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 the 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 Stat3 mRNA expression was time- and dose-dependent. Other factors, including IL-1, TNF alpha, EGF, Dexamethasone and PMA, did not have any effect on Stat3 mRNA expression. Moreover, we show that the rapid induction of Stat3 expression by IL-6 and IFN gamma was independent of ongoing protein synthesis, suggesting regulation by Stat3 and Stat1, respectively.