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Involvement of IL-1beta and IL-10 in IFN-alpha-mediated antiviral gene induction in human hepatoma cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2002 Jun 07; Vol. 294 (2), pp. 414-22. - Publication Year :
- 2002
-
Abstract
- Crosstalk between interferons (IFNs) and several cytokines is likely to play an important role in viral clearance in chronic hepatitides B and C. We investigated the influence of this phenomenon on IFN-inducible antiviral gene expression in HuH-7 human hepatoma cells. HuH-7 cells were treated with IFN-alpha in the absence or presence of interleukin-1beta (IL-1beta) or IL-10 and the expression of antiviral genes such as 2(')5(')-oligoadenylate synthetase (2(')5(')-OAS) and double-stranded RNA-dependent protein kinase (PKR), as well as activation of signal transducer and activator of transcription 1 (STAT1), a key step for relaying the IFN-alpha signals, was analyzed by Northern blotting, Western blotting, and the reporter gene transfection assay. IL-1beta potentiated IFN-alpha-induced 2(')5(')-OAS and PKR gene expression, similar to expression of the transfected reporter genes containing the IFN-stimulated regulatory elements, while IL-10 suppressed IFN-alpha-stimulated gene expression. With regard to IFN-alpha signaling, IL-1beta enhanced both tyrosine and serine phosphorylation of STAT1 through p38 mitogen-activated protein kinase activation. In contrast, IL-10 inhibited IFN-alpha-mediated tyrosine phosphorylation of STAT1 by induction of a Janus kinase inhibitor, JAB. IL-1beta and IL-10 interact with IFN-alpha to up- and down-regulate antiviral gene expression, respectively, by modulating STAT1 activation induced by IFN-alpha.<br /> (c) 2002 Elsevier Science (USA).)
- Subjects :
- 2',5'-Oligoadenylate Synthetase biosynthesis
Blotting, Northern
Blotting, Western
Carcinoma, Hepatocellular immunology
DNA-Binding Proteins metabolism
Gene Expression drug effects
Gene Expression Regulation immunology
Genes, Reporter
Humans
Interferon-alpha pharmacology
Interleukin-1 pharmacology
Interleukin-10 pharmacology
Protein Biosynthesis
STAT1 Transcription Factor
Signal Transduction drug effects
Signal Transduction physiology
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Trans-Activators metabolism
Transcriptional Activation
Transfection
Tumor Cells, Cultured
eIF-2 Kinase biosynthesis
Carcinoma, Hepatocellular metabolism
Gene Expression Regulation drug effects
Interferon-alpha metabolism
Interleukin-1 metabolism
Interleukin-10 metabolism
Repressor Proteins
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 294
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 12051728
- Full Text :
- https://doi.org/10.1016/S0006-291X(02)00502-8