选定的军用烧伤坑内容物燃烧产生的模拟烟雾冷凝物对人体气道上皮细胞的影响。
Effects of simulated smoke condensate generated from combustion of selected military burn pit contents on human airway epithelial cells.
发表日期:2024 Oct 08
作者:
Arunava Ghosh, Keith L Rogers, Samuel C Gallant, Yong Ho Kim, Julia E Rager, M Ian Gilmour, Scott H Randell, Ilona Jaspers
来源:
Particle and Fibre Toxicology
摘要:
在部署期间暴露于军事烧伤坑烟雾与不同的呼吸系统和非呼吸系统疾病有关。然而,缺乏将烟雾暴露与人类肺部健康联系起来的信息。本研究研究了模拟烧伤坑烟雾冷凝物对来自 12 名供体(吸烟者/非吸烟者、生物女性/男性)的人气道上皮细胞 (HAEC) 的影响,这些细胞在气液界面培养并暴露于来自三个模拟烧伤坑的冷凝物在两种燃烧条件下焚烧的废料(纸板、胶合板和塑料):阴燃和燃烧。使用批量 RNA 测序分析细胞基因表达,并使用多重免疫测定评估基底外侧介质细胞因子水平。火焰烟雾凝结物引起更显着的差异表达基因 (DEG),其中胶合板火焰烟雾在改变基因表达和调节细胞因子释放方面最有效。纸板和胶合板燃烧冷凝物主要激活解毒途径,而塑料燃烧影响与抗菌和炎症反应相关的基因。烟雾凝结物化学物质与基因表达之间的相关性分析,以了解其潜在机制,揭示了含氧多环芳烃 (PAH) 以及铝、钼和硅元素的关键作用; IL6 表达与大多数 PAH 呈正相关。基于 HAEC 供体人口统计数据的分层表明,这些因素会影响基因表达的变化。富集分析表明与几种与部署相关的假定和报告的疾病相似,包括哮喘、肺气肿和不同器官的癌症。这项研究强调,HAEC 的模拟烧坑烟雾暴露会导致基因表达变化,表明与部署相关的疾病具有更明显的影响见于吸烟者和女性。未来的研究需要进一步确定性别和吸烟状况如何影响部署相关疾病。© 2024。作者。
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.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.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.© 2024. The Author(s).