模拟烟雾冷凝物对人体呼吸道上皮细胞的影响：由特定军事焚烧坑内容物燃烧产生

Effects of simulated smoke condensate generated from combustion of selected military burn pit contents on human airway epithelial cells

Particle and Fibre Toxicology

影响因子:8.2

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

DOI: 10.1186/s12989-024-00604-7

摘要

部署期间暴露于军事焚烧坑烟雾与多种呼吸及非呼吸系统疾病相关。然而，目前缺乏关于烟雾暴露与人体肺部健康关系的资料。本研究考察了由三种模拟焚烧坑废弃物（纸板、胶合板和塑料）在两种燃烧条件（闷烧和明火燃烧）焚烧产生的烟雾冷凝物对来自12名供体（吸烟者/非吸烟者，生物性别为女性/男性）的人类呼吸道上皮细胞（HAECs）的影响。细胞基因表达通过Bulk RNA测序分析，基础膜面细胞因子水平则通过多重免疫分析检测。明火燃烧烟雾冷凝物引起了更显著的差异表达基因（DEGs），其中胶合板燃烧烟雾在改变基因表达和调节细胞因子释放方面最为有效。纸板和胶合板明火燃烧冷凝物主要激活解毒通路，而塑料燃烧则影响与抗微生物和炎症反应相关的基因。通过分析烟雾冷凝物化学成分与基因表达的相关性，揭示氧化多环芳香烃（PAHs）以及铝、钼和硅元素起着关键作用；IL6的表达与大部分PAHs呈正相关。根据供体的性别和年龄进行的分层分析表明，这些因素影响基因表达变化。富集分析显示与多种部署相关的假定和已报道疾病具有相似性，包括哮喘、肺气肿和不同器官的癌症。本研究强调模拟焚烧坑烟雾暴露会引起表明部署相关疾病的基因表达变化，且在吸烟者和女性中效果更为明显。未来研究需进一步探讨性别和吸烟状态如何影响部署相关疾病的发生。

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.