IRF-1 expression in normal human epidermal keratinocytes.

Interferon gamma (IFN-gamma) is a potent inducer of cell growth arrest in human epidermal keratinocytes. Interferon regulatory factor-1 (IRF-1), an interferon-inducible gene, is a mediator of interferon action. It has also been suggested that IRF-1 may have a functional role as a tumor suppressor gene and may be associated with the antiproliferative effect of IFN-gamma. We examined the expression of IRF-1 mRNA in normal human epidermal keratinocytes (NHEK). Northern blot analysis demonstrated an increased expression of IRF-1 mRNA by IFN-gamma in NHEKs. This increased expression of IRF-1 mRNA by IFN-gamma was not blocked by treatment with cycloheximide, but was abolished by treatment with actinomycin D. In addition, neither pretreatment with TPA, a protein kinase C (PKC) activator, nor treatment with H7, a PKC inhibitor, affected the induction of IRF-1 mRNA by IFN-gamma. These results indicate that IFN-gamma-induced IRF-1 mRNA in NHEKs is transcriptional and PKC-independent.