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. 1990 Aug;1(9):707–713. doi: 10.1091/mbc.1.9.707

Characterization of two independent mechanisms by which interferon-induced gene expression is down regulated.

H Akai 1, A C Larner 1
PMCID: PMC361638  PMID: 2127700

Abstract

Interferons (IFNs) induce the expression of a variety of cellular RNAs. Phorbol esters can inhibit IFN-induced expression of some of these RNAs, including ISG-54K. The actions of phorbol esters on IFN-activated ISG-54K transcription are cell specific and are reversed by inhibitors of protein synthesis. In those cell lines in which phorbol esters inhibit IFN-induced ISG-54K transcription, prolonged IFN exposure also induces a "desensitized state" such that further IFN exposure no longer induces ISG-54K expression. IFN-induced desensitization is also reversed by inhibitors of protein synthesis. Experiments are described to determine whether the mechanism by which phorbol esters inhibit IFN-activated ISG-54K expression is the same as the mechanism by which prolonged exposure to IFN makes cells refractory to further induction of ISG-54K expression. Cultured cells treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) for 72 h are desensitized to phorbol esters such that further addition of phorbols does not inhibit IFN-induced ISG-54K expression. In both naive and TPA-desensitized human fibroblasts or WISH cells, prolonged IFN treatment induced a desensitized state that was reversible by cycloheximide. This observation suggests that the mechanisms by which prolonged IFN treatment and phorbol esters inhibit ISG-54K expression are independent.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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