UV LIGHT INDUCED EICOSANOID FORMATION AND METABOLISM

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Ultraviolet light (UVL) is a major contributor to human disease and cells of the skin its main target. The long term objectives of this project are to examine keratinocyte and melanocyte responses to acute UVL injury. Eicosanoids are released following UVL exposure to skin and could serve as mediators of post-UVL pigment production and melanocyte hyperplasia. These proposed studies will focus on the sources and likely role of eicosanoids on UVL produced pigmentation. Human keratinocytes will be examined as the initial target of UVL-induced injury. Following UVA, UVB, or PUVA irradiation of keratinocytes prelabelled with radioactive arachidonic acid, eicosanoids will be detected using HPLC, gas chromatography/mass spectroscopy, and/or immunoassays. To determine if eicosanoid metabolism following UVL is a multicell process, supernatants from UV-irradiated keratinocytes will be incubated with inflammatory cells. Detailed dose responses and time courses for each eicosanoid identified and each cell source will be determined. To corroborate the in vitro studies, human forearm skin will be irradiated in vivo, and suction blister fluid will be evaluated for the presence of individual eicosanoids identified in vitro. Each eicosanoid detected after UVL irradiation in vivo or in vitro will be examined for a dose-related effect on melanin production and melanocyte growth using human melanocyte cultures. Both short term and long term effects will be examined. Human melanocytes will also be examined for leukotriene receptors, for the ability to metabolize leukotrienes, and for leukotriene-induced migration. The ultimate goal of this work is to develop new information and treatment strategies for the sequelae of acute UVL exposure of the skin: sunburn, UVL-induced pigmentation and melanocyte hyperplasia and UVL-induced immunological suppression. Information obtained from this work will then be used to develop strategies to examine the sequelae of chronic ultraviolet light exposure of the skin.