UV LIGHT INDUCED EICOSANOID FORMATION AND METABOLISM

紫外线(UVL)是导致人类疾病和细胞的主要因素 它的主要目标是皮肤。这个项目的长期目标是 检测角质形成细胞和黑素细胞对急性UVL损伤的反应。 二十烷类化合物在UVL暴露于皮肤后释放，可以作为 紫外线照射后色素产生和黑素细胞增殖的介体。这些 拟议的研究将集中于二十烷类化合物的来源和可能的作用。 UVL上产生色素沉着。 人角质形成细胞将被检测为UVL诱导的初始靶点 受伤。角质形成细胞经UVA、UVB或PUVA照射后 用放射性花生四烯酸预先标记，将检测到二十烷类化合物 使用高效液相色谱、气相色谱/质谱仪和/或免疫分析。 为了确定UVL后二十烷类代谢是否是一个多细胞过程， 紫外线照射的角质形成细胞的上清液将与 炎性细胞。每种药物的详细剂量反应和时间进程 鉴定了二十烷类化合物，并确定了每个细胞来源。 为了证实体外研究，人体前臂皮肤将受到辐射 在活体内，并将评估吸疱液中是否存在 体外鉴定的单个二十烷基类化合物。 在体内或体外UVL照射后检测到的每个二十烷类化合物都将是 检查对黑色素产生和黑素细胞的剂量相关影响 使用人类黑素细胞培养进行生长。无论是短期还是长期 我们将研究这些措施的效果。还将对人类黑素细胞进行检查 白三烯受体，用于代谢白三烯的能力，以及用于 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 急性UVL暴露皮肤后遗症的对策：晒伤， UVL诱导的色素沉着和黑素细胞增殖及UVL诱导 免疫抑制。从这项工作中获得的信息将在 被用来制定检查慢性精神分裂症后遗症的策略 皮肤暴露在紫外线下。

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.