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生长激素介导的巨噬细胞转录组和效应功能重编程。

Growth hormone-mediated reprogramming of macrophage transcriptome and effector functions.

机构信息

Faculdade de Nutrição, Universidade Federal de Pelotas, Pelotas, RS, Brazil.

College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, 32827, USA.

出版信息

Sci Rep. 2019 Dec 18;9(1):19348. doi: 10.1038/s41598-019-56017-6.

DOI:10.1038/s41598-019-56017-6
PMID:31852980
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6920138/
Abstract

Macrophages are an important component of the innate immune response. Priming and activation of macrophages is stimulated by cytokines (i.e IFNγ). However, growth hormone (GH) can also stimulate macrophage activation. Based on these observations, the goal of this work was to 1) to compare the transcriptome profile of macrophages activated in vitro with GH and IFNγ, and 2) to assess the impact of GH on key macrophage functional properties like reactive oxygen species (ROS) production and phagosomal proteolysis. To assess the global transcriptional and functional impact of GH on macrophage programming, bone marrow derived macrophages were treated with GH or IFNγ. Our data strongly support a potential link between GH, which wanes with age, and impaired macrophage function. The notable overlap of GH with IFNγ-induced pathways involved in innate immune sensing of pathogens and antimicrobial responses argue for an important role for GH in macrophage priming and maturation. By using functional assays that report on biochemical activities within the lumen of phagosomes, we have also shown that GH alters physiologically relevant processes such as ROS production and proteolysis. These changes could have far reaching impacts on antimicrobial capacity, signaling, and antigen presentation.

摘要

巨噬细胞是先天免疫反应的重要组成部分。细胞因子(如 IFNγ)刺激巨噬细胞的启动和激活。然而,生长激素(GH)也可以刺激巨噬细胞的激活。基于这些观察结果,这项工作的目标是 1)比较体外用 GH 和 IFNγ 激活的巨噬细胞的转录组谱,2)评估 GH 对关键巨噬细胞功能特性(如活性氧物质(ROS)产生和吞噬体蛋白水解)的影响。为了评估 GH 对巨噬细胞编程的全局转录和功能影响,用 GH 或 IFNγ 处理骨髓来源的巨噬细胞。我们的数据强烈支持 GH 与年龄相关的减弱和巨噬细胞功能受损之间存在潜在联系。GH 与参与病原体先天免疫感应和抗菌反应的 IFNγ 诱导途径的显著重叠表明 GH 在巨噬细胞的启动和成熟中起着重要作用。通过使用报告吞噬体内腔生化活性的功能测定,我们还表明 GH 改变了与生理相关的过程,如 ROS 产生和蛋白水解。这些变化可能对抗菌能力、信号转导和抗原呈递产生深远影响。

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