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.