Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea.
Inflammation. 2015;38(3):987-94. doi: 10.1007/s10753-014-0062-4.
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.
众所周知，分泌型 PLA2 家族 IIA（sPLA2-IIA）的表达水平在炎症性疾病中升高，脂多糖（LPS）上调人脐静脉内皮细胞（HUVEC）中 sPLA2-IIA 的表达。激活的因子 X（FX）是凝血级联反应中的重要酶，通过激活蛋白酶激活受体（PAR），影响各种细胞类型的细胞信号转导。在这里，FX 或 FXa 被检查对 HUVEC 和小鼠中 sPLA2-IIA 的表达和活性的影响。细胞或小鼠先用 FXa 处理，通过与 FXa 受体（有效细胞蛋白酶受体-1，EPR-1）相互作用，抑制 LPS 诱导的 sPLA2-IIA 的表达和活性。并且 FXa 抑制 LPS 诱导的胞质 PLA2（cPLA2）和细胞外信号调节激酶（ERK）1/2 的激活。因此，这些结果表明 FXa 可能通过抑制 cPLA2 和 ERK1/2 来抑制 LPS 介导的 sPLA2-IIA 的表达。
