Dermatotoxic chemical stimulate of c-jun and c-fos transcription and AP-1 DNA binding in human keratinocytes.
In many organ/tissues rapid and transient increases in early-immediate gene responses, such as those that encode for the AP-1 family of transcription factors, occur in response to exogenous stimuli. Activation of AP-1, in turn, helps regulate the expression of genes involved in cell growth, inflammatory responses, and repair processes. In the present studies, we demonstrate that increases in AP-1 DNA binding activity, as well as c-jun and c-fos mRNA levels, occur in human keratinocytes in response to diverse dermatotoxic chemicals, including phenol and arsenic as well as phorbol ester, the latter employed as a positive control. The AP-1 DNA binding complex has affinity for the consensus AP-1 sequence but not the CRE2 binding sequence of the proenkephalin promoter or the NF kappa B consensus sequence indicating that the response is relatively specific. The binding complex is composed of Jun:Fos heterodimers, including Jun B and Jun D. Evidence is provided suggesting that AP-1 binding is associated with an increase in IL-1 alpha expression, an early mediator of toxic response in the skin.
Burleson
F G
FG
Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA.
Simeonova
P P
PP
Germolec
D R
DR
Luster
M I
MI
D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
D007375:Interleukin-1; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D004247:DNA