KERATINOCYTES CONSTITUTIVELY EXPRESS THE FAS ANTIGEN THAT MEDIATES APOPTOSIS IN IFN-GAMMA-TREATED CULTURED KERATINOCYTES

The Fas antigen is a cell surface protein that can mediate apoptosis i n many cell types. Although its physiological function is still unclea r, recent evidence indicates that this surface molecule is involved in apoptosis in the immune system and the liver. The epidermis is an org an that undergoes terminal differentiation with the eventual death of keratinocytes, and it has been suggested that this is a specialized fo rm of apoptosis. In the present study, we examined whether or not the Fas antigen is involved in keratinocyte apoptosis. Immunoreactivity fo r the Fas antigen was found throughout the epidermis in normal human s hin sections and cultured normal human keratinocytes, and mRNA for the Fas antigen was found to be constitutively expressed in normal epider mis and cultured normal keratinocytes by RT-PCR analysis, To determine whether the Fas antigen in keratinocytes is functional, we used a cyt otoxic monoclonal antibody (mAb) against the Fas antigen to induce apo ptosis. This antibody did not induce apoptosis of cultured keratinocyt es even though they expressed the Fas antigen. We then tested the abil ity of several cytokines (TGF beta, TNF alpha and IFN gamma) to induce Fas-mediated keratinocyte apoptosis. Only pretreatment with IFN gamma followed by the addition of the anti-Fas mAb induced apoptosis, as as sessed by cell viability, morphological changes and ultrastructural ch aracteristics, suggesting that constitutive expression of the Fas anti gen is not sufficient to induce apoptosis in keratinocytes and that ke ratinocyte apoptosis via the Fas antigen-mediated mechanism may requir e the activation of keratinocytes by IFN gamma, which is thought to be produced by activated T cells. The Fas antigen may not be related to keratinocyte apoptosis that occurs in terminal differentiation, but ra ther to the apoptosis that occurs in inflammatory skin diseases.