THE EFFECT OF IFN-GAMMA ON HEALTHY AND PSORIATIC KERATINOCYTES IN A SKIN EQUIVALENT MODEL IS INFLUENCED BY THE SOURCE OF THE KERATINOCYTES AND BY THEIR INTERACTIONS WITH FIBROBLASTS

We investigated the effect of interferon-gamma (IFN-gamma) on skin equ ivalents, Keratinocytes from involved and uninvolved skin from psoriat ic subjects and from healthy subjects were grown on preproduced dermal equivalents (DE) containing fibroblasts from healthy skin or psoriati c lesions, Healthy keratinocytes were added when the dermal equivalent s were either 22 days (DE(22)) or 37 days old (DE(37)) and psoriatic k eratinocytes when the dermal equivalents were 28-52 days old (DE(28-52 )), The skin equivalents were cultured for 11 days in a serum-free med ium, and then with or without 500 U/ml IFN-gamma for 6 days, The expre ssion of markers associated with differentiation and proliferation wer e investigated by immunohistochemistry, Differentiation was assessed b y computed scores for the expression of cytokeratin 16, involucrin, fi laggrin and the receptor for epidermal growth factor, The differentiat ing effect of IFN-gamma on healthy keratinocytes grown on DE(37) was s ignificantly stronger than on psoriatic keratinocytes grown on DE(28-5 2), In healthy keratinocytes, the differentiating effect of IFN-gamma was significantly stronger in skin equivalents containing DE(37) than in those containing DE(22), The proliferation rate, i,e, the percentag e of Ki-67(+) keratinocytes in the basal layer, was studied in healthy keratinocytes grown on DE(22), In these cultures IFN-gamma increased the proliferation rate in the presence of psoriatic fibroblasts but no t in the presence of healthy fibroblasts, HLA-DR expression was induce d only in healthy keratinocytes grown on DE(22), We conclude that the influence of IFN-gamma on epidermal differentiation and proliferation is influenced by the origins of both the keratinocytes and the fibrobl asts. These findings suggest that interactions between keratinocytes a nd fibroblasts might be involved in the pathogenesis of psoriasis.