Curcumin stimulates cyclooxygenase-2 (COX-2), prostaglandin I2 synthase (PGI2S) and PGE2 synthase (PGE2S) gene expression in human coronary artery endothelial cells (93.19)

Abstract

Abstract Curcumin is reported to decrease atherosclerosis progression in Apo-E/LDL receptor knockout mice. PGI2 and PGE2 are generated from arachidonic acid (AA) by the COX-PGI2S/PGE2S pathway and are known to have important roles in cardiovascular function. In this study, we evaluated the in vitro effect of curcumin on the expression and function of COX-2, PGI2S and PGE2S in human coronary artery endothelial cells (HCAEC). HCAEC monolayers were incubated with curcumin (1.25-10 μM), and the mRNA and protein expressions were monitored by qRT-PCR and Western blots, respectively. PGI2 and PGE2 levels in the culture supernatants were quantified by EIA. Incubation of HCAEC with curcumin led to concentration-dependent increases in COX-2 mRNA and protein expression without change in COX-1 expression. Curcumin also induced 2-fold increases in PGI2S and PGE2S gene expression. Despite the increase in COX-2, PGI2S and PGE2S gene expression, curcumin failed to increase PGI2 or PGE2 production. Furthermore, curcumin inhibited LPS-induced PGE2 and PGI2 production by HCAEC and exogenous AA could not reverse the inhibitory effect. These results show that curcumin acts both as an inducer of COX-2, PGI2S and PGE2S gene expression and as an inhibitor of stimulated PGE2 and PGI2 synthesis. The ability of curcumin to regulate prostanoid biosynthesis in HCAEC indicates its therapeutic potential for cardiovascular disease. (Supported by NIH R01-HL070101 and the Carey Arthritis Fund).