Sex-specific alterations in pulmonary metabolic, xenobiotic and lipid signalling pathways after e-cigarette aerosol exposure during adolescence in mice

IF 3.6 3区 医学 Q1 RESPIRATORY SYSTEM
Sofia Paoli, David H Eidelman, Koren K Mann, Carolyn Baglole
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引用次数: 0

Abstract

Background E-cigarette use is now prevalent among adolescents and young adults, raising concerns over potential adverse long-term health effects. Although it is hypothesised that e-cigarettes promote inflammation, studies have yielded conflicting evidence. Our previous work showed that JUUL, a popular e-cigarette brand, elicited minimal lung inflammation but induced significant molecular changes in adult C57BL/6 mice. Methods Now, we have profiled immunological and proteomic changes in the lungs of adolescent male and female BALB/c and C57BL/6 mice exposed to a flavoured JUUL aerosol containing 18 mg/mL of nicotine for 14 consecutive days. We evaluated changes in the immune composition by flow cytometry, gene expression levels by reverse transcription-quantitative PCR and assessed the proteomic profile of the lungs and bronchoalveolar lavage (BAL) by tandem mass tag-labelled mass spectroscopy. Results While there were few significant changes in the immune composition of the lungs, proteomic analysis revealed that JUUL exposure caused significant sex-dependent and strain-dependent differences in lung and BAL proteins that are implicated in metabolic pathways, including those related to lipids and atherosclerosis, as well as pathways related to immune function and response to xenobiotics. Notably, these changes were more pronounced in male mice. Conclusions These findings raise the possibility that vaping dysregulates numerous biological responses in lungs that may affect disease risk, disproportionally impacting males and raising significant concerns for the future health of male youth who currently vape. Data are available in a public, open access repository. Data are available on reasonable request. Proteomics data supporting the conclusions of this paper can be found at DOI: 10.6084/m9.figshare.26351740.
小鼠青春期接触电子烟气溶胶后肺部代谢、异生物和脂质信号通路的性别特异性改变
背景 目前,电子烟的使用在青少年和年轻成年人中十分普遍,这引起了人们对电子烟可能对健康造成的长期不利影响的担忧。尽管有假设称电子烟会促进炎症,但研究得出的证据却相互矛盾。我们之前的研究表明,JUUL(一种流行的电子烟品牌)在成年 C57BL/6 小鼠中引起的肺部炎症极小,但却诱发了显著的分子变化。现在,我们分析了连续 14 天暴露于含有 18 毫克/毫升尼古丁的 JUUL 气雾剂的雌雄 BALB/c 和 C57BL/6 青少年小鼠肺部的免疫学和蛋白质组变化。我们通过流式细胞术评估了免疫组成的变化,通过反转录定量 PCR 评估了基因表达水平,并通过串联质量标记质谱评估了肺和支气管肺泡灌洗液(BAL)的蛋白质组概况。结果 虽然肺部的免疫成分几乎没有发生明显变化,但蛋白质组分析表明,暴露于 JUUL 会导致肺部和 BAL 蛋白质出现明显的性别差异和菌株差异,这些蛋白质与代谢途径有关,包括与脂质和动脉粥样硬化有关的途径,以及与免疫功能和对异种生物反应有关的途径。值得注意的是,这些变化在雄性小鼠中更为明显。结论 这些研究结果表明,吸烟有可能导致肺部多种生物反应失调,从而影响疾病风险,对男性的影响尤为严重,并引发了人们对目前吸烟的男性青少年未来健康的极大担忧。数据可在公开、开放的资料库中获取。如有合理要求,可提供数据。支持本文结论的蛋白质组学数据见 DOI:10.6084/m9.figshare.26351740。
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
BMJ Open Respiratory Research
BMJ Open Respiratory Research RESPIRATORY SYSTEM-
CiteScore
6.60
自引率
2.40%
发文量
95
审稿时长
12 weeks
期刊介绍: BMJ Open Respiratory Research is a peer-reviewed, open access journal publishing respiratory and critical care medicine. It is the sister journal to Thorax and co-owned by the British Thoracic Society and BMJ. The journal focuses on robustness of methodology and scientific rigour with less emphasis on novelty or perceived impact. BMJ Open Respiratory Research operates a rapid review process, with continuous publication online, ensuring timely, up-to-date research is available worldwide. The journal publishes review articles and all research study types: Basic science including laboratory based experiments and animal models, Pilot studies or proof of concept, Observational studies, Study protocols, Registries, Clinical trials from phase I to multicentre randomised clinical trials, Systematic reviews and meta-analyses.
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