Lysophosphatidic acid regulates inflammation-related genes in human endothelial cells through LPA1 and LPA3
Journal
Biochemical and Biophysical Research Communications
Journal Volume
363
Journal Issue
4
Pages
1001-1008
Date Issued
2007
Author(s)
Abstract
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 LPA1 significantly suppressed LPA-induced ICAM-1 mRNA, total protein, and cell surface expressions, and subsequent U937 monocyte adhesion to LPA-treated human umbilical endothelial cells (HUVECs). By knock down of LPA1 and LPA3 in HUVECs, LPA-enhanced IL-1beta mRNA expression was significantly attenuated. Moreover, LPA1 and LPA3 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 HUVEC-conditioned media. These results suggest that the expression of LPA-induced inflammatory response genes is mediated by LPA1 and LPA3. Our findings suggest the possible utilization of LPA1 or LPA3 as drug targets to treat severe inflammation.
SDGs
Type
journal article