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

Abstract

Phospholipase A₂ IIA (PLA₂IIA), 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 PLA₂IIA expression level in these different models. The aim of this study was to investigate the modulatory effect of UDCA on the PLA₂IIA expression level at the cellular level. The HepG2 cells were selected to investigate the direct inhibitory effect of UDCA on PLA₂IIA expression level. The proinflammatory cytokines (interleukin-6 and tumor necrosis factor α) -induced PLA₂IIA 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 PLA₂IIA 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 PLA₂IIA expression level, in particular, as the protective action of UDCA in patients with chronic liver disease. (HEPATOLOGY 2005;41:896–905.)