The expression of the various markers for terminal epidermal differentiation in atrophic skin of patients after long-term topical corticosteroids (TCS) was studied by electron microscopy, immunofluorescence using antibody to profilaggrin/filaggrin (PF/FG), immunoperoxidase staining using antibody to involucrin, and oil red O stain for neural lipids of the stratum corneum. Thirty-nine patients were subdivided into two groups: (A) 19 patients suffering from rebound phenomenon after stopping TCS and (B) 20 patients without rebound phenomenon. Biopsy specimens were taken before ending the use of TCS in both groups. In group A, both the morphological markers (including the different epidermal strata, keratohyalin granules, lamellar granules, and cornified cell envelopes) and the molecular markers (including involucrin, PF/FG, and neutral lipids) of terminal epidermal differentiation were significantly suppressed. On the other hand, the differentiational markers in the atrophic skin of patients without rebound phenomena were only slightly altered. These results suggest that potent TCS not only has antiproliferative actions but also inhibits the differentiation of epidermis, resulting in structural defects in the epidermis, especially the stratum corneum.
Cyclooxygenase (COX)-2 inhibitors are known to be used as chemopreventative agents against certain malignancies. Thus far, there has been very limited information on whether COX-2 inhibitors protect against chronic narrow-band UVB (NB-UVB)-induced immunosuppression. The present study investigated the effect of nonselective and specific COX-2 inhibitors, indomethacin and celecoxib, on epidermal Ia+ Langerhans cells (LCs) and Thy-1+ dendritic epidermal T cells (DETCs) in mice irradiated with NB-UVB. Sixty female BALB/c mice were divided randomly into the control group (sham) and the experimental groups (irradiated with NB-UVB for 17 weeks, further divided into five groups according to the diets containing different concentrations of either COX-2 inhibitors). Alterations in the density and morphology of epidermal Ia+ LCs and Thy-1+ DETCs in mice were documented using fluorescence microscopy. Chronic NB-UVB irradiation substantially decreased the density and altered the morphology of the epidermal Ia+ LCs and Thy-1+ DETCs in control mice. The dietary supplementation of both COX-2 inhibitors displayed a dosage-dependent protective effect on the murine dendritic cells irradiated by NB-UVB. In conclusion, COX-2 inhibitors protected against chronic NB-UVB-induced density and morphologic changes in epidermal Ia+ LCs and Thy-1+ DETCs in mice.
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