Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10769980 | Biochemical and Biophysical Research Communications | 2005 | 6 Pages |
Abstract
Recently, we have shown that SOCS-1/3 overexpression in hepatic cells abrogates signaling of type I interferons (IFN) which may contribute to the frequently observed IFN resistance of hepatitis C virus (HCV). IFN-λs (IL-28A/B and IL-29), a novel group of IFNs, also efficiently inhibit HCV replication in vitro with potentially less hematopoietic side effects than IFN-α because of limited receptor expression in hematopoietic cells. To further evaluate the potential of IFN-λs in chronic viral hepatitis, we examined the influence of SOCS protein expression on IFN-λ signaling. First, we show that hepatic cell lines express the IFN-λ receptor complex consisting of IFN-λR1 (IL-28R1) and IL-10R2. Whereas in mock-transfected HepG2 cells, IL-28A and IL-29 induced STAT1 and STAT3 phosphorylation, overexpression of SOCS-1 completely abrogated IL-28A and IL-29-induced STAT1/3 phosphorylation. Similarly, IL-28A and IL-29 induced mRNA expression of the antiviral proteins 2â²,5â²-OAS and MxA was abolished by overexpression of SOCS-1. In conclusion, we assume that despite antiviral properties of IFN-λs, their efficacy as antiviral agents may have similar limitations as IFN-α due to inhibition by SOCS proteins.
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Authors
Stephan Brand, Kathrin Zitzmann, Julia Dambacher, Florian Beigel, Torsten Olszak, George Vlotides, Sören T. Eichhorst, Burkhard Göke, Helmut Diepolder, Christoph J. Auernhammer,