title: Histamine restores biliary mass following carbon tetrachloride-induced damage in a cholestatic rat model.
abstract: BACKGROUND
  Bile duct ligation coupled with carbon tetrachloride induces apoptosis of large but not small cholangiocytes. Histidine decarboxylase regulates histamine synthesis. We have shown that: (i) cholangiocytes express histidine decarboxylase and secrete histamine and (ii) histamine stimulates biliary growth.
  
  
  OBJECTIVE
  To demonstrate that histidine decarboxylase/histamine regulates cholangiocyte homeostasis after carbon tetrachloride treatment.
  
  
  METHODS
  In vivo, normal and bile duct ligated rats were treated with saline or histamine (0.5mg/kg body weight) and given carbon tetrachloride by gavage 2 days before sacrifice. Serum, liver blocks and large cholangiocytes were obtained. Histidine decarboxylase, bile duct mass and proliferation were measured in liver sections and in cholangiocytes. Apoptosis was measured by immunohistochemistry and gene expression. Histamine levels were evaluated in serum. In vitro, large cholangiocytes were treated with carbon tetrachloride in the absence/presence of histamine before evaluating proliferation.
  
  
  RESULTS
  After bile duct ligation there was enhanced ductal mass, histidine decarboxylase expression and serum histamine levels. Carbon tetrachloride treatment enhanced biliary apoptosis, and decreased histidine decarboxylase and serum histamine levels and biliary proliferation, changes that were restored by histamine. In vitro, cholangiocytes treated with carbon tetrachloride had a lower proliferative capacity that was reversed when cells were pre-treated with histamine.
  
  
  CONCLUSIONS
  Histidine decarboxylase may be a key regulator of cholangiocyte homeostasis during biliary injury.
authors.affiliation: Medicine, Texas A&M University HSC, Temple, TX, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Scott & White Digestive Disease Research Center, BaylorScott and White, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Hargrove
authors.affiliation: Scott & White Digestive Disease Research Center, BaylorScott and White, USA.
authors.forename: Allyson
authors.initials: A
authors.lastname: Graf
authors.affiliation: Scott & White Digestive Disease Research Center, BaylorScott and White, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Kennedy
authors.affiliation: Scott & White Digestive Disease Research Center, BaylorScott and White, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Hodges
authors.affiliation: Scott & White Digestive Disease Research Center, BaylorScott and White, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Harris
authors.affiliation: Scott & White Digestive Disease Research Center, BaylorScott and White, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Francis
authors.affiliation: Department of Gastroenterology, Yamagata University Faculty of Medicine, Japan; CREST, Japan Science and Technology Agency, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.affiliation: Research, Central Texas Veteran's Health Care System, USA; Scott & White Digestive Disease Research Center, BaylorScott and White, USA; Medicine, Texas A&M University HSC, Temple, TX, USA. Electronic address: hfrancis@medicine.tamhsc.edu.
authors.forename: Heather
authors.initials: H
authors.lastname: Francis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001652:Bile Ducts / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D002251:Carbon Tetrachloride; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D006632:Histamine / Q000097:blood*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D008026:Ligation; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D051381:Rats; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism*
chemical_list: D011968:Receptors, Histamine; D006632:Histamine; D002251:Carbon Tetrachloride; D006640:Histidine Decarboxylase
keywords: Biliary epithelium; Damage; Homeostasis; Mitosis; Restoration