Characterization of Macroph-aging: the Role of GILZ (Glucocortioid-Induced Leucin Zipper)

巨噬细胞衰老的表征：GILZ（糖皮质激素诱导的亮氨酸拉链）的作用

• 批准号: 163639620
• 负责人: Professorin Dr. Alexandra K. Kiemer
• 金额: --
• 依托单位: Institut für Pharmazeutische Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/163639620?language=en
• 关键词: Characterization; Macroph; aging; Role; GILZ

Aging is characterized by chronic inflammatory processes. Macrophages as innate immune cells distinctly contribute to this permanent inflammation. Our own data show that the protein GILZ (glucocorticoid-induced leucine zipper) regulates the activation of mouse macrophages obtained from young mice: an acute decrease in GILZ levels amplifies the defense readiness of macrophages. On the other hand, increasing GILZ levels contribute to the resolution of inflammation and to the re-establishment of a resting state.In immune cells from aged animals we observed decreased GILZ levels, which go along with an elevated immune response. At the same time we could show that inflammatory processes as well as the presence or absence of macrophages induce epigenetic changes in these tissues. Epigenetic changes have increasingly been recognized as important characteristics of aging processes.Based on this knowledge the following hypotheses will be tested within this project:(I) Chronic age-dependent inflammatory reactions are based on reduced GILZ levels. Attenuated GILZ impairs the resolution of inflammation, which are normally due to tolerization phenomena.(II) The age-dependent decrease of GILZ levels is induced by an altered glucocorticoid metabolism.(III) Macrophages themselves show signs of senescence and promote aging phenomena in the tissues, in which they reside. The hypotheses will be tested in tissue cultures, in mouse in vivo investigations, as well as in experiments on human lung macrophages. For the first time this project aims to decipher the epigenetic aging of macrophages from mice and humans via next generation sequencing techniques.The project will deliver fundamental knowledge on aging phenoma in macrophages and how these contribute to aging processes of the whole organism.

衰老的特点是慢性炎症过程。巨噬细胞作为先天免疫细胞，明显导致这种永久性炎症。我们自己的数据表明，蛋白质 GILZ（糖皮质激素诱导的亮氨酸拉链）可调节从幼鼠获得的小鼠巨噬细胞的激活：GILZ 水平的急剧下降会增强巨噬细胞的防御准备状态。另一方面，增加 GILZ 水平有助于炎症的消退和重新建立静息状态。在老年动​​物的免疫细胞中，我们观察到 GILZ 水平降低，这伴随着免疫反应的升高。同时我们可以证明炎症过程以及巨噬细胞的存在或不存在会诱导这些组织的表观遗传变化。表观遗传变化越来越被认为是衰老过程的重要特征。基于这些知识，本项目将测试以下假设：（I）慢性年龄依赖性炎症反应基于 GILZ 水平降低。减弱的 GILZ 会损害炎症的消退，这通常是由于耐受现象造成的。(II) GILZ 水平的年龄依赖性下降是由糖皮质激素代谢改变引起的。(III) 巨噬细胞本身表现出衰老迹象，并促进其所在组织的衰老现象。这些假设将在组织培养、小鼠体内研究以及人肺巨噬细胞实验中进行测试。该项目首次旨在通过下一代测序技术破译小鼠和人类巨噬细胞的表观遗传衰老。该项目将提供有关巨噬细胞衰老现象以及它们如何影响整个生物体衰老过程的基础知识。