EICOSANOID FORMATION IN PULMONARY EPITHELIAL CELLS

肺上皮细胞中类二十烷酸的形成

• 批准号: 6162252
• 负责人: T ELING
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162252
• 关键词: arachidonate; bronchial mucus; cell differentiation; eicosanoid metabolism; eicosanoids; fatty acid biosynthesis; gene expression; human genetic material tag; human tissue; inflammation; laboratory rat; lipoxygenase; messenger RNA; phenotype; phospholipase A2; prostaglandin E; protein isoforms; respiratory epithelium; retinoate; tissue /cell culture

Summary of Work: The airway epithelium plays an important role in the inflammatory role of the lung by the formation of bioactive molecules such as eicosanoids. The epithelium serves as an air-liquid barrier for the trachea and bronchi and is a source of secretions including mucin. Retinoids are essential for maintaining the muco-cilliary phenotype. The absence of retinoids leads to squamous metaplasia which is observed in several lung diseases. The major arachidonic acid metabolite was PGE2 for both squamous and muco-cilliary rat phenotypes. Muco-cilliary cells produced high levels of PGE2, express high levels of cPLA2 and PGHS-2, whereas squamous cells produced very low levels of PGHS-2. The PGHS-1 isoform was observed in the squamous but not in the muco-cilliary cells. Recently, the air-liquid interface system used to investigate differentiation of rat tracheal cells into squamous and muco-cilliary phenotype has been successfully extended to human bronchial epithelial cells. The human cells poorly metabolize arachidonic acid to prostaglandins in contrast to the rat cells. In the absence of retinoids, 15-lipoxygenase and PGHS-2 was not detected. With retinoids, these cells differentiate to mucocilliary cells and Western and Northern analysis indicated the presence of high levels of the 15-lipoxygenase. Although arachidonic acid is poorly metabolized by intact cells, linoleic acid is converted extensively to 13(S)-HODE. However, 15-lipoxygenase can metabolize arachidonic acid in cell lysates. These studies indicate an importance of 15-lipoxygenase in human lung inflammatory responses.

工作总结：气道上皮细胞在呼吸道疾病中起着重要作用。 通过生物活性分子的形成对肺的炎症作用 例如类二十烷酸。 上皮细胞作为空气-液体屏障， 气管和支气管，并且是包括粘蛋白的分泌物的来源。 类维生素A是维持粘膜纤毛表型所必需的。 的 类维生素A缺乏导致鳞状上皮化生， 几种肺部疾病 花生四烯酸的主要代谢产物为PGE 2 鳞状和粘膜纤毛大鼠表型。 粘膜纤毛细胞 产生高水平的PGE 2，表达高水平的cPLA 2和PGHS-2， 而鳞状细胞产生的PGHS-2水平非常低。 PGHS-1 在鳞状细胞中观察到同种型，但在粘膜纤毛细胞中未观察到同种型。 近年来，空气-液体界面系统用于研究 大鼠气管细胞向鳞状和粘膜纤毛细胞的分化 表型已成功地扩展到人支气管上皮细胞 细胞 人体细胞很少代谢花生四烯酸， 与大鼠细胞相比， 在没有 未检测到类维生素A、15-脂氧合酶和PGHS-2。 对于类维生素A， 这些细胞分化为粘液纤毛细胞和Western和北方 分析表明存在高水平的15-脂氧合酶。 虽然花生四烯酸被完整细胞代谢不良， 酸大量转化为13（S）-HODE。 然而，15-脂氧合酶 可以代谢细胞裂解物中的花生四烯酸。 这些研究表明 15-脂氧合酶在人类肺部炎症反应中的重要性。