N-Oleoylethanolamine reduces inflammatory cytokines and adhesion molecules in TNF-α-induced human umbilical vein endothelial cells by activating CB2 and PPAR-α.

Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Peroxisome proliferator-activated receptor-alpha (PPAR-α) and cannabinoid receptor 2 (CB2) crucially impact the modulation of inflammation. N-Oleoylethanolamine (OEA), a natural agonist of PPAR-α, can also upregulate the expression of CB2 in human umbilical vein endothelial cells (HUVECs) and further shows an anti- atherosclerotic effect. Our study was designed to determinate whether OEA could inhibit inflammation in HUVECs induced by tumour necrosis factor-α (TNF-α) and to identify the mechanism of OEA function. IL-6, IL-8, VCAM-1 and ICAM-1 levels were detected in HUVECs exposed to TNF-α in the presence of OEA. The results showed that OEA suppressed the expression of IL-6, IL-8, VCAM-1 and ICAM-1 in a dose-dependent manner. OEA also enhanced CB2 and PPAR-α receptor expression, which contributed to its anti- inflammatory effect. OEA inhibited the nuclear factor-κB (NF-κB) pathway, and the effect of OEA on NF-κB was partly abolished when HUVECs were pre-treated with either CB2 or PPAR-α antagonist. OEA attenuated TNF-α-induced inflammation in HUVECs by upregulating the expression of CB2 and PPAR-α receptors. Furthermore, OEA suppresses the NF-κB pathway. These results suggest that OEA exerts anti-inflammatory and anti-adhesive effects on HUVECs.