title: ATP-binding cassette sterol transporters are differentially expressed in normal and diseased human gallbladder.
abstract: OBJECTIVE
  Gallbladder epithelial cells (GBEC) are exposed to high cholesterol concentrations in bile, and export cholesterol via an ATP-binding cassette (ABC) transporter-mediated pathway in vitro. These findings suggest that aberrant expression and/or function of ABC sterol transporters may be associated with cholesterol-related gallbladder diseases (CAGD). In this study, we investigated the relative levels of the sterol transporters ABCA1, ABCG5, and ABCG8 in human gallbladders in CAGD, and the relationship between ABCA1 and inflammation.
  
  
  METHODS
  Expression of ABCA1, ABCG5, and ABCG8 was evaluated in 31 gallbladders with CAGD and 6 normal gallbladders by western blotting and immunohistochemistry. RT-PCR was used to measure ABCA1 mRNA expression. To investigate the relationship between ABCA1 and inflammation, wWestern blots were performed on cultured dog GBEC treated with lipopolysaccharide (LPS) using an anti-ABCA1 antibody.
  
  
  RESULTS
  Immunohistochemistry showed ABCA1 to be localized predominantly to the basolateral membrane, while ABCG8 formed a diffuse intracellular pattern at the apical pole of human GBEC. ABCA1 and ABCG8 expression was more prominent in GBEC that were surrounded by cholesterol-laden macrophages. ABCA1 and ABCG8 expression was increased in gallbladders with CAGD. Western blots showed increased ABCA1, ABCG5, and ABCG8 expression in CAGD. ABCA1 mRNA levels were increased in all gallbladders with CAGD. LPS treatment of cultured dog GBEC enhanced ABCA1 expression.
  
  
  CONCLUSIONS
  The sterol transporters ABCA1, ABCG5, and ABCG8 may play a role in the pathogenesis of human CAGD. Inflammation appears to be a key factor that increases ABCA1 expression and activity in the human gallbladder.
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Chucheon, Korea.
authors.forename: Jai Hoon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Ho Soon
authors.initials: HS
authors.lastname: Choi
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Jun
authors.forename: Kyo-Sang
authors.initials: KS
authors.lastname: Yoo
authors.forename: Jin
authors.initials: J
authors.lastname: Lee
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Yang
authors.forename: Rahul
authors.initials: R
authors.lastname: Kuver
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D002764:Cholecystitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005704:Gallbladder / Q000276:immunology* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D064286:ATP Binding Cassette Transporter 1; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008070:Lipopolysaccharides; D008074:Lipoproteins; D012333:RNA, Messenger; D002784:Cholesterol