CELLULAR-DISTRIBUTION OF NUCLEAR FACTOR-KAPPA-B BINDING-ACTIVITY IN RAT-LIVER

The cellular localization of nuclear factor kappa B (NF-kappaB) binding activity in rat liver has been investigated using electrophoretic mobility shift assay on extracts of highly purified hepatocytes and Kupffer cells obtained from liver perfused in vivo with collagenase. Constitutive NF-kappaB binding activity was demonstrated in nuclear extracts of control Kupffer cells, and this was not apparently influenced by injection of lipopolysaccharide (LPS) into rats 24 h before perfusion. In contrast, little nuclear NF-kappaB binding activity was present in hepatocytes from control animals, although there was detectable inactive, inhibitor-bound, NF-kappaB in the cytoplasm. However, nuclear NF-kappaB binding activity was increased in hepatocytes from LPS-treated animals and after in vitro culture of control rat hepatocytes. Thus NF-kappaB binding activity has been demonstrated in highly purified hepatocytes and appears to be inducible both in vivo and in vitro. These findings support a role for NF-kappaB in hepatocyte gene regulation which may be important in the modulation of the hepatic acute phase response.