Induction of manganese superoxide dismutase in human dermal fibroblasts: a UV-B-mediated paracrine mechanism with the release of epidermal interleukin 1 alpha,interleukin 1 beta,and tumor necrosis factor alpha

BACKGROUND: Reactive oxygen species generated in the skin by UV irradiation promote photoaging and photocarcinogenesis. The manganese (Mn) superoxide dismutase (SOD) is a primary antioxidant enzyme that crucially contributes to the homeostasis of oxygen radicals within the mitochondria, and thus critically participates in the control of senescence and tumor generation. OBJECTIVE: To determine whether repetitive UV-B exposure, as practiced for light hardening during phototherapy for various photodermatoses, can enhance the adaptive antioxidant response by up-regulating MnSOD activity in either the epidermal or the dermal skin compartment. DESIGN: In vitro experiments to determine MnSOD activity levels in cultured human dermal fibroblasts and epidermal cells (HaCaT cells and primary keratinocytes) at different times after direct UV-B exposure or after incubation of human dermal fibroblasts with supernatants from UV-B-irradiated epidermal cells. SETTING: Photobiological research laboratory in a university dermatology department. INTERVENTION: Irradiation of cultured human dermal fibroblasts and epidermal cells with UV-B. MAIN OUTCOME MEASURES: Manganese SOD messenger RNA and activity levels in cultured irradiated or mock-treated skin cells. RESULTS: No increase in MnSOD activity could be detected in fibroblasts or epidermal cells until 24 hours after UV-B irradiation. However, fibroblasts incubated with supernatants from UV-B-irradiated epidermal cells showed a marked increase in specific MnSOD messenger RNA and activity. Removal of interleukin 1alpha, interleukin 1beta, and tumor necrosis factor alpha from the supernatants led to a significant reduction of MnSOD mRNA in fibroblasts. CONCLUSION: Irradiation of the epidermal cells with UV-B induced a release of soluble factors that amplified MnSOD activity in fibroblasts via a paracrine mechanism.