EFFECTS OF SHORT AND LONG-TERM ETHANOL ON THE ACTIVATION OF SIGNAL TRANSDUCER AND ACTIVATOR TRANSCRIPTION FACTOR-3 IN NORMAL AND REGENERATING LIVER

Interleukin-6 (IL-6) induced activation of Signal Transducer and Activ ator Transcription Factor 3 (Stat 3) is a critical step in liver regen eration. Chronic ethanol consumption is known to increase the plasma c oncentration of IL-6, yet the ability of the liver to regenerate and t he regenerative induction of several IL-6 initiated events are impaire d in chronic alcoholic liver disease. We hypothesized that chronic eth anol consumption inhibits IL-6 dependent signal transduction. To test this hypothesis, the effect of ethanol on the Stat3 signal transductio n pathway was studied in the adult rat liver. In vitro treatment of fr eshly isolated normal adult rat hepatocytes with 50-100 mM ethanol for 30 min blocked IL-6-induced Stat3 activation. Long-term ethanol intak e in vivo significantly attenuated the activation of Stat3 induced eit her in vivo by partial hepatectomy or in vitro by IL-6. In contrast, s hort-term ethanol consumption enhanced the regenerative induction of S tat3 but inhibited IL-6 induced Stat3 activation. These data suggest t hat the inhibition of liver regeneration by chronic ethanol consumptio n is, at least in part, mediated by modulating the activation of Stat3 . (C) 1997 Academic Press.