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在过敏性炎症中,单细胞和巨细胞的分子昼夜钟被破坏

Julia Teppan¹, Juliana Schwanzer¹, Sonja Rittchen^2,3

¹Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Frontiers in immunology

|June 12, 2024

概括

单细胞/巨细胞中循环时钟的干扰会损害喘患者的免疫功能. 用SR1001准时钟可以解决炎症并保护肺部,为慢性肺部疾病提供了一种新的治疗策略.

科学领域:

免疫学免疫学免疫学
时间生物学时间生物学
肺部病理学肺部病理学

背景情况:

巨细胞功能障碍是诸如喘之类的炎症性肺部疾病的核心.
喘表现出明显的昼夜节律,这表明与生物钟的联系.

研究的目的:

为了研究分子昼夜钟在人类单细胞和巨细胞中的蛋白质表达.
探索过敏性喘对免疫细胞中昼夜节律的影响.
为了评估时钟调节化合物的治疗潜力,SR1001.1.

主要方法:

从健康的,过敏的和喘的捐赠者中监测生物钟蛋白表达 (CLOCK,BMAL,REV ERBs,RORs) 在单细胞和衍生的巨细胞中.
分析了M1/M2极化巨细胞和精密切割的肺部切片中的蛋白质表达.
在体外评估SR1001对巨炎性蛋白质分泌和细胞分裂的影响.
在室内灰尘引发的喘模型中验证了SR1001的有效性.

主要成果:

在过敏性喘患者的单细胞中观察到振荡的昼夜蛋白质的显著变化.
在极化巨细胞和肺组织巨细胞中观察到BMAL1表达的类似变化.
SR1001表现出抗炎和肺部保护作用,减少炎症标志物和增强细胞化.
在喘模型中,SR1001在体内表现出治疗疗效.

结论:

在炎症性肺部疾病中,分子昼夜钟和单细胞/巨细胞功能之间存在显著的相互作用.
在体外和体内,SR1001促进炎症解消.
基于时钟的调制代表了对喘等慢性肺部疾病的有希望的治疗途径.

关键词:

在 REV ERB 激动剂 SR9009 的 SR9009 中.昼夜蛋白质是循环的蛋白质.这是一种炎症炎症炎症炎症.相反的ROR激动剂SR1001 一个反向的ROR激动剂SR1001.巨细胞是什么?巨细胞是什么?分子昼夜时钟是指分子昼夜时钟.

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