Sphingosine 1-phosphate regulates inflammation-related genes in human endothelial cells through S1P1 and S1P3
Sphingosine 1-phosphate regulates inflammation-related genes in human endothelial cells through S1P1 and S1P3
复制标题
DOI：
10.1016/j.bbrc.2007.02.043
复制
发表时间：
2007-04-20
影响因子：
3.1
通讯作者：
Lee, Hsinyu
中科院分区：
文献类型：
--
作者：
Lin, Chi-Iou;Chen, Chiung-Nien;Lee, Hsinyu
鞘氨醇1-磷酸（S1 P）是一种生物活性溶血磷脂（LPL）配体，其结合内皮分化基因（Edg）家族G-蛋白偶联受体，并且已被认为是炎症过程中内皮细胞中的重要调节剂。在这项研究中，我们试图确定哪些SIP受体介导的炎症反应在人内皮细胞。我们的结果表明，引入针对SIP的siRNA可显着抑制SIP诱导的人脐静脉内皮细胞（HUVEC）中ICAM-I mRNA、总蛋白和细胞表面表达。此外，U937细胞与SIP处理的HUVECs的粘附通过在HUVECs中敲低S1 P而显著降低。通过在HUVEC中敲低S1 P（3）或S1 P（3），S1 P增强的IL-8、MCP-1 mRNA表达和THP-1细胞对SIP处理的HUVEC条件培养基的趋化性被显著降低。这些结果表明，SIP诱导的炎症反应基因的表达是通过S1 P（1）和S1 P（3）介导的。我们的研究结果表明，可能利用S1 P或S1 P（3）作为治疗严重炎症的药物靶点。(c)2007年爱思唯尔公司All rights reserved.
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 SIP receptors mediating the inflammatory response in human endothelial cells. Our results indicated that introduction of siRNA against SIP, significantly suppressed SIP-induced ICAM-I mRNA, total protein, and cell surface expressions in human umbilical vein endothelial cells (HUVECs). Moreover, U937 cells adhesion to SIP-treated HUVECs was profoundly reduced by knock-down of S1P, in HUVECs. By knock-down of S1P(3) or S1P(3) in HUVECs, S1P-enhanced IL-8, MCP-1 mRNA expression, and THP-l cell chemotaxis toward SIP-treated HUVEC-conditioned media was profoundly reduced. These results suggested that SIP-induced inflammatory response genes expression is mediated through S1P(1) and S1P(3). Our findings suggest the possible utilization of S1P, or S1P(3) as drug targets to treat severe inflammation. (c) 2007 Elsevier Inc. All rights reserved.