UV LIGHT INDUCED EICOSANOID FORMATION AND METABOLISM

紫外线（UVL）是人类疾病和细胞的主要贡献者 皮肤是它的主要目标。 该项目的长期目标是 检测角质形成细胞和黑素细胞对急性UVL损伤的反应。 类二十烷酸在紫外线暴露于皮肤后释放，可用作 UVL后色素产生和黑素细胞增生的介质。 这些 拟议的研究将集中在类花生酸的来源和可能的作用， 产生色素沉着。 将检查人角质形成细胞作为UV诱导的细胞凋亡的初始靶标。 损伤 在UVA、UVB或PUVA照射角质形成细胞后 用放射性花生四烯酸预标记， 使用HPLC、气相色谱/质谱和/或免疫测定。 为了确定UVL后类花生酸代谢是否是一个多细胞过程， 将来自UV照射的角质形成细胞的上清液与 炎症细胞 每种药物的详细剂量反应和时间过程 鉴定类二十烷酸并确定每种细胞来源。 为了证实体外研究，将对人前臂皮肤进行辐照 在体内，将评价抽吸水疱液中是否存在 体外鉴定的单个类二十烷酸。 在体内或体外UVL照射后检测到的每种类二十烷酸将是 检查对黑色素生成和黑素细胞的剂量相关效应 使用人黑素细胞培养物的生长。 短期和长期 将检查效果。 人类黑素细胞也将被检查， 白三烯受体，代谢白三烯的能力，以及 白三烯诱导的迁移。 这项工作的最终目标是开发新的信息和治疗方法 用于皮肤急性UVL暴露后遗症的策略：晒伤， 紫外线诱导的色素沉着和黑素细胞增生以及紫外线诱导的 免疫抑制 从这项工作中获得的信息将 用于制定战略，以检查慢性 皮肤的紫外线照射。

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.