NF-κB activation in non-parenchymal liver cells after partial hepatectomy in rats: possible involvement in expression of heparin-binding epidermal growth factor-like growth factor

Background/Aims: Nuclear factor (NF) κB activation plays a critical role in the initiation of liver growth after partial hepatectomy (PH). However, the issue of where specifically NF-κB is activated is unclear. We previously reported that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a hepatotrophic factor. The aims of this study were to identify NF-κB-activated cells and to clarify their involvement in HB-EGF expression after PH. Methods: Using rats, a two-thirds PH was performed, after which NF-κB-activated cells and HB-EGF-positive cells were identified by Southwestern histochemistry or immunohistochemistry. NF-κB binding activity and HB-EGF gene expression were analyzed in rat hepatocytes and non-parenchymal cells (NPC) in primary culture. Results: NF-κB was activated in Kupffer cells and sinusoidal endothelial cells prior to activation in hepatocytes. HB-EGF immunoreactivity was detected after NF-κB activation in the sinusoidal cells from those localized in the periportal zones of hepatic lobules. HB-EGF gene expression by tumor necrosis factor α was accompanied by an increase in NF-κB binding activity in NPC but not in hepatocytes in primary culture, which was abolished by pyrrolidine dithiocarbamate, an inhibitor of NF-κB activation. Conclusions: NF-κB was activated in NPC prior to activation in hepatocytes. NF-κB activation may be involved in HB-EGF expression in NPC after PH.