由选定的军事燃烧坑含量在人类气道上皮细胞上燃烧产生的模拟烟雾冷凝物的影响
Effects of simulated smoke condensate generated from combustion of selected military burn pit contents on human airway epithelial cells
影响因子:8.20000
分区:医学1区 Top / 毒理学1区
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
摘要
部署过程中暴露于军事烧伤坑中的烟雾与不同的呼吸道和非呼吸性疾病有关。但是，缺乏将烟雾暴露与人类肺部健康联系起来的信息。这项研究检查了在空气液体界面上培养的十二个供体（吸烟者/非吸烟者，生物女性/男性）的模拟燃烧坑烟雾冷凝物对人类气道上皮细胞（HAEC）的影响，并在三个模拟的烧伤坑垃圾材料（纸板，plywood，pywood，pywood和塑料）条件下暴露于冷凝物，在两个模拟的燃烧坑中和效果。使用大量RNA测序分析细胞基因表达，并使用多重免疫测定法对基底外侧培养基细胞因子水平进行评估。烟雾冷凝物引起了更重要的差异表达基因（DEG），而胶合板燃烧烟雾是改变基因表达和调节细胞因子释放的最有效的烟雾。纸板和胶合板燃烧的冷凝水主要激活排毒途径，而塑料燃烧的基因与抗微生物和炎症反应有关。烟雾凝聚力化学物质与基因表达之间的相关性分析，以了解潜在的机制表明氧化多环芳烃（PAHS）和铝，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数据分层表明这些影响基因表达的变化。富集分析表明，与部署相关的几种假定和报道的疾病相似，包括哮喘，肺气肿和不同器官的癌症。这项研究要点，这些疾病凸显了基因表达的模拟烧伤坑烟雾导致基因表达的变化，表明与部署相关的疾病具有更明显的疾病，在吸烟者和女性中看到了更明显的影响。需要进一步的研究来进一步表征性别和吸烟状况如何影响与部署相关的疾病。
Abstract
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.