expression pattern of the COX-2 gene in BAEC. (C) 1999 Academic Press.