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Expression and Function of the Lysophospholipids Receptors, S1P1 and LPA1, in Human Endothelial Cells and the Regulation of Inflammation‐Related Genes
Author(s) -
LIN CHIIOU,
Chen ChiungNien,
Wu HuaLin,
Lee Hsinyu
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a858-b
Subject(s) - microbiology and biotechnology , inflammation , umbilical vein , lysophosphatidic acid , chemotaxis , receptor , sphingosine 1 phosphate , monocyte , u937 cell , sphingosine , endothelium , endothelial stem cell , cell adhesion , lipid signaling , chemistry , biology , cell , immunology , cell culture , biochemistry , endocrinology , in vitro , genetics
Sphingosine 1‐phosphate (S1P) and lysophosphatidic acid (LPA) are bioactive lysophospholipid (LPL) ligands that bind endothelial differentiation gene (Edg) family G protein‐coupled receptors and have been implicated as important regulators in endothelial cells during inflammation processes. In this study, introduction of siRNA against S1P 1 or LPA 1 significantly suppressed S1P‐ or LPA‐upregulated ICAM‐1, IL‐8, and MCP‐1 mRNA expressions, and ICAM‐1 total protein and cell surface expressions in human umbilical vein endothelial cells (HUVECs). Moreover, U937 cells adhesion to S1P‐ or LPA‐treated HUVECs and THP‐1 cell chemotaxis toward S1P‐ or LPA‐treated HUVEC‐conditioned media was profoundly reduced by knocking down S1P 1 or LPA 1 in HUVECs. These results suggest that S1P 1 or LPA 1 mediates S1P‐ or LPA‐ induced ICAM‐1, IL‐8, and MCP‐1 gene expressions, which contribute to monocyte adhesion and chemoattraction toward the endothelium, thus facilitating inflammation processes. Our findings suggest the possible utilization of S1P 1 or LPA 1 as drug targets to treat severe inflammation.