INDUCTION BY INTERFERON-GAMMA OF ITS RECEPTOR VARIES WITH EPITHELIAL DIFFERENTIATION AND CELL-TYPE

Normal keratinocytes from epidermis and from buccal mucosa were cultur ed to confluence in three media with graded differentiation potential and treated with interferon-gamma (IFN-gamma), RT-PCR was used to meas ure the gene expression of the IFN-gamma receptor (IFNGR-1), as well a s the immunomodulator HLA-DR and two enzymes of the 2-5 A pathway. We have previously reported results for a number of structural and regula tory genes in the same system (and include here involucrin for compari son). In epidermal keratinocytes, the induction of IFNGR-1 was upregul ated by incubation with IFN-gamma, and this increased with the differe ntiation potential of the culture medium. A roughly similar pattern oc curred for the other genes. In mucosal keratinocytes, in contrast, IFN -gamma failed to induce expression of IFNGR-1 or the other genes, A un ique characteristic of HLA-DR was that its induction by IFN-gamma was uniform, for both tissues and all media. The gene expression of the re ceptor 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 differe nce between the two tissues may he linked to differentiation, as the e pidermis has a much more extensive maturation pattern than the buccal mucosa, A clinical implication is a better prognosis for IFN-gamma tre atment for more differentiated tumors. Indeed, a previous study has fo und that the maturation pattern of condylomas responding to interferon treatment resembles that of epidermis, whereas the maturation of nonr esponders is more akin to that of buccal mucosa.