Sphingosine 1-phosphate regulates inflammation-related genes in human endothelial cells through S1P1 and S1P3

Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid (LPL) ligand that binds endothelial differentiation gene (Edg) family G-protein-coupled receptors and has been implicated as an important regulator in endothelial cells during inflammation processes. In this study, we attempt to determine which S1P receptors mediating the inflammatory response in human endothelial cells. Our results indicated that introduction of siRNA against S1P1 significantly suppressed S1P-induced ICAM-1 mRNA, total protein, and cell surface expressions in human umbilical vein endothelial cells (HUVECs). Moreover, U937 cells adhesion to S1P-treated HUVECs was profoundly reduced by knock-down of S1P1 in HUVECs. By knock-down of S1P1 or S1P3 in HUVECs, S1P-enhanced IL-8, MCP-1 mRNA expression, and THP-1 cell chemotaxis toward S1P-treated HUVEC-conditioned media was profoundly reduced. These results suggested that S1P-induced inflammatory response genes expression is mediated through S1P1 and S1P3. Our findings suggest the possible utilization of S1P1 or S1P3 as drug targets to treat severe inflammation.