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 mRNA 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 the 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.