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Transcriptional regulation of tumor necrosis factor‐α in keratinocytes mediated by interleukin‐1β and tumor necrosis factor‐α
Author(s) -
Lisby S.,
Hauser C.
Publication year - 2002
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1034/j.1600-0625.2002.110612.x
Subject(s) - tumor necrosis factor alpha , autocrine signalling , cytokine , interleukin , biology , cancer research , immunology , keratinocyte , proinflammatory cytokine , effector , microbiology and biotechnology , inflammation , receptor , cell culture , biochemistry , genetics
Irritant contact dermatitis (ICD) is an inflammatory skin reaction in which cytokines are thought to play a crucial role. In particular, tumor necrosis factor‐α (TNF‐α) has been implicated in the mechanism of this reaction. We report that interleukin‐1β (IL‐1β) that has been reported up‐regulated in many inflammatory skin conditions is capable of increasing TNF‐α mRNA and protein expression in murine keratinocytes. Furthermore, we show that TNF‐α is capable of up‐regulating itself in keratinocytes most likely in an autocrine manner. The signalling mechanisms involved in both IL‐1β‐ and TNF‐α‐mediated regulation of TNF‐α are critically dependent upon protein kinase C (PKC), as demonstrated by blocking studies using protein kinase inhibitors. Furthermore, the increase in TNF‐α mRNA expression seen after stimulation with rTNF‐α and rIL‐1β involved increased transcription of TNF‐α mRNA. This was demonstrated in a chloramphenicol acetyltransferase (CAT) assay using a CAT‐construct containing the full‐length TNF‐α promoter. These observations support the notion of keratinocytes functioning as an amplifier of pro‐inflammatory cytokine generation in the epidermis during ICD and other inflammatory skin conditions.