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

✍ Scribed by Tadashi Ikegami; Yasushi Matsuzaki; Sugano Fukushima; Junichi Shoda; Jean Luc Olivier; Bernard Bouscarel; Naomi Tanaka

Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
806 KB
Volume
41
Category
Article
ISSN
0270-9139

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✦ Synopsis

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 ␣) -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. (HEPATOLOGY 2005;41:896-905.) C hanges in prostaglandin levels derived from arachidonic acid have been linked to hemodynamic alterations in patients with cirrhosis. One of the rate-limiting steps in the synthesis of prostaglandins is the release of arachidonic acid from membrane phospholipids by the phospholipase A 2 (PLA 2 ) enzyme. It has been reported that a secreted type of PLA 2 , PLA 2 IIA, which

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