Interleukin-6 augments hepatocyte growth factor-induced liver regeneration; involvement of STAT3 activation

Hepatogastroenterology. 2004 Nov-Dec;51(60):1667-70.

Abstract

Background/aims: In liver regeneration, quiescent hepatocytes need to be primed before they can fully respond to growth factors such as hepatocyte growth factor (HGF). Recently, interleukin-6 (IL-6) has been shown to play an important role in initiating liver regeneration via activating signal transducer and activator of transcription 3 (STAT3). We therefore investigated the effect of IL-6 on liver regeneration and examined STAT3 activation following IL-6 and/or HGF treatment in rats.

Methodology: The animals underwent portal branch ligation (PBL) of the left lateral and median branches. They were intravenously treated with either IL-6 (500 microg/kg), HGF (50 microg/kg), both, or vehicle alone on and every 12 h after PBL. The degree of compensatory hypertrophy in unoccluded lobes was examined by measuring the wet weight ratios of the unoccluded lobes to the whole liver and the 5-bromo-2'-deoxyuridine labeling index of hepatocytes in each group. STAT3 expression in regenerating liver was examined by Western blotting and immunohistochemistry.

Results: Coadministration of IL-6 and HGF most effectively increased both the wet weight of the unoccluded lobes and the hepatocellular DNA synthesis. HGF as well as IL-6-treated animals showed moderate STAT3 activation in hepatocytes throughout the experiment.

Conclusions: IL-6 augmented HGF-induced liver regeneration and hepatocellular replication. Liver regeneration stimulated by HGF treatment may be closely involved with STAT3 activation in a different manner induced by IL-6 treatment.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biomarkers
  • Blotting, Western
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Drug Interactions
  • Hepatocyte Growth Factor / pharmacology*
  • Immunohistochemistry
  • Interleukin-6 / pharmacology*
  • Ligation
  • Liver Cirrhosis, Experimental / drug therapy*
  • Liver Cirrhosis, Experimental / pathology
  • Liver Regeneration / drug effects*
  • Liver Regeneration / physiology
  • Male
  • Random Allocation
  • Rats
  • Rats, Inbred F344
  • Reference Values
  • STAT3 Transcription Factor
  • Sensitivity and Specificity
  • Trans-Activators / drug effects*
  • Trans-Activators / metabolism

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • Interleukin-6
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Trans-Activators
  • Hepatocyte Growth Factor