NFκB inhibition decreases hepatocyte proliferation but does not alter apoptosis in obstructive jaundice

Mark A. Bird, Dalliah Black, Patricia A. Lange, Charles M. Samson, Melissa Hayden, Kevin E. Behrns

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Introduction. Cholestasis activates nuclear factor kappa B (NFκB), which is involved in both hepatocyte proliferation and apoptosis, depending on the cellular microenvironment. We hypothesized that NFκB inhibition would decrease hepatocyte proliferation and potentiate hepatocyte apoptosis in a rat model of extrahepatic biliary obstruction. Aim. To determine if NFκB inhibition concomitantly decreases hepatocyte proliferation and increases apoptosis in obstructive jaundice. Materials and methods. Male Sprague - Dawley rats underwent either sham operation or bile-duct ligation (BDL) combined with portal vein injection of vehicle or 6 × 109 particles of an adenovirus carrying either the control luciferase or the IκB super-repressor (AdIκBSR) 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 IκBSR protein expression in AdIκBSR-infected animals only. At day 7, NFκB 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 NFκB inhibition did not alter hepatocyte apoptosis in the BDL group. Conclusion. In obstructive cholestasis, NFκB is required for hepatocyte proliferation, but does not augment apoptosis.

Original languageEnglish
Pages (from-to)110-117
Number of pages8
JournalJournal of Surgical Research
Issue number2
StatePublished - Oct 2003


  • Apoptosis
  • Bile-duct ligation
  • Cholestasis
  • NFκB
  • Proliferation


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