The skin is the frontier of the immune system, the interface of the body with the external environment and the site of exposure of the immune system to muta-genic and oxidative damage from UV radiation (reviewed in Duthie ei al., 1999). Oxidizing agents are also produced by commensal microorganisms that reside on the skin. Se has been shown to have a vital role in protecting the skin from carcinogenesis and from oxidative damage (reviewed in McKenzie, 2000). In mice, dietary Se supplements or even topical application of Se significantly decrease the incidence of skin tumours, tumour size and mortality. Mice on Se-deficient diets also have significantly lower numbers of Langerhans cells in the skin, which may result from increased secretion of TNF-a, which triggers emigration of these dendritic cells. In humans, low Se intake has been correlated with increased incidence of skin cancer, but it is not clear yet whether Se supplements protect humans from skin damage and malignancy (reviewed in McKenzie, 2000).
In viiro, selenite and selenomethionine protect keratinocytes from UVB-induced cell death by necrosis and apoptosis. The mechanisms are thought to involve protection from lipid peroxidative damage to membranes, a decrease in oxidative DNA damage and inhibition of caspase-3, one of the proteases involved in triggering apoptosis (reviewed in McKenzie, 2000). For maximum protection, at least 12 h preincubation of the cells with the Se compounds is necessary, suggesting that the protection is mediated by selenoproteins. The GPX family seem to have an important role in this protection; for example, the molluscum contagiosum virus, which causes skin papules, carries an open reading frame encoding a GPX-like transcript. Transfection of this cDNA into keratinocytes protects them from UVB-induced cell death (Shisler ei al., 1998). Furthermore, unlike catalase, which also breaks down H2O2, GPX is not inactivated by UVB. Tanning of the skin protects against UVB, and thioredoxin reductase has been proposed to regulate the production of the melanin tanning pigment (reviewed in McKenzie, 2000). Thus, Se plays an important role in protecting the skin immune system from oxidative damage and carcinogenesis.
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