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 S1P(1) 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 S1P(1) in HUVECs. By knock-down of S1P(1) or S1P(3) 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 S1P(1) and S1P(3). Our findings suggest the possible utilization of S1P(1) or S1P(3) as drug targets to treat severe inflammation.
Lin
Chi-Iou
CI
Institute of Zoology, National Taiwan University, Taipei 106, Taiwan, ROC.
Chen
Chiung-Nien
CN
Lin
Po-Wei
PW
Lee
Hsinyu
H
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D018836:Inflammation Mediators; D008246:Lysophospholipids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; D018799:Intercellular Adhesion Molecule-1; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C032881:lysophosphatidic acid