These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Role of ISGF3 in modulating the anti-hepatitis B virus activity of interferon-alpha in vitro.
    Author: Zhang Q, Wang Y, Wei L, Jiang D, Wang JH, Rao HY, Zhu L, Chen H, Fei R, Cong X.
    Journal: J Gastroenterol Hepatol; 2008 Nov; 23(11):1747-61. PubMed ID: 17559358.
    Abstract:
    BACKGROUND AND AIM: Although interferon-alpha (IFN-alpha) is an effective treatment for hepatitis B virus (HBV) infection, its precise mechanism of action has not been identified. In this study, we investigated the role of signal transduction pathways in the activation of anti-HBV responses mediated by IFN-alpha. METHODS: Using an oligo microarray, we found that four genes in the IFN-alpha signal pathway were markedly upregulated by IFN-alpha in human hepatoma cells regardless of whether they had been transfected with a plasmid containing the HBV genome: signal transducers and activators of transcription 1 (STAT1), interferon regulatory factor-9 (IRF-9, also called ISGF3gamma or P48), IFN-alpha-inducible protein 15 (IFI-15) and IFN-alpha-inducible protein 6-16 (IFI-6-16). We also investigated the role of IFN-stimulated gene factor3 (ISGF3) complex in IFN-alpha-mediated anti-HBV responses in human hepatoma cells by measuring the mRNA of the three genes within ISGF3 (STAT1, STAT2 and IRF-9) using semiquantitative reverse-transcription PCR (RT-PCR), and expression of the three proteins by western blot, and the mRNA and protein of dsRNA-dependent protein kinase (PKR). RESULTS: STAT1, STAT2, IRF-9 and PKR mRNA as well as protein levels were upregulated by IFN-alpha treatment. When cells were pretreated with genistein, STAT1, STAT2 and IRF-9 mRNA levels remained unchanged after IFN-alpha stimulation, but PKR mRNA levels decreased, and the expression of the STAT1, P-STAT2, IRF-9 and PKR proteins decreased. Levels of HBV DNA decreased in the supernatants of cells treated with IFN-alpha, while ISGF3 levels increased. The quantity of HBV DNA remained unchanged by pretreating with genistein. CONCLUSIONS: These observations suggested that the Janus tyrosine kinase-STAT (JAK-STAT) pathway may play a major role in mediating the effects of IFN-alpha against HBV, and that ISGF3 might be a key factor.
    [Abstract] [Full Text] [Related] [New Search]