Interferon and the epidermis: implications for cellular senescence

Abstract

Human keratinocytes are epithelial cells that cover the external surface of the body and function primarily to protect against physical, chemical and biological injury. Since 1975, serial cultivation of disaggregated human keratinocytes in vitro has been possible and these cultures have been utilized to assess in vitro physiological age. As has been demonstrated in human dermal fibroblasts harvested from donors of different ages, human epidermal keratinocytes from older donors manifest a decreased proliferative response to serum and to selected mitogens when compared to younger donors. Recent work suggests an increased sensitivity to negative growth modulators as well. The epidermis constantly renews itself. In normal skin, the majority of the cells in the germinative, basal cell layer are blocked in Go and do not cycle unless stimulated. Interferons (IFN) are a family of glycoproteins well known for their antiviral activity and their ability to inhibit growth and alter the behavior of various normal and transformed cell types, both in vitro and in vivo. As such, we examined intact skin for the presence of negative modulators of growth and demonstrated the presence, by immunofluorescence and Western blotting, of a protein of approximate molecular weight 40 kilodaltons with polyclonal antiserum directed against recombinant IFN-alpha. Extracts from healthy, non-virally infected keratinocyte cultures contained IFN activity as determined by viral plaque inhibition assays. Further, we have demonstrated that IFN inhibits the growth of the human keratinocyte in a non-cytotoxic, reversible manner and that the keratinocytes harvested from older adult donors are significantly more sensitive to the growth inhibitory effects of IFN than are the keratinocytes of young donors.(ABSTRACT TRUNCATED AT 250 WORDS)