Solar ultraviolet radiation (UV) is a ubiquitous environmental agent known to produce numerous effects in human skin including inflammation, pigmentation, alteration of immune function and carcinogenesis. The mechanism by which such radiation evokes most cutaneous photobiological responses remains poorly defined. Relatively little attention has been paid to the possible role of membrane constituents in the mediation of UV-induced skin changes. This is in spite of evidence from epidemiological, in vivo and in vitro studies which suggests that UV damage in skin results in stimulation of many biologic processes analogous to damage induced by membrane active agents. Such agents are known to act through alterations of membrane phospholipid structure and function including phospholipase activation, second messenger induction and lipid derived arachidonic acid metabolite production. The overall objective of these proposed studies is to examine the effect of UV on selected aspects of membrane phospholipid metabolism in human epidermis. Specifically, human epidermal keratinocytes will be utilized in culture as an in vitro model to assay the effect of UV (UVB -- 280-320 nm and UVA -- 320-400 nm) on phospholipase activation, arachidonate metabolite production, phosphatidylethanolamine methylation and the relationship of such membrane alterations to cellular proliferation and differentiation. Delineation of the effect of UV on membrane phospholipid metabolism of human keratinocytes should yield insight into the role played by such effects on the overall tissue response of human skin to sunlight.
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