Arunava Ghosh, Keith L Rogers, Samuel C Gallant, Yong Ho Kim, Julia E Rager, M Ian Gilmour, Scott H Randell, Ilona Jaspers
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Cellular gene expression was analyzed using bulk RNA sequencing, and basolateral media cytokine levels were assessed using multiplex immunoassay.</p><p><strong>Results: </strong>Flaming smoke condensates caused more significant differentially expressed genes (DEGs) with plywood flaming smoke being the most potent in altering gene expression and modulating cytokine release. Cardboard and plywood flaming condensates primarily activated detoxification pathways, whereas plastic flaming affected genes related to anti-microbial and inflammatory responses. Correlation analysis between smoke condensate chemicals and gene expression to understand the underlying mechanism revealed crucial role of oxygenated polycyclic aromatic hydrocarbons (PAHs) and aluminum, molybdenum, and silicon elements; IL6 expression was positively correlated with most PAHs. Stratification of data based on HAEC donor demographics suggests that these affect gene expression changes. Enrichment analysis indicated similarity with several deployment-related presumptive and reported diseases, including asthma, emphysema, and cancer of different organs.</p><p><strong>Conclusions: </strong>This study highlights that simulated burn pit smoke exposure of HAECs causes gene expression changes indicative of deployment-related diseases with more pronounced effects seen in smokers and females. 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引用次数: 0
摘要
背景:在部署期间暴露于军用燃烧坑烟雾与不同的呼吸道和非呼吸道疾病有关。然而,目前还缺乏将烟雾暴露与人类肺部健康联系起来的信息。本研究检测了模拟烧伤坑烟雾冷凝物对人体气道上皮细胞(HAECs)的影响,HAECs 来自 12 个供体(吸烟者/非吸烟者,生物女性/男性),在空气-液体界面培养,并暴露于三种模拟烧伤坑废物材料(纸板、胶合板和塑料)在两种燃烧条件下焚烧产生的冷凝物中:燃烧和火焰。使用大量 RNA 测序分析了细胞基因的表达,并使用多重免疫测定评估了基底层介质细胞因子的水平:结果:燃烧的烟雾凝结物引起了更多显著的差异表达基因(DEGs),其中胶合板燃烧的烟雾在改变基因表达和调节细胞因子释放方面最为有效。纸板和胶合板火焰冷凝物主要激活解毒途径,而塑料火焰则影响与抗微生物和炎症反应有关的基因。通过对烟雾冷凝物中的化学物质与基因表达之间的相关性分析来了解其潜在机制,结果发现含氧多环芳烃(PAHs)以及铝、钼和硅元素起着关键作用;IL6的表达与大多数PAHs呈正相关。根据 HAEC 供体的人口统计学特征对数据进行分层表明,这些因素会影响基因表达的变化。富集分析表明,这些基因与几种与部署相关的推测和报告疾病具有相似性,包括哮喘、肺气肿和不同器官的癌症:本研究强调,HAECs 暴露于模拟烧伤坑烟雾会导致基因表达变化,表明与部署相关的疾病,吸烟者和女性受到的影响更为明显。未来的研究还需要进一步确定性别和吸烟状况如何影响部署相关疾病。
Effects of simulated smoke condensate generated from combustion of selected military burn pit contents on human airway epithelial cells.
Background: Exposure to military burn pit smoke during deployment is associated with different respiratory and non-respiratory diseases. However, information linking smoke exposure to human pulmonary health is lacking. This study examined the effects of simulated burn pit smoke condensates on human airway epithelial cells (HAECs) from twelve donors (smokers/non-smokers, biological female/male) cultured at an air-liquid interface and exposed to condensates from three simulated burn pit waste materials (cardboard, plywood, and plastic) incinerated at two combustion conditions: smoldering and flaming. Cellular gene expression was analyzed using bulk RNA sequencing, and basolateral media cytokine levels were assessed using multiplex immunoassay.
Results: Flaming smoke condensates caused more significant differentially expressed genes (DEGs) with plywood flaming smoke being the most potent in altering gene expression and modulating cytokine release. Cardboard and plywood flaming condensates primarily activated detoxification pathways, whereas plastic flaming affected genes related to anti-microbial and inflammatory responses. Correlation analysis between smoke condensate chemicals and gene expression to understand the underlying mechanism revealed crucial role of oxygenated polycyclic aromatic hydrocarbons (PAHs) and aluminum, molybdenum, and silicon elements; IL6 expression was positively correlated with most PAHs. Stratification of data based on HAEC donor demographics suggests that these affect gene expression changes. Enrichment analysis indicated similarity with several deployment-related presumptive and reported diseases, including asthma, emphysema, and cancer of different organs.
Conclusions: This study highlights that simulated burn pit smoke exposure of HAECs causes gene expression changes indicative of deployment-related diseases with more pronounced effects seen in smokers and females. Future studies are needed to further characterize how sex and smoking status affect deployment-related diseases.
期刊介绍:
Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.