Hyper-activated IRF-1 and STAT1 contribute to enhanced interferon stimulated gene (ISG) expression by interferon alpha and gamma co-treatment in human hepatoma cells

Xiao-Nan Zhang, Jiang-Xia Liu, Yun-Wen Hu, Hui Chen, Zheng-Hong Yuan

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Previous reports suggest that type I and type II Interferon can co-operatively inhibit some virus replication, e.g. HCV, SARS-CoV, HSV-1. To find out the molecular mechanism underlying this phenomenon, we analyzed the transcription profile stimulated by IFN-alpha and IFN-gamma in Huh-7 cells and found that the transcription of a subset of IFN stimulated genes (ISGs) including BclG, XAF1, TRAIL and TAP1 was enhanced when IFN-alpha and gamma were both present. Promoter analysis of BclG revealed that IRF-1 and STAT1 were both required in this process. Enhanced IRF-1/DNA complex formation was observed in interferon co-treatment group by gel shift analysis. Furthermore, IRF-1 activation was found to be generally required in this cluster of ISGs. STAT1 tyrosine phosphorylation was elevated by IFN combination treatment, however, only the hyper-transactivation of GAS but not ISRE was observed. In conclusion, hyper-activation of IRF-1 and elevated STAT1 dimer formation may be two general switches which contribute to a much more robust antiviral symphony against virus replication when type I and type II IFNs are co-administered.

Original languageEnglish
Pages (from-to)417-425
Number of pages9
JournalBiochimica et Biophysica Acta: international journal of biochemistry and biophysics
Volume1759
Issue number8-9
DOIs
Publication statusPublished - 22 Sep 2006
Externally publishedYes

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