CONTROL OF ARACHIDONIC ACID METABOLISM IN THYMIC EPITHELIAL CELLS

胸腺上皮细胞花生四烯酸代谢的控制

• 批准号: 3754386
• 负责人: JUN HAYASHI HAYASHI
• 金额: --
• 依托单位: ADIRONDACK BIOMEDICAL RESEARCH INSTITUTE
• 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/3754386
• 关键词: G protein; antibody; arachidonate; cytokine; epidermal growth factor; epithelium; fatty acid metabolism; high performance liquid chromatography; hormone regulation /control mechanism; in situ hybridization; laboratory mouse; laboratory rat; phospholipase A2; prostaglandin E; radioimmunoassay; systemic lupus erythematosus; thin layer chromatography; thymus; tissue /cell culture; transfection; tumor necrosis factor alpha

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.

花生四烯酸代谢产物在植物生长发育中起重要作用。 胸腺细胞的发育。 胸腺中的甘草素水平 比血浆浓度高4到10倍。结构性生产 维持胸腺中的前列腺素水平 对胸腺细胞的凋亡起重要作用， 选择过程。 胸腺上皮细胞负责 胸腺中产生的胸腺素。 根据我们最近的工作， 发现胸腺上皮细胞产生的胸腺素 细胞由PLA 2调节，PLA 2被TGF-α激活， 通过G蛋白介导的途径刺激的未鉴定配体。 在 本申请我们建议牢固地确立 EGF/TGF-α在调节花生四烯酸代谢中的作用 胸腺和鉴定刺激PLA 2活性的天然配体 通过G蛋白的激活。 我们还将阐明 花生四烯酸代谢的调控机制，并确定 参与系统性发展的有缺陷的要素 红斑狼疮（SLE）小鼠。 体外和体内研究均 提出使用正常和狼疮易感的NZB和NZB/W小鼠。 我们将 利用分子生物学和脂质生物化学来实现我们的目标 技术在实验中的应用。