TNF-alpha and serum induce SKALP/elafin gene expression in human keratinocytes by a p38 MAP kinase-dependent pathway

Keratinocytes of inflamed epidermis (psoriasis, wound healing) are hyperpro liferative and display an abnormal differentiation programme. This regenera tive differentiation pathway is characterized by the induction of genes tha t are not expressed by keratinocytes in normal skin, such as the cytokerati ns CK6, CK16, CK17, and the proteinase inhibitor SKALP/elafin. In the study reported here we investigated the induction and regulation of SKALP expres sion as a marker for regenerative differentiation in epidermal keratinocyte s, Various cytokines and growth factors known to be present in psoriatic ep idermis were examined for their ability to induce SKALP gene expression in cultured human keratinocytes, Tumour necrosis factor-alpha (TNF-alpha) and serum were found to be potent inducers of SKALP expression at both the mRNA and the protein levels. SB202190 or SB203580, two specific p38 MAP kinase inhibitors almost completely blocked the induction of SKALP expression by T NF-alpha. and serum, These results suggest that in keratinocytes, p38 activ ity is crucial for the induction of SKALP gene expression, These findings c ould be relevant for the elucidation of the mechanisms involved in normal a nd disturbed epidermal differentiation.