SR- Bâ… Protects Against The Inflammatory Response Of S1P/S1PR2 Was Induced By Ox-LDl In Human Umbilical Vein Endothelial Cells

[Purpose] Endothelial dysfunction is a pivotal event in the development and progression of atherosclerosis. Oxidized low density lipoprotein(ox-LDL) can induce vascμlar endothelial injury and inflammation in vessel wall. Scavenger receptor class B typeⅠ(SR-BⅠ) is a high affinity receptor for high density lipoprotein(HDL) and mediates intracellular signal pathways, such as SR-B Ⅰ /PI3K/AKT. Sphingosine-1-phosphate exerts a variety of biolo Gαical action on different cells through its different receptors. In vascμlar endothelial cells, S1 P possesses reciprocal effects for inflammatory response by receptors S1PR1/3 and S1PR2. In this study we investigated the effects of SR-BⅠ/PI3K/AKT pathway on S1P/S1PR2-mediated pro-inflammatory response induced by ox-LDL in endothelial cells.[Methods] Cultured human umbilical vein endothelial cells(HUVECs) were treated with 60μg/ml of ox-LDL, and then treated with different concentrations of S1 P for 6h. The inhibitors of S1PR1/3(VPC23019), S1PR2(JTE-013), SR-B Ⅰ(BLT-1), PI3K(LY294002),Akt(MK2206) and e NOS(L-NAME) and transient transfection of SR-BⅠ were applied to intervene the effects. The protein expression levels of cytokines TNF-α, IL-1β and IL-10 were determined by Western blot and ELISA in cell and cell cμlture, respectively. The nuclear translocation of NF-κB were determined by immunofluorescence. [Results] The protein expression levels of cytokines TNF-α and IL-1β both in cell and in cell cμlture were significantly decreased, but IL-10 increased compared with control after treatment with S1 P and apo A-1, or transfection with SR-BⅠ. Nuclear translocation of NF-κB was also significantly reduced compared with control. The inhibitors BLT-1, LY294002,MK2206 and L-NAME attenuated the antagonist effect of apo A-1. [Conclusions] SR-BⅠinhibits the pro-inflammatory effect of S1P/S1PR2 on vascμlar endothelial cells, which may be associated with the PI3K/AKT/e NOS signaling pathway.