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


METHODS
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.
Kaido
Toshimi
T
Department of Surgery, Otsu Municipal Hospital, Shiga, Japan. kaido3@hotmail.com
Oe
Hideaki
H
Imamura
Masayuki
M
D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000494:pharmacology*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D050796:STAT3 Transcription Factor; D012680:Sensitivity and Specificity; D015534:Trans-Activators / Q000187:drug effects* / Q000378:metabolism
D015415:Biomarkers; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D017228:Hepatocyte Growth Factor