Inhibitory Effect of FXa on Secretory Group IIA Phospholipase A2.
It is well known that the expression level of secretory group IIA phospholipase A2 (sPLA2-IIA) is elevated in inflammatory diseases and lipopolysaccharide (LPS) upregulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Activated factor X (FXa) is an important enzyme in the coagulation cascade responsible for thrombin generation, and it influences cell signaling in various cell types by activating protease-activated receptors (PARs). Here, FX or FXa was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mouse. Prior treatment of cells or mouse with FXa inhibited LPS-induced expression and activity of sPLA2-IIA via interacting with FXa receptor (effective cell protease receptor-1, EPR-1). And FXa suppressed the activation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2 by LPS. Therefore, these results suggest that FXa may inhibit LPS-mediated expression of sPLA2-IIA by suppression of cPLA2 and ERK 1/2.
Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
Sae-Kwang
SK
Ku
Jong-Sup
JS
Bae
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism*; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000473:pathology; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012097:Repressor Proteins / Q000378:metabolism; D018805:Sepsis / Q000473:pathology; D015398:Signal Transduction; D000077022:Survivin
C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008070:Lipopolysaccharides; D012097:Repressor Proteins; D000077022:Survivin; D005170:Factor X; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D054501:Group II Phospholipases A2; D054513:Group IV Phospholipases A2; C516287:PLA2G2A protein, human; C516288:Pla2g2a protein, mouse; D015951:Factor Xa