{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:25:35Z","timestamp":1772781935913,"version":"3.50.1"},"reference-count":44,"publisher":"The Company of Biologists","issue":"20","license":[{"start":{"date-parts":[[1999,10,15]],"date-time":"1999-10-15T00:00:00Z","timestamp":939945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Protein kinase C\u03b1 (PKC\u03b1) is one of six PKC isoforms expressed in keratinocytes of mouse epidermis. To gain an understanding of the role of epidermal PKC\u03b1, we have localized its expression to specific cells of normal mouse skin and examined the effect of keratin 5 (K5) promoter directed expression of PKC\u03b1 in transgenic mice. In normal mouse skin, PKC\u03b1 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 PKC\u03b1 to epidermal basal keratinocytes and follicular ORS keratinocytes resulted in a tenfold increase in epidermal PKC\u03b1. K5-PKC\u03b1 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.<\/jats:p>\n               <jats:p>Compared to TPA-treated wild-type mice, the epidermis of TPA-treated K5-PKC\u03b1 mice displayed increased expression of cyclooxygenase-2 (COX-2), the neutrophil chemotactic factor macrophage inflammatory protein-2 (MIP-2) mRNA and the proinflammatory cytokine TNF\u03b1 mRNA but not IL-6 or IL-1\u03b1 mRNA. To determine if K5-PKC\u03b1 mice display an altered response to TPA-promotion, 7,12-dimethylbenz[a]anthracene-initiated K5-PKC\u03b1 mice and wild-type mice were promoted with TPA. No differences in papilloma incidence or multiplicity were observed between K5-PKC\u03b1 mice and wild-type littermates. These results demonstrate that the overexpression of PKC\u03b1 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.<\/jats:p>","DOI":"10.1242\/jcs.112.20.3497","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T17:22:16Z","timestamp":1619371336000},"page":"3497-3506","source":"Crossref","is-referenced-by-count":111,"title":["Overexpression of protein kinase C-\u03b1 in the epidermis of transgenic mice results in striking alterations in phorbol ester-induced inflammation and COX-2, MIP-2 and TNF-\u03b1 expression but not tumor promotion"],"prefix":"10.1242","volume":"112","author":[{"given":"Hui Qin","family":"Wang","sequence":"first","affiliation":[{"name":"Molecular and Cellular Toxicology, Department of Toxicology, North Carolina State University, Raleigh, NC 27695-7633, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Smart","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Toxicology, Department of Toxicology, North Carolina State University, Raleigh, NC 27695-7633, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1999,10,15]]},"reference":[{"key":"2024071016372271500_JOCES_112_20_3497C1","first-page":"4333","article-title":"Protein kinase activity associated with a phorbol ester receptor purified from mouse brain","volume":"43","author":"Ashendel","year":"1983","journal-title":"Cancer Res"},{"key":"2024071016372271500_JOCES_112_20_3497C2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0065-2776(08)60509-X","article-title":"Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines","volume":"55","author":"Baggiolini","year":"1994","journal-title":"Adv. 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