Sphingosylphosphorylcholine stimulates CCL2 production and ICAM expression from human umbilical vein endothelial cells (60.2)

Abstract

Abstract We investigated the functional role of sphingosylphosphorylcholine (SPC), a component of high density lipoprotein (HDL) particles, in human umbilical vein endothelial cells (HUVECs). SPC stimulation induced production of the CCL2 chemokine in a PTX-sensitive G-protein-dependent manner. SPC treatment caused the activation of NF-κB and AP-1, which are essential for SPC-induced CCL2 production, and also induced the activation of three MAPKs, ERK, p38 MAPK, and JNK. p38 MAPK or JNK by specific inhibitors caused a dramatic decrease in SPC-induced CCL2 production. The Jak/STAT3 pathway was also activated upon SPC stimulation of HUVECs. Pretreatment with a Jak inhibitor blocked not only SPC-induced p38 MAPK and JNK activation but also NF-κB and AP-1 activation. Our results suggest that SPC stimulates HUVECs, resulting in Jak/STAT3-, NF-κB-, and AP-1-mediated CCL2 production. We also observed that SPC stimulated expression of the adhesion molecule ICAM-1 in HUVECs. Taken together, we suggest that SPC may contribute to atherosclerosis; thus SPC and its as yet unidentified target receptor offer a starting point for the development of a treatment for atherosclerosis.