title: Partial characterization of proapoptotic action of biliary deteriorated lipids on biliary epithelial cells in pancreaticobiliary diseases.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Pharmaceutical Services, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujita
authors.forename: Akiko
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Kasumi
authors.initials: K
authors.lastname: Otoshi
authors.forename: Takanori
authors.initials: T
authors.lastname: Taogoshi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kimura
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Kishikawa
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kodama
authors.forename: Keishi
authors.initials: K
authors.lastname: Kanno
authors.forename: Kenji
authors.initials: K
authors.lastname: Kihira
authors.forename: Susumu
authors.initials: S
authors.lastname: Tazuma
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001659:Biliary Tract; D001660:Biliary Tract Diseases / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D004847:Epithelial Cells; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D010182:Pancreatic Diseases / Q000378:metabolism* / Q000401:mortality; D054467:Phospholipases A2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008244:Lysophosphatidylcholines; D054467:Phospholipases A2
keywords: Biliary epithelial cells; Intrahepatic cholelithiasis; Lysophosphatidylcholine; Pancreaticobiliary maljunction; Phospholipase A2