EICOSANOID FORMATION IN PULMONARY EPITHELIAL CELLS

肺上皮细胞中类二十烷酸的形成

• 批准号: 5202228
• 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/5202228
• 关键词: arachidonate; bronchial mucus; cell differentiation; eicosanoids; lipids; lipoxygenase; messenger RNA; phenotype; prostaglandins; protein isoforms; respiratory epithelium; retinoate; squamous cell carcinoma

The airway epithelium plays an important role in the inflammatory response of the lung by the formation of bioactive molecules such as eicosanoids. In addition the epithelium serves as an air-liquid barrier for the trachea and bronchi and is a source of secretions including mucin which traps particles. Retinoids, which can markedly influence the differentiation state of the airway are essential for maintaining the muco-cilliary phenotype. The absence of retinoids leads to squamous metaplasia which is observed in several lung diseases. The initial objective of this project was to investigate if differentiation of the RTE cells into the two phenotypes affected prostaglandin and other lipid metabolite formation, the expression and activation of PLA2 and the expression prostaglandin H synthase isoforms and lipoxygenases. Subsequent studies will focus on developing an understanding the between formation of arachidonic acid metabolites and modulation or regulation of pulmonary responses. The major arachidonic acid metabolite was PGE2 for both phenotypes. No lipoxygenase metabolites were detected. Differentiated muco-cilliary cells produced high levels of PGE2 whereas differentiated squamous cells produced very low levels. Muco-cilliary cells expressed high levels of cPLA2 and PGHS-2 mRNA and protein. In contrast, squamous cells low levels of cPLA2 and PGHS-2 were detected. The PGHS-1 isoform was observed in the squamous but not in the muco-cilliary cells. Although the expression of cPLA2 and PGHS-2 expression was dependent on muco-cilliary differentiation, the formation of endogenous PGE2 was limited only by the expression cPLA2. Other data support the conclusion that the expression of cPLA2 and PGHS-2 is the result of differentiation and not the result of a direct effect of retinoic acid on the expression of these enzyme.

呼吸道上皮细胞在炎症反应中起重要作用 肺通过形成生物活性分子，如 二十烷类化合物。此外，上皮细胞还起到了气液屏障的作用。 用于气管和支气管，是包括粘液在内的分泌物的来源 它可以捕获粒子。维甲酸，它可以显著影响 气道的分化状态对于维持 粘液纤毛表型。缺乏维甲酸会导致鳞状细胞癌 在几种肺部疾病中观察到的化生。首字母 该项目的目标是调查是否存在分化的 RTE细胞转化成两种表型影响前列腺素等脂质 代谢产物的形成、磷脂酶A2的表达和激活以及 前列腺素H合成酶亚型和脂氧合酶的表达。 后续的研究将集中于发展对 花生四烯酸代谢产物的形成及其调控 肺部反应。 两种表型的花生四烯酸代谢产物均为PGE2。不是 检测脂氧合酶代谢产物。分化粘液纤毛 细胞产生高水平的PGE2，而分化的鳞状细胞 产生了非常低的水平。粘液纤毛细胞高水平表达 CPLA2和PGHS-2mRNA和蛋白的表达。相比之下，鳞状细胞的水平较低 检测cPLA2和PGHS-2的表达。观察到PGHS-1亚型在 鳞状细胞，但不在粘液纤毛细胞中。尽管该表达式 CPLA2和PGHS-2的表达依赖于粘液纤毛 分化过程中，内源性PGE2的形成仅受 表达cPLA2。其他数据支持这一结论，即 CPLA2和PGHS-2的表达是分化的结果，而不是 维甲酸对这些酶的表达有直接影响。