Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells.

磷脂酶A(2)IIA(PLA2 IIA)在花生四烯酸代谢和炎症中起关键作用，在多种病理条件下，包括多发性胆固醇结石患者的胆汁和胆汁，肝硬变大鼠的肝和肾，以及化学致癌物治疗的动物的结肠组织中，磷脂酶A(2)IIA都有上调。给予熊去氧胆酸(UDCA)可部分降低不同模型大鼠肝组织中PLA2 IIA的表达水平。本研究的目的是从细胞水平探讨UDCA对PLA2 IIA表达水平的调节作用。以人肝癌细胞株HepG2为研究对象，观察UDCA对细胞内PLA2(2)IIA表达的直接抑制作用。UDCA可部分抑制促炎症细胞因子(白介素6和肿瘤坏死因子α)诱导的肝癌细胞中PLAIIA的表达，且呈剂量依赖关系。UDCA对促炎症细胞因子诱导的LA(2)IIA表达的影响发生在转录水平。此外，在测试的胆汁酸中，这种抑制作用是UDCA所特有的。综上所述，本研究支持花生四烯酸代谢和PLA(2)IIA表达水平的可能改变，尤其是UDCA对慢性肝病患者的保护作用。

Phospholipase A(2) IIA (PLA(2)IIA), which plays a crucial role in arachidonic acid metabolism and in inflammation, is upregulated under various pathological conditions, including in the gallbladder and gallbladder bile from patients with multiple cholesterol gallstones, in the liver and kidney of rats with cirrhosis, as well as in the colonic tissue of animals treated with a chemical carcinogen. The administration of ursodeoxycholic acid (UDCA) partially attenuated the PLA(2)IIA expression level in these different models. The aim of this study was to investigate the modulatory effect of UDCA on the PLA(2)IIA expression level at the cellular level. The HepG2 cells were selected to investigate the direct inhibitory effect of UDCA on PLA(2)IIA expression level. The proinflammatory cytokines (interleukin-6 and tumor necrosis factor alpha)-induced PLA(2)IIA expression in HepG2 cells was partially inhibited by the presence of UDCA in a dose-dependent fashion. The effect of UDCA on proinflammatory cytokines-induced PLA(2)IIA expression occurred at the transcriptional level. In addition, among the bile acids tested, this inhibitory effect was UDCA-specific. In conclusion, this study supports the possible alteration of arachidonic acid metabolism and PLA(2)IIA expression level, in particular, as the protective action of UDCA in patients with chronic liver disease.