ACTIVATION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION-3 (STAT3) EXPRESSION BY INTERFERON-GAMMA AND INTERLEUKIN-6 IN HEPATOMA-CELLS

Signal Transducer and Activator of Transcription 3 (Stat3) is a latent protein activated in response to various cytokines and growth factors . It is believed that Stat3 is a key signaling molecule involved in th e regulation of acute phase gene expression by interleukin 6 (IL-6) in hepatocytes. We report that both IL-6 and interferon gamma (IFN gamma ) up-regulate the expression of Stat3 on both mRNA and protein levels in rat and human hepatoma cells. The effect of IL-6 and IFN gamma on S tat3 mRNA expression was time- and dose-dependent. Other factors, incl uding IL-1, TNF alpha, EGF, Dexamethasone and PMA, did not have any ef fect on Stat3 mRNA expression. Moreover, we show that the rapid induct ion of Stat3 expression by IL-6 and IFN gamma was independent of ongoi ng protein synthesis, suggesting regulation by Stat3 and Stat1, respec tively. (C) 1995 Academic Press, Inc.