CONTROL OF ARACHIDONIC ACID METABOLISM IN THYMIC EPITHELIAL CELLS

花生四烯酸的代谢物在 胸腺细胞的发育。胸腺中的前列腺素水平是 比血浆水平高4到10倍。本质性生产 而维持胸腺中的前列腺素水平可能是 对阴性所致胸腺细胞的凋亡有重要作用 选拔过程。胸腺上皮细胞负责 在胸腺中产生前列腺素。从我们最近的工作来看，我们有 发现胸腺上皮细胞产生前列腺素 细胞受磷脂酶A2的调节，磷脂酶A2由转化生长因子-α激活，但 通过G蛋白介导的途径刺激的未知配体。在……里面 我们提出的这一应用程序牢固地确立了 表皮生长因子/转化生长因子-α在花生四烯酸代谢调节中的作用 并确定刺激PLA2活性的天然配体 通过激活G蛋白。我们还将阐明总体情况 花生四烯酸代谢的调节机制及鉴定 参与系统性发展的缺陷元素(S) 小鼠红斑狼疮(SLE)。体外和体内研究都是 建议使用正常和易患狼疮的NZB和NZB/W小鼠。我们会 用分子生物学和脂类生化来实现我们的目标 拟议实验中的技术。

The arachidonic acid metabolites play an important role in the development of thymocytes. The levels of prostaglandins in the thymus is 4 to 10 times higher than the plasma levels. The constitutive production and the maintenance of prostaglandin levels in the thymus is probably important for the apoptosis of thymocytes resulting from the negative selection processes. The thymic epithelial cells are responsible for the production of prostagladins in the thymus. From our recent work, we have found that the production of prostaglandins by the thymic epithelial cells is regulated by PLA2 which is activated by both TGF-alpha and yet unidentified ligand that stimulates via G protein mediated pathway. In this application we propose to firmly establish the physiological role of EGF/TGF-alpha in the regulation of arachidonic acid metabolism in the thymus and identify the natural ligand that stimulate PLA2 activity through the activation of G protein. We will also elucidate the overall regulatory mechanism of arachidonic acid metabolism and identify the defective element(s) that is involved in the development of systemic lupus erythematosus (SLE) in mice. Both in vitro and in vivo studies are proposed using normal and lupus prone NZB and NZB/W mice. We will achieve our goal using both molecular biological and lipid biochemical techniques in proposed experiments.