NFκB prevents apoptosis and liver dysfunction during liver regeneration

Although NF kappa B binding activity is induced during liver regeneration after partial hepatectomy, the physiological consequence of this induction is unknown. We have assessed the role of NF kappa B during liver regeneration by delivering to the liver a superrepressor of NF kappa B activity using an adenoviral vector expressing a mutated form I kappa B alpha. This adenovirus (Ad5I kappa B) was almost exclusively expressed in the liver and inhibited NP kappa B DNA binding activity and transcriptional activity in cultured cells as well as in the liver in vivo. After partial hepatectomy, infection with Ad5I kappa B, but not a control adenovirus (Ad5LacZ), resulted in the induction of massive apoptosis and hepatocytes as demonstrated by histological staining and TUNEL analysis, in addition, infection with Ad5I kappa B but not Ad5LacZ decreased the mitotic index after partial hepatectomy, These two phenomena, increased apoptosis and failure to progress through the cell cycle, were associated with liver dysfunction in animals infected with the Ad5I kappa B but not Ad5LacZ, as demonstrated by elevated serum bilirubin and ammonia levels, Thus, the induction of NF kappa B during liver regeneration after partial hepatectomy appears to be a required event to prevent apoptosis and to allow for normal cell cycle progression.