title: NFkappaB inhibition decreases hepatocyte proliferation but does not alter apoptosis in obstructive jaundice.
abstract: BACKGROUND
  Cholestasis activates nuclear factor kappa B (NFkappaB), which is involved in both hepatocyte proliferation and apoptosis, depending on the cellular microenvironment. We hypothesized that NFkappaB inhibition would decrease hepatocyte proliferation and potentiate hepatocyte apoptosis in a rat model of extrahepatic biliary obstruction.
  
  
  OBJECTIVE
  To determine if NFkappaB inhibition concomitantly decreases hepatocyte proliferation and increases apoptosis in obstructive jaundice.
  
  
  METHODS
  Male Sprague-Dawley rats underwent either sham operation or bile-duct ligation (BDL) combined with portal vein injection of vehicle or 6 x 10(9) particles of an adenovirus carrying either the control luciferase or the IkappaB super-repressor (AdIkappaBSR) transgenes. Liver was harvested 3, 5, and 7 days after sham operation or BDL, and immunohistochemistry for proliferating cell nuclear antigen and terminal dUTP nick end-labeling was performed for detection of DNA synthesis and apoptosis, respectively.
  
  
  RESULTS
  Increased serum total bilirubin and hematoxylin and eosin-stained liver sections confirmed cholestasis in BDL animals. Western blot analysis demonstrated IkappaBSR protein expression in AdIkappaBSR-infected animals only. At day 7, NFkappaB inhibition decreased hepatocyte DNA synthesis in BDL rats compared to both adenovirus carrying the control luciferase and vehicle-treated controls. Apoptosis was increased in BDL vehicle-treated animals compared to sham-operation animals, but NFkappaB inhibition did not alter hepatocyte apoptosis in the BDL group.
  
  
  CONCLUSIONS
  In obstructive cholestasis, NFkappaB is required for hepatocyte proliferation, but does not augment apoptosis.
authors.affiliation: Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7081, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bird
authors.forename: Dalliah
authors.initials: D
authors.lastname: Black
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Lange
authors.forename: Charles M
authors.initials: CM
authors.lastname: Samson
authors.forename: Melissa
authors.initials: M
authors.lastname: Hayden
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Behrns
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001652:Bile Ducts / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D002455:Cell Division; D002779:Cholestasis / Q000473:pathology* / Q000628:therapy*; D004195:Disease Models, Animal; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D022781:Hepatocytes / Q000473:pathology*; D020672:I-kappa B Proteins / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D008156:Luciferases