title: Inhibitory effect of thrombin on the expression of secretory group IIA phospholipase A₂.
abstract: It is well known that the expression level of secretory group IIA phospholipase A(2) (sPLA(2)-IIA) is elevated in inflammatory diseases and lipopolysaccharide (LPS) up-regulates the expression of sPLA(2)-IIA in human umbilical vein endothelial cells (HUVECs). Recently, lower concentration thrombin could elicit anti-inflammatory responses in HUVECs. Here, the effects of lower concentration thrombin on the expression of sPLA(2)-IIA in LPS-stimulated HUVECs were investigated. Prior treatment of cells with thrombin (25-75 pM) inhibited LPS-induced sPLA(2)-IIA expression by activating its receptor, protease-activated receptor-1 (PAR-1). And pretreatment of cells with either PI3-kinase inhibitor (LY294002) or cholesterol depleting agent (methyl-β-cyclodextrin, MβCD) abolished the inhibitory activity of thrombin against sPLA(2)-IIA expression. Therefore, these results suggest that PAR-1 activation by lower concentration thrombin inhibited LPS mediated expression of sPLA(2)-IIA by PAR-1 and PI3-kinase-dependent manner in lipid raft on the HUVECs.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea. baejs@knu.ac.kr
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D015536:Down-Regulation; D015870:Gene Expression; D054501:Group II Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology* / Q000502:physiology; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D000924:Anticholesteremic Agents; D008070:Lipopolysaccharides; D009842:Oligopeptides; D044463:Receptor, PAR-1; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C508781:threonyl-phenylalanyl-leucyl-leucyl-arginyl-asparagine; D019869:Phosphatidylinositol 3-Kinases; D054501:Group II Phospholipases A2; D013917:Thrombin