TNF-α and serum induce SKALP/elafin gene expression in human keratinocytes by a p38 MAP kinase-dependent pathway
TNF-α and serum induce SKALP/elafin gene expression in human keratinocytes by a p38 MAP kinase-dependent pathway
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DOI：
10.1007/s004030050475
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发表时间：
2000-04-01
影响因子：
3
通讯作者：
Schalkwijk, J
中科院分区：
文献类型：
--
作者：
Pfundt, R;Wingens, M;Schalkwijk, J
炎症表皮（牛皮癣、伤口愈合）的角化细胞增生，并表现出异常的分化程序。这种再生分化途径的特点是诱导正常皮肤中角质形成细胞不表达的基因，如细胞角蛋白CK6、CK16、CK17和蛋白酶抑制剂SKALP/elafin。在本文报道的研究中，我们研究了SKALP作为表皮角质形成细胞再生分化的标志的表达的诱导和调控，研究了银屑病表皮中存在的各种细胞因子和生长因子在培养的人角质形成细胞中诱导SKALP基因表达的能力，发现肿瘤坏死因子- α (tnf - α)和血清在mRNA和蛋白水平上都是SKALP表达的有效诱导剂。两种特异性p38 MAP激酶抑制剂SB202190或SB203580几乎完全阻断了tnf - α对SKALP表达的诱导。这些结果表明，在角质形成细胞中，p38活性对于诱导SKALP基因的表达至关重要，这些发现可能与阐明正常和异常表皮分化的机制有关。
Keratinocytes of inflamed epidermis (psoriasis, wound healing) are hyperproliferative and display an abnormal differentiation programme. This regenerative differentiation pathway is characterized by the induction of genes that are not expressed by keratinocytes in normal skin, such as the cytokeratins CK6, CK16, CK17, and the proteinase inhibitor SKALP/elafin. In the study reported here we investigated the induction and regulation of SKALP expression as a marker for regenerative differentiation in epidermal keratinocytes, Various cytokines and growth factors known to be present in psoriatic epidermis 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 TNF-alpha. and serum, These results suggest that in keratinocytes, p38 activity is crucial for the induction of SKALP gene expression, These findings could be relevant for the elucidation of the mechanisms involved in normal and disturbed epidermal differentiation.