Ultraviolet B (UVB)-induced COX-2 expression in murine skin: An immunohistochemical study

Cyclooxygenase (COX) is the rate-limiting enzyme in the production of prost aglandins from arachidonic acid. This enzyme exists in at least two isoform s, COX-1 and COX-2. COX-1 is constitutively expressed in most tissues and p lays various physiological roles. However, COX-2 expression is induced by a variety of agents, which include pro-inflammatory agents and mitogens. Evi dence exists to indicate that increased expression of COX-2 occurs in sever al types of epithelial neoplasms. In this study, we show the effect of chro nic exposure of murine skin to carcinogenic UVB on cutaneous COX-2 expressi on. SKH-1 mice were irradiated with 180 mJ/cm(2) UVB daily for five days a week for periods ranging from 1 to 20 weeks. Nontumor bearing skin areas of irradiated mice, skin of age-matched controls and benign papillomas and ma lignant tumors were assessed immunohistochemically a for COX-2 expression i n these mice. No epidermal staining occurred in any of the non-UVB-treated controls throughout the experiment. Epidermal COX-2 expression only occurre d in UVB-irradiated mice. After 1 and 5 weeks of irradiation, patchy epider mal staining mostly confined to the granular layer and stratum corneum was observed. At week 9, staining intensity had increased, particularly in the granular layer. At week 13, staining was uniformly seen in all epidermal la yers with particular prominence in the basal cell layer underlying areas of visible epidermal hyperplasia. It is of interest that the most intense sta ining was seen in the perinuclear region of keratinocytes and at the plasma membrane. At week 20, COX-2 staining was predominant in the granular layer , although in some tissue sections, the entire epidermis was positive. In b enign papillomas, staining was confined to the superficial layers of the ep idermis and in squamous cell carcinomas (SCCs), patchy staining in the gran ular and spinous layers predominated. In general, COX-2 expression was more intense in well-differentiated SCCs than in papillomas. In summary, our re sults indicate that COX-2 serves as an early marker of epidermal UVB exposu re and its expression increases in benign papillomas and in SCCs, These res ults suggest that pharmacological intervention using specific COX-2 inhibit ors could have anticarcinogenic effects in UVB-induced human shin cancer. ( C) 2001 Academic Press.