Transcriptomic analysis reveals distinct effects of cigarette smoke on murine airspace and bone-marrow derived macrophages.

IF 5.8 2区 医学 Q1 Medicine
Lynne Faherty, William Z Zhang, Mays M Salih, Elektra K Robinson, Elizabeth Perez, Kihwan Kim, Susan Carpenter, Suzanne M Cloonan
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引用次数: 0

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disease characterized by emphysema and chronic bronchitis and a leading cause of mortality worldwide. COPD is commonly associated with several comorbid diseases which contribute to exacerbated patient outcomes. Cigarette smoke (CS) is the most prominent risk factor for COPD development and progression and is known to be detrimental to numerous effector functions of lung resident immune cells, including phagocytosis and cytokine production. However, how CS mediates the various pathologies distant from the lung in COPD, and whether CS has a similar biological effect on systemic immune cells remains unknown.

Methods: C57BL/6 mice were exposed to 8 weeks of CS as an experimental model of COPD. Bone marrow cells were isolated from both CS-exposed and room air (RA) control mice and differentiated to bone marrow-derived macrophages (BMDMs). Airspace macrophages (AMs) were isolated from the same CS-exposed and RA mice and bulk RNA-Seq performed. The functional role of differentially expressed genes was assessed through gene ontology analyses. Ingenuity Pathway Analysis was used to determine the activation states of canonical pathways and upstream regulators enriched in differentially expressed genes in both cell types, and to compare the differences between the two cell types.

Results: CS induced transcriptomic changes in BMDMs, including an upregulation of genes in sirtuin signalling and oxidative phosphorylation pathways and a downregulation of genes involved in histone and lysine methylation. In contrast, CS induced decreased expression of genes involved in pathogen response, phagosome formation, and immune cell trafficking in AMs. Little overlap was observed in differentially expressed protein-coding genes in BMDMs compared to AMs and their associated pathways, highlighting the distinct effects of CS on immune cells in different compartments.

Conclusions: CS exposure can induce transcriptomic remodelling in BMDMs which is distinct to that of AMs. Our study highlights the ability of CS exposure to affect immune cell populations distal to the lung and warrants further investigation into the functional effects of these changes and the ensuing role in driving multimorbid disease.

转录组分析揭示了香烟烟雾对小鼠空腔和骨髓衍生巨噬细胞的不同影响。
背景:慢性阻塞性肺疾病(COPD)是一种以肺气肿和慢性支气管炎为特征的气道炎症性疾病,也是导致全球死亡的主要原因。慢性阻塞性肺病通常伴有多种并发症,这些并发症会加重患者的病情。香烟烟雾(CS)是导致慢性阻塞性肺病发展和恶化的最主要风险因素,众所周知,它对肺部常驻免疫细胞的多种效应功能(包括吞噬作用和细胞因子的产生)有害。然而,CS 是如何介导慢性阻塞性肺病中远离肺部的各种病变的,以及 CS 是否对全身免疫细胞具有类似的生物效应,这些仍然是未知数:方法:将C57BL/6小鼠作为慢性阻塞性肺病的实验模型,暴露于8周的CS。从暴露于 CS 的小鼠和室内空气(RA)对照组小鼠身上分离出骨髓细胞,并将其分化为骨髓源性巨噬细胞(BMDMs)。从相同的CS暴露小鼠和RA对照小鼠身上分离出空腔巨噬细胞(AMs),并进行了大量RNA-Seq分析。通过基因本体分析评估了差异表达基因的功能作用。使用 Ingenuity Pathway Analysis 确定两种细胞类型中富含差异表达基因的典型通路和上游调控因子的激活状态,并比较两种细胞类型之间的差异:结果:CS诱导了BMDMs的转录组变化,包括上调sirtuin信号通路和氧化磷酸化通路中的基因,以及下调参与组蛋白和赖氨酸甲基化的基因。与此相反,CS 会诱导 AMs 中涉及病原体反应、吞噬体形成和免疫细胞贩运的基因表达减少。与AMs相比,BMDMs中不同表达的蛋白编码基因及其相关通路几乎没有重叠,这突显了CS对不同区室中免疫细胞的不同影响:结论:CS 暴露可诱导 BMDMs 的转录组重塑,这一点与 AMs 不同。我们的研究凸显了暴露于 CS 会影响肺远端免疫细胞群的能力,因此有必要进一步研究这些变化的功能效应及其在多病驱动中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Respiratory Research
Respiratory Research RESPIRATORY SYSTEM-
CiteScore
9.70
自引率
1.70%
发文量
314
审稿时长
4-8 weeks
期刊介绍: Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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