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Induction of Manganese Superoxide Dismutase in Human Dermal Fibroblasts
A UV-BMediated Paracrine Mechanism With the Release of Epidermal Interleukin 1 , Interleukin 1 , and Tumor Necrosis Factor
Lale Naderi-Hachtroudi;
Thorsten Peters, MD;
Peter Brenneisen, PhD;
Christian Meewes, MD;
Christina Hommel;
Ziba Razi-Wolf, PhD;
Lars A. Schneider, MD;
Jutta Schüller, PhD;
Meinhard Wlaschek, PhD;
Karin Scharffetter-Kochanek, MD
Arch Dermatol. 2002;138:1473-1479.
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-Birradiated 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-Birradiated epidermal cells showed a marked increase in specific MnSOD messenger RNA and activity. Removal of interleukin 1 , interleukin 1 , and tumor necrosis factor 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.
From the Departments of Dermatology, University of Cologne, Cologne (Ms Naderi-Hachtroudi and Drs Peters, Meewes, Razi-Wolf, and Scharffetter-Kochanek), Dermatology and Allergology, University of Ulm, Ulm (Drs Peters, Schneider, Schüller, and Wlaschek and Ms Hommel), and Physiological Chemistry, University of Düsseldorf, Düsseldorf (Dr Brenneisen), Germany.
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