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.