Interferon-induced gene expression and signaling in human hepatoma cell lines

Background/Aim: Interferon(IFN)-alpha alone or combined with other antivira l substances has been extensively used for the treatment of viral infection s of the liver. Since the molecular mechanisms of IFN action in liver cells are relatively poorly characterized, we studied IPN-induced gene expressio n and signaling in human hepatoma, HepG2 and HuH7 cell lines. Methods/Results: IFN binding to its specific cell surface receptor leads to activation of the Janus family tyrosine kinase (JAK) - signal transducer a nd activator of transcription (STAT) pathway. We observed that in HepG2 and HuH7 cells IFN-inducible genes were upregulated by IFNs, but relatively hi gh concentrations of IFN-alpha were needed to turn on MxA (an antiviral gen e) and MxB gene expression. The basal expression of IFN-alpha receptor (IFN AR1 and IF-NAR2) JAK1 and TYK2 mRNAs was readily detectable, and their expr ession was not significantly altered by treatment with either IFN-alpha or IFN-gamma. Hepatoma cells possessed relatively low basal expression levels of IFN signaling molecules STAT1, STAT2 and p48, but their expression was s trongly upregulated by both types of IFNs, Pretreatment of HepG2 or HuH7 wi th low IFN-gamma doses, followed by stimulation with IFN-alpha, resulted in a marked enhancement of the formation of IFN-alpha -specific signaling com plex ISGF3. Conclusion: The results indicate positive feedback mechanisms in the IFN si gnaling system in hepatoma cells.