Epidermal COX-2 Induction Following Ultraviolet Irradiation: Suggested Mechanism for the Role of COX-2 Inhibition in Photoprotection
| Autor: | Medora M. Hardy, Kevin S. Chinn, Alice P. Pentland, Peter LaCelle, Catherine S. Tripp, Eric A.G. Blomme |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Keratinocytes
Skin Neoplasms Ultraviolet Rays Prostaglandin Dermatology Biology Skin Diseases Biochemistry Malignant transformation Mice chemistry.chemical_compound medicine Animals Cyclooxygenase Inhibitors Prostaglandin E2 Molecular Biology Mice Hairless Cyclooxygenase 2 Inhibitors integumentary system Epidermis (botany) Cell Biology Hairless Isoenzymes medicine.anatomical_structure Epidermal Cells chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Apoptosis Acute Disease Cancer research biology.protein Female Cyclooxygenase Epidermis Keratinocyte Cell Division medicine.drug |
| Zdroj: | Journal of Investigative Dermatology. 121:853-861 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2003.12495.x |
| Popis: | The cyclooxygenase isoforms, COX-1 and COX-2, are involved in the biosynthesis of prostaglandin E2, a major prostaglandin involved in epidermal homeostasis and repair. Cancer originating in the epidermis can develop when keratinocyte proliferation and apoptosis become dysregulated, resulting in sustained epidermal hyperplasia. COX-2 inhibitors, which demonstrate significant in vivo selectivity relative to COX-1, suppress both ultraviolet-induced epidermal tumor development and progression, suggesting that prostaglandin regulation of keratinocyte biology is involved in the pathogenesis of epidermal neoplasia. In this study, we characterized the expression of COX-1 and COX-2, as well as keratinocyte proliferation, differentiation, and apoptosis, following acute ultraviolet irradiation in the hairless SKH-1 mouse. Following acute ultraviolet exposure, COX-2 expression was predominantly induced in the basal keratinocyte layer coincident with an increase in keratinocyte proliferation and apoptosis. The role of COX-2 was further evaluated using a selective COX-2 inhibitor, SC-791, as well as the traditional nonsteroidal COX inhibitor, indomethacin. Following acute ultraviolet irradiation, inhibition of COX-2 with either inhibitor decreased epidermal keratinocyte proliferation. Likewise, keratinocyte apoptosis was increased with COX-2 inhibition, particularly in the proliferating basal keratinocyte layer. There was also a modest inhibition of keratinocyte differentiation. These data suggest that COX-2 expression is probably necessary for kera-tinocyte survival and proliferation occurring after acute ultraviolet irradiation. We hypothesize that selective COX-2 inhibition, as described herein, may lead to enhanced removal of ultraviolet-damaged keratinocytes, thereby decreasing malignant transformation in the epidermis. |
| Databáze: | OpenAIRE |
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