NF-kappaB activation in Kupffer cells after partial hepatectomy

Abstract

The transcription factor nuclear factor-kappaB (NF-kappaB) is activated during liver regeneration after partial hepatectomy. However, the physiological role and cellular localization of NF-kappaB activation are unresolved. In this study, we used an adenoviral vector expressing a mutated form of IkappaBalpha to inhibit NF-kappaB activity during liver regeneration. After partial hepatectomy in mice, introduction of Ad5IkappaB, but not a control virus (Ad5GFP), resulted in increased liver injury and decreased hepatocyte proliferation. Hepatocyte apoptosis was not observed. To investigate the kinetics and cellular localization of NF-kappaB-induced transcription during liver regeneration, we generated a transgenic mouse expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappaB cis elements (cis-NF-kappaB-EGFP). During liver regeneration, EGFP expression was detected within 12 h and was primarily located in Kupffer cells. Our data demonstrate that activation of NF-kappaB initially occurs in Kupffer cells after partial hepatectomy in mice.