title: gamma-Interferon inhibits secretin-induced choleresis and cholangiocyte proliferation in a murine model of cirrhosis.
abstract: OBJECTIVE
  Cholangiocyte proliferation is associated with increased secretin receptor gene expression and secretin-induced choleresis. Since gamma-interferon has antiproliferative effects, we tested the hypothesis that gamma-interferon inhibits ductal proliferation and secretin-stimulated choleresis associated with cirrhosis.
  
  
  METHODS
  Mice were treated with 0.1 ml of 25% carbon tetrachloride intraperitoneally twice weekly and 5% alcohol in drinking water for 12 weeks to induce cirrhosis and subsequently gamma-interferon 10(5) intramuscularly was administered daily for 10 weeks. We measured the effects of carbon tetrachloride and gamma-interferon on liver collagen content by morphometric analysis and hydroxyproline content. We measured the effects of gamma-interferon on ductal mass by morphometry and on ductal secretion by assessment of secretin receptor gene expression and secretin-induced choleresis.
  
  
  RESULTS
  Compared to controls, there was an increase in liver hydroxyproline content of carbon tetrachloride-treated mice with histologic evidence of cirrhosis. Gamma-interferon treatment significantly decreased collagen liver content with loss of histologic features of cirrhosis. Morphometry revealed an increased number of bile ducts in cirrhotic mice as compared to controls or cirrhotics who received gamma-interferon. Secretin receptor mRNA levels were higher in cirrhotic mice compared to controls but this increase was inhibited by gamma-interferon. Secretin stimulated ductal secretion in cirrhotic mice but not control or cirrhotic mice who received gamma-interferon.
  
  
  CONCLUSIONS
  We have established a murine model for cirrhosis and have shown, consistent with our hypothesis, that gamma-interferon decreases collagen content, ductal mass and secretin-induced choleresis incirrhotic mice.
authors.affiliation: Department of Internal Medicine, Scott & White Hospital, Temple, TX, USA.
authors.forename: G
authors.initials: G
authors.lastname: Alpini
authors.forename: I
authors.initials: I
authors.lastname: Elias
authors.forename: S S
authors.initials: SS
authors.lastname: Glaser
authors.forename: R E
authors.initials: RE
authors.lastname: Rodgers
authors.forename: J L
authors.initials: JL
authors.lastname: Phinizy
authors.forename: W E
authors.initials: WE
authors.lastname: Robertson
authors.forename: H
authors.initials: H
authors.lastname: Francis
authors.forename: J
authors.initials: J
authors.lastname: Lasater
authors.forename: M
authors.initials: M
authors.lastname: Richards
authors.forename: G D
authors.initials: GD
authors.lastname: LeSage
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics; D012633:Secretin / Q000494:pharmacology*
chemical_list: D001639:Bicarbonates; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin; D007371:Interferon-gamma; D003094:Collagen; D002251:Carbon Tetrachloride