Acyl chain-dependent effect of lysophosphatidylcholine on cyclooxygenase (COX)-2 expression in endothelial cells

Abstract

ObjectivePreviously we identified palmitoyl-, oleoyl- linoleoyl-, and arachidonoyl-lysophosph-atidylcholine (LPC 16:0, 18:1, 18:2 and 20:4) as the most prominent LPC species generated by endothelial lipase (EL). In the present study, we examined the capacity of those LPC to modulate expression of cyclooxygenase (COX)-2 in vascular endothelial cells. Methods & resultsLPC 16:0 and 20:4 promoted both COX-2 mRNA- and protein synthesis with different potencies and kinetics. While LPC 18:1 induced a weak and transient increase in COX-2 mRNA, but not protein, LPC 18:2 increased COX-2 protein, without impacting mRNA. Chelation of intracellular Ca2+ and inhibition of p38 MAPK markedly attenuated 16:0 LPC- and 20:4 LPC- elicited induction of COX-2 expression, whereas inhibition of phospholipase C (PLC) attenuated only the effect of 16:0 LPC. LPC 16:0 and 20:4 differed markedly in their potencies to increase cytosolic Ca2+ concentration and in the kinetics of p38 MAPK activation. While the effects of 16:0 and 20:4 LPC on COX-2 expression were profoundly sensitive to silencing of either c-Jun or p65 (NF-κB), respectively, silencing of cyclic AMP responsive element binding protein (CREB) attenuated markedly the effect of both LPC. ConclusionOur results indicate that the tested LPC species are capable of inducing COX-2 expression, whereby the efficacy and the relative contribution of underlying signaling mechanisms markedly differ, due to the length and degree of saturation of LPC acyl chains.