EICOSANOID FORMATION IN PULMONARY EPITHELIAL CELLS

肺上皮细胞中类二十烷酸的形成

• 批准号: 6290020
• 负责人: Thomas 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/6290020
• 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

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. We are currently investigating the regulation of 15-lipoxygenase expression and activity by several inflammatory cytokines. For example, IL4 increases the expression of 15-lipoxygenase in both squamous and mucociliary cells. However, only in the mucociliary cells was a very dramatic increase in 15-lipoxygenase-1 expression produced. IL-4 is reported to be an important inflammatory mediator in lung. We are now determining if 15-lipoxygenase metabolites influence the formation of mucus. The addition of IL-4 decreases the formation of mucus and the expression of several mucus related genes (Muc-5, Muc-5 a/c) suggesting that the expression of 15-lipoxygenase may down regulate of attenuate mucus formation. The human cells may be the best model to investigate the pulmonary inflammatory processes and the role of lipid mediators. However, additional experiments are required to determine if 15-LO modulates mucin secretion. These studies indicate an importance of 15- Lipoxygenase in human lung inflammatory responses. - 15-LO, COX-1,2, airway inflammation, mucin secretion, cell differentiation

气道上皮通过形成生物活性分子如类二十烷酸在肺的炎症作用中起重要作用。上皮作为气管和支气管的气液屏障，是包括粘蛋白在内的分泌物的来源。我们目前正在研究几种炎症细胞因子对15-脂氧合酶表达和活性的调节。例如，IL 4增加鳞状细胞和粘膜纤毛细胞中15-脂氧合酶的表达。然而，仅在粘液纤毛细胞中产生15-脂氧合酶-1表达的非常显著的增加。据报道IL-4是肺中重要的炎症介质。我们现在正在确定15-脂氧合酶代谢物是否影响粘液的形成。IL-4的添加减少了粘液的形成和几种粘液相关基因（Muc-5、Muc-5 a/c）的表达，这表明15-脂氧合酶的表达可能下调或减弱粘液的形成。人细胞可能是研究肺炎症过程和脂质介质作用的最佳模型。然而，需要额外的实验来确定15-LO是否调节粘蛋白分泌。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。- 考克斯-1，2，气道炎症，粘蛋白分泌，细胞分化