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

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.