EICOSANOID FORMATION IN PULMONARY EPITHELIAL CELLS

气道上皮在炎症反应中起重要作用， 通过形成生物活性分子， 类花生酸 此外，上皮还充当气液屏障 是气管和支气管分泌物的来源，包括粘蛋白 它能捕捉粒子 类维生素A，它可以显着影响 呼吸道的分化状态对于维持 粘膜纤毛表型。 类维生素A的缺乏导致鳞状细胞癌 在几种肺部疾病中观察到的化生。 初始 该项目的目的是调查是否分化的 RTE细胞分为两种表型，受前列腺素和其他脂质影响 代谢产物的形成、PLA 2的表达和激活以及 表达前列腺素H合酶同种型和脂氧合酶。 随后的研究将侧重于了解 花生四烯酸代谢物的形成和调节 肺部反应。 两种表型的主要花生四烯酸代谢产物均为PGE 2。没有 检测到脂氧合酶代谢产物。分化的粘膜纤毛 细胞产生高水平的PGE 2，而分化的鳞状细胞 产生了非常低的水平。粘膜纤毛细胞表达高水平的 cPLA 2和PGHS-2 mRNA和蛋白。相比之下，鳞状细胞 检测cPLA 2和PGHS-2的表达。 PGHS-1亚型在 鳞状上皮细胞，而粘膜纤毛细胞则无。 虽然表达 cPLA 2和PGHS-2的表达依赖于粘膜-纤毛 在分化过程中，内源性PGE 2的形成仅受细胞增殖的限制。 表达cPLA 2。 其他数据支持的结论，表达 cPLA 2和PGHS-2的表达是分化的结果，而不是细胞增殖的结果。 视黄酸对这些酶的表达有直接影响。

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.