Cyclooxygenase-2 Induced by Zymosan in Human Monocyte-Derived Dendritic Cells Shows High Stability, and Its Expression Is Enhanced by Atorvastatin

Abstract

Cyclooxygenase (COX)-2 is a central enzyme of arachidonic acid metabolism, and its modulation by statins may explain some of the myocardial protective effects of these drugs. Dendritic cells (DCs) play a central role in microbial defense and in atherogenesis, and COX-2 expression in DCs is important for their migration to lymph nodes and antibody response, thus explaining why prostaglandin E(2) is a main component of the cocktails used to prepare DCs for clinical applications. On this basis, we addressed the effect of atorvastatin (ATV) on the release of arachidonic acid and on the expression of COX-2 in human monocyte-derived DCs. Although ATV on its own lacked any effect on COX-2 protein induction expression, it enhanced the release of arachidonic acid, the expression of COX-2 protein, and the production of prostaglandin E(2) induced by the fungal wall extract zymosan, and to a lower extent the effect of peptidoglycan. The effect on COX-2 protein was observed mainly 24 h after stimulation by zymosan and was not reverted by mevalonate, thus pointing to an effect unrelated to cholesterol metabolism. It is noteworthy that COX-2 protein showed a great stability, with a t((1/2)) of approximately 12 h, which was enhanced in the presence of ATV. In view of the important role played by COX-2 on DC function, these data indicate that ATV, by enhancing COX-2 stability, may increase DC function after infectious bouts and also counteract some of the risks associated with sustained inhibition of COX-2.