Induction by interferon-γ of its receptor varies with epithelial differentiation and cell type

Normal keratinocytes from epidermis and from buccal mucosa were cultured to confluence in three media with graded differentiation potential and treated with interferon-gamma (IFN-gamma), RT-PCR was used to measure the gene expression of the IFN-gamma receptor (IFNGR-1), as well as the immunomodulator HLA-DR and two enzymes of the 2-5 A pathway. We have previously reported results for a number of structural and regulatory genes in the same system (and include here involucrin for comparison). In epidermal keratinocytes, the induction of IFNGR-1 was upregulated by incubation with IFN-gamma, and this increased with the differentiation potential of the culture medium. A roughly similar pattern occurred for the other genes. In mucosal keratinocytes, in contrast, IFN-gamma failed to induce expression of IFNGR-1 or the other genes, A unique characteristic of HLA-DR was that its induction by IFN-gamma was uniform, for both tissues and all media. The gene expression of the receptor IFNGR-1 appears to be the dominant factor in the sensitivity of other genes to IFN-gamma, although there are substantial disparities among them that presumably reflect functional differences. The difference between the two tissues may he linked to differentiation, as the epidermis has a much more extensive maturation pattern than the buccal mucosa, A clinical implication is a better prognosis for IFN-gamma treatment for more differentiated tumors. Indeed, a previous study has found that the maturation pattern of condylomas responding to interferon treatment resembles that of epidermis, whereas the maturation of nonresponders is more akin to that of buccal mucosa.