Tumour necrosis factor-alpha does not influence proliferation and differentiation of healthy and psoriatic keratinocytes in a skin-equivalent model

Abstract

Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of psoriasis. Its effect on keratinocytes from healthy and psoriatic skin was investigated. The keratinocytes were co-cultured with healthy and psoriatic fibroblasts in skin equivalents and grown in a serum-free medium for 15 days. TNF-alpha was added, or not, on day 12. The expression of differentiation and proliferation markers was investigated with immunohistochemistry. The epidermal growth rate was assessed by the percentage of Ki-67-positive nuclei in the basal layers of the outgrowths, which were all multilayered and orthokeratotic. The expression of the epidermal growth factor receptor, cytokeratin 16, involucrin and filaggrin displayed a hyperproliferative, regenerative pattern. No statistically significant differences in growth rate were found between the groups. These findings indicate a lack of effect of TNF-alpha on proliferation and differentiation in healthy and psoriatic keratinocytes. Further studies are warranted to elucidate the pathophysiological role of TNF-alpha in psoriasis.