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

Autor: Manon C. Zweers, M. Frenken, Rolph Pfundt, J. Schalkwijk, M. Wingens, Mieke Bergers
Rok vydání: 2000
Předmět:
Keratinocytes
Pyridines
medicine.medical_treatment
p38 mitogen-activated protein kinases
Cellular differentiation
Blotting
Western
Proteinase Inhibitory Proteins
Secretory
The role of proteinases and proteinase inhibitors in epidermal differentiation and inflammation
Enzyme-Linked Immunosorbent Assay
Dermatology
Biology
p38 Mitogen-Activated Protein Kinases
Gene expression
medicine
Humans
RNA
Messenger
Enzyme Inhibitors
Cells
Cultured
Dose-Response Relationship
Drug
Epidermis (botany)
Tumor Necrosis Factor-alpha
Growth factor
De rol van proteasen en proteaseremmers bij epidermale differentiatie en ontstekingsprocessen
Imidazoles
Proteins
Cell Differentiation
General Medicine
Blotting
Northern
Fetal Blood
Cell biology
medicine.anatomical_structure
Gene Expression Regulation
Immunology
Mitogen-Activated Protein Kinases
Signal transduction
Keratinocyte
Elafin
Zdroj: Archives of Dermatological Research, 292, 180-7
Archives of Dermatological Research, 292, pp. 180-7
ISSN: 0340-3696
DOI: 10.1007/s004030050475
Popis: 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.
Databáze: OpenAIRE
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