Regulation of the expression of cyclooxygenases and production of prostaglandin i2 and e2 in human coronary artery endothelial cells by curcumin

Curcumin regulates prostaglandin (PG) synthesis in a variety of cells. PGE2 and PGI2 are generated from arachidonic acid (AA) by cyclooxygenases 1 and 2 (COX-1 and COX-2) and the synthase (PGES and PGI2S) pathways. This study evaluates the in vitro effect of curcumin on the expression of COX-1, COX-2, PGI2S and microsomal PGES-1 (mPGES-1), and the production of PGE2 and PGI2 in human coronary artery endothelial cells (HCAEC). HCAEC monolayers were incubated with curcumin and the expression of mRNA, protein and the production of PGI2 and PGE2 were quantified. Incubation of HCAEC with curcumin led to a time and concentration-dependent increases in COX-2 mRNA with a small but significant decrease in COX-1 expression. Curcumin also stimulated the expression of PGI2S and mPGES-1 mRNA. Although curcumin stimulated COX-2, PGI2S and mPGES-1 gene expression, it failed to increase PGI2 or PGE2 production. Interestingly, supplementation of the culture medium with AA increased prostanoid production by both quiescent and curcumin-treated cells. However, in comparison to the quiescent cells, the prostanoid production by curcumin-treated cells was markedly enhanced as AA concentrations in the medium were increased, and the enhanced prostanoid production was blocked by presence of COX-2 specific inhibitor. Taken together, these results suggest that curcumin regulates prostanoid homeostasis in HCAEC by modulating multiple steps including the expression of COX-1, COX-2, PGI2S and mPGES-1.