Phorbol ester-mediated down-regulation of an interferon-inducible gene

Interferons (IFNs) induce the expression of a variety of cellular RNAs and inhibit phorbol ester induction of other genes. Experiments reported here indicate that phorbol esters can also specifically inhibit the expression of an IFN-induced RNA (IFN-IND-1). Phorbol esters exert their effects by inhibiting IFN-induced transcription of the gene that encodes IFN-IND-1 (ISG-54K); inhibitors of protein synthesis reverse the effects of these compounds. The actions of phorbol esters are only seen in those types of cultured cells where cycloheximide in the presence of IFN prevents long term IFN treatment of cells from inducing a "desensitized state." In desensitized cells, IFN is not able to reinduce the transcription of the RNA. Our results indicate that a protein kinase C-dependent pathway requiring protein synthesis may be one mechanism by which IFN is able to down regulate the transcription of genes whose expression it initially induces.