IL–6 and IL–1 enhance hepatic expression of ALR (Augmenter of Liver Regeneration)

Liver Regneration is a complex process that involves many factors e.g. cytokines, growth factors and hormones. Among the hepatotrophic factors Augmenter of Liver Regeneration (ALR) has been shown to play an important role during liver regeneration. Additionally, increased ALR levels were detected for various types of acute liver diseases, and in addition we could find increased expression of ALR in livers from patients with cirrhosis, hepatocellular and cholangiocellular carcinoma. Furthermore, cytokines and growth factors have been demonstrated to play a significant role in cirrhosis and in hepatocellular carcinoma (HCC). The goal of our study was to investigate whether these factors may regulate the expression of ALR. Therefore, using primary human hepatocytes and hepatoma cell lines we investigated the effect of various cytokines (IL–1, IL–6, TNFα) and growth factors (HGF, EGF, TGF, KGF, PDGF) on the expression of ALR. Using RT-PCR, we found increased expression of ALR after 24h of exposure only with IL–1, IL–6 and a combination of both. Results from quantitative RT-PCR was further confirmed by western Blot analysis showing significant enhanced ALR protein levels after treatment of HepG2 with IL–1 and IL–6 (induced 2 fold over the control). Application of either IL–1 or IL–6 alone demonstrated slightly induced ALR expression. Therefore, we assumed that ALR might be regulated by cytokines (IL–1 and IL–6) in liver regeneration as well as cirrhosis and hepatocarcinogenesis. Further studies to elucidate the regulation mechanism are under investigation.

ALR - HCC - Liver regeneration - cirrhosis - cytokines