Background
Lysophosphatidylcholine (LPC), a derivative of phosphatidylcholine (PC) hydrolyzed by phospholipase A2 (PLA2), is reported to be increased in bile of the patients with pancreaticobiliary maljunction or intrahepatic cholelithiasis, both of which are major risk factors for biliary tract cancers with undefined etiology.
Conclusions
These data suggest that PLA2, which catalyzes the hydrolysis of PC to yield LPC and free fatty acid, is supposed to be an important etiological factor in BECs injury in pancreaticobiliary maljunction or intrahepatic cholelithiasis.
Methods
To investigate the influence of LPC on biliary epithelial cells (BECs), a human cholangiocarcinoma cell line HuCCT-1 and an immortalized human BECs line MMNK-1 were treated by LPC in vitro.
Results
The treatment of LPC exhibited cytotoxicity with significant induction of apoptosis. In addition to upregulation of Fas receptor mRNA, the activities of caspase-8 and -3 were significantly increased by LPC treatment. We also observed upregulation of Bax mRNA and significant activation of caspase-9. Interestingly, LPC significantly upregulated G2A, a member of transmembrane G protein-coupled receptor family at mRNA and protein levels, and 9-hydroxyoctadecaduenoic acid (9HODE), an oxidized free fatty acid that functions as a ligand for G2A dramatically reduced cell viability when treated together with LPC. Conclusions: These data suggest that PLA2, which catalyzes the hydrolysis of PC to yield LPC and free fatty acid, is supposed to be an important etiological factor in BECs injury in pancreaticobiliary maljunction or intrahepatic cholelithiasis.