NFkappaB inhibition decreases hepatocyte proliferation but does not alter apoptosis in XXXX .

@entity3883 @entity648 @entity1711 @entity1977 @entity1448 @entity1710 @entity2876 @entity35
INTRODUCTION: 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 @entity35 model of @entity2876 . AIM: To determine if NFkappaB inhibition concomitantly decreases hepatocyte proliferation and increases apoptosis in @entity3883 . MATERIALS AND METHODS: Male @entity35 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 @entity1977 nick end-labeling was performed for detection of DNA synthesis and apoptosis, respectively. RESULTS: Increased serum total @entity648 and @entity1710 and @entity1711 -stained liver sections confirmed @entity1448 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 @entity35 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. CONCLUSION: In obstructive @entity1448 , NFkappaB is required for hepatocyte proliferation, but does not augment apoptosis.
