Role of prolyl-hydroxylase domain enzyme inhibitors in chronic renal inflammation (B05)

脯氨酰羟化酶结构域酶抑制剂在慢性肾脏炎症中的作用 (B05)

• 批准号: 415853519
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/415853519?language=en
• 关键词: Role; prolyl; hydroxylase; domain; enzyme

Inhibition of prolyl hydroxylase domain enzymes (PHDi) protects mice in a model of chronic tubulointerstitial inflammasome-dependent kidney disease. PHDi-mediated protection required the presence of mononuclear phagocytes. Moreover, PHDi blocked caspase-1-dependent IL-1β release in mononuclear phagocytes. In order to test whether PHDi in mononuclear phagocytes ameliorates chronic nephritis we will characterize and analyze the contribution of subsets of mononuclear phagocytes in the pathogenesis of chronic inflammatory kidney diseases and their role in PHDi-mediated protection. Moreover, we will decipher how PHDi-treatment impairs IL-1β release in mononuclear phagocytes.

抑制脯氨酰羟化酶结构域酶（PHDi）可保护慢性肾小管间质炎性小体依赖性肾病模型小鼠。PHDi介导的保护需要单核吞噬细胞的存在。此外，PHDi阻断了单核吞噬细胞中caspase-1依赖性IL-1β的释放。为了测试单核吞噬细胞中的PHDi是否改善慢性肾炎，我们将表征和分析单核吞噬细胞亚群在慢性炎症性肾病发病机制中的贡献及其在PHDi介导的保护中的作用。此外，我们将解释PHDi处理如何损害单核吞噬细胞中IL-1β的释放。