Biochemical and Biophysical Research Communications, Vol.363, No.4, 1001-1008, 2007
Lysophosphatidic acid regulates inflammation-related genes in human endothelial cells through LPA(1) and LPA(3)
Lysophosphatidic acid (LPA) is a low-molecular-weight lysophospholipid (LPL), which regulates endothelial cells participating in inflammation processes via interactions with endothelial differentiation gene (Edg) family G protein-coupled receptors. In this study, we attempted to determine which LPA receptors mediate the inflammatory response in human endothelial cells. Introduction of siRNA against LPA(1) significantly suppressed LPA-induced ICAM-I mRNA, total protein, and cell surface expressions, and subsequent U937 monocyte adhesion to LPA-treated human umbilical endothelial cells (HUVECs). By knock down of LPA(1) and LPA(3) in HUVECs, LPA-enhanced IL-1 beta mRNA expression was significantly attenuated. Moreover, LPA(1) and LPA(3) siRNA also inhibited LPA-enhanced IL-1-dependent long-term IL-8 and MCP-1 mRNA expression, and subsequent THP-1 cell chemotaxis toward LPA-treated HUVEG conditioned media. These results suggest that the expression of LPA-induced inflammatory response genes is mediated by LPA(1) and LPA(3). Our findings suggest the possible utilization of LPA(1) or LPA(3) as drug targets to treat severe inflammation. (C) 2007 Elsevier Inc. All rights reserved.