Oxidized-HDL3 modulates the expression of Cox-2 in human endothelial cells

Modified high density lipoprotein (HDL) has been suggested to modulate endothelial expression of proinflammatory genes. Since oxidised HDL (Ox-HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the effect of Ox-HDL₃ on the expression of Cox-1 or Cox-2. Ox-HDL₃, increased Cox-2 mRNA and protein expression in endothelial cells while no effect on Cox-1 expression was observed. The intracellular pathways involved in this effect were investigated. The incubation with specific inhibitors of intracellular kinases showed that PI3K is mainly involved in the Ox-HDL₃-dependent Cox-2 induction. Transient transfection experiments suggested that the NF-IL6 response element in the proximal promoter (-327 to 59) is involved in Ox-HDL₃-mediated Cox-2 expression. These data suggest that Ox-HDL induce Cox-2 expression in endothelial cells through a PI3K/NF-IL6-dependent pathway.