Journal Article

Epidermal COX-2 Induction Following Ultraviolet Irradiation: Suggested Mechanism for the Role of COX-2 Inhibition in Photoprotection

LaCelle, Peter, Tripp, Catherine S., Blomme, Eric A.G., Hardy, Medora M., Chinn, Kevin S., Pentland, Alice P.

2003

Overview

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.

• Publisher: Elsevier Inc,Nature Publishing
• Subject: Acute Disease / Animals / Biological and medical sciences / Biological effects of radiation / Cell Division - physiology / Cell Division - radiation effects / Cyclooxygenase 2 / Cyclooxygenase 2 Inhibitors / Cyclooxygenase Inhibitors - pharmacology / epidermis / Epidermis - cytology / Epidermis - enzymology / Epidermis - radiation effects / Female / Fundamental and applied biological sciences. Psychology / Isoenzymes - antagonists & inhibitors / Isoenzymes - metabolism / keratinocyte / Keratinocytes - cytology / Keratinocytes - enzymology / Keratinocytes - radiation effects / Mice / Mice, Hairless / Non ionizing radiations. Hertzian waves. Biooptics / Prostaglandin-Endoperoxide Synthases - metabolism / Skin Diseases - drug therapy / Skin Diseases - metabolism / Skin Neoplasms - metabolism / Skin Neoplasms - prevention & control / Tissues, organs and organisms biophysics / ultraviolet / Ultraviolet Rays - adverse effects