Protein kinase Cα (PKCα) is one of six PKC isoforms expressed in keratinocytes of mouse epidermis. To gain an understanding of the role of epidermal PKCα, we have localized its expression to specific cells of normal mouse skin and examined the effect of keratin 5 (K5) promoter directed expression of PKCα in transgenic mice. In normal mouse skin, PKCα was extensively expressed in the outer root sheath (ORS) keratinocytes of the anagen hair follicle and weakly expressed in keratinocytes of interfollicular epidermis. K5-targeted expression of PKCα to epidermal basal keratinocytes and follicular ORS keratinocytes resulted in a tenfold increase in epidermal PKCα. K5-PKCα mice exhibited no abnormalities in keratinocyte growth and differentiation in the epidermis. However, a single topical treatment with the PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a striking inflammatory response characterized by edema and extensive epidermal infiltration of neutrophils that formed intraepidermal microabscesses in the epidermis.

Compared to TPA-treated wild-type mice, the epidermis of TPA-treated K5-PKCα mice displayed increased expression of cyclooxygenase-2 (COX-2), the neutrophil chemotactic factor macrophage inflammatory protein-2 (MIP-2) mRNA and the proinflammatory cytokine TNFα mRNA but not IL-6 or IL-1α mRNA. To determine if K5-PKCα mice display an altered response to TPA-promotion, 7,12-dimethylbenz[a]anthracene-initiated K5-PKCα mice and wild-type mice were promoted with TPA. No differences in papilloma incidence or multiplicity were observed between K5-PKCα mice and wild-type littermates. These results demonstrate that the overexpression of PKCα in epidermis increases the expression of specific proinflammatory mediators and induces cutaneous inflammation but has little to no effect on epidermal differentiation, proliferation or TPA tumor promotion.