Lysophosphatidic acid regulates inflammation-related genes in human endothelial cells through LPA1 and LPA3.
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.
Lin
Chi-Iou
CI
Institute of Zoology, National Taiwan University, Taipei 106, Taiwan, ROC.
Chen
Chiung-Nien
CN
Lin
Po-Wei
PW
Chang
King-Jen
KJ
Hsieh
Fong-Jou
FJ
Lee
Hsinyu
H
D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008246:Lysophospholipids / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*
D018932:Chemokine CCL2; D007375:Interleukin-1; D016209:Interleukin-8; D008246:Lysophospholipids; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid; C508645:monocyte chemoattractant protein 1 (66-77); D018799:Intercellular Adhesion Molecule-1; C032881:lysophosphatidic acid