交通相关空气污染(TRAP)与过敏性哮喘相关的证据越来越多,但这种关联的潜在机制仍不清楚.气道上皮是暴露于TRAP的主要组织,因此,了解其与TRAP和过敏原的相互作用非常重要。柴油排气(DE),陷阱的范例,颗粒物质(PM)和气体。现代柴油发动机通常具有催化柴油颗粒过滤器,以减少PM输出,但是这些可能会增加气体浓度,它们对人类健康的好处是不能假设的。我们做了一个随机的,双盲,使用我们独特的体内人体暴露系统进行交叉研究,以研究DE和过敏原共同暴露的影响,有或没有颗粒消耗作为催化柴油颗粒过滤器的代理,气道上皮转录组。参与者在过敏原吸入攻击前暴露2小时,每个接受过滤空气和盐水(FA-S),过滤空气和过敏原(FA-A),DE和过敏原(DE-A),或颗粒耗尽的DE和过敏原(PDDE-A),在四个不同的场合,每个间隔4周的冲洗期。每次暴露后48小时收集支气管内刷,并对总RNA进行测序。使用DESeq2鉴定差异表达基因(DEGs),随后进行GO富集和途径分析。FA-A,DE-A,和PDDE-A暴露显著调节基因相对于FA-S,确定了462个独特的DEG。FA-A唯一调制的最高数字(^178,^155),其次是DE-A(^44,^23),然后PDDE-A曝光(^15,^2);6个DEG(^4,^2)被所有三个条件调制。与DE-A暴露相比,PDDE-A暴露导致285DEG的调制,进一步揭示了26个生物过程GO术语,包括“细胞对趋化因子的反应”和“炎症反应”。对柴油机废气和过敏原共暴露的转录上皮反应富含炎症介质,其模式随着粒子耗尽而改变。
The evidence associating traffic-related air pollution (TRAP) with allergic asthma is growing, but the underlying mechanisms for this association remain unclear. The airway epithelium is the primary tissue exposed to TRAP, hence understanding its interactions with TRAP and allergen is important. Diesel exhaust (DE), a paradigm of TRAP, consists of particulate matter (PM) and gases. Modern diesel engines often have catalytic diesel particulate filters to reduce PM output, but these may increase gaseous concentrations, and their benefits on human health cannot be assumed. We conducted a randomized, double-blinded, crossover study using our unique in vivo human exposure system to investigate the effects of DE and allergen co-exposure, with or without particle depletion as a proxy for catalytic diesel particulate filters, on the airway epithelial transcriptome. Participants were exposed for 2 h before an allergen inhalation challenge, with each receiving filtered air and saline (FA-S), filtered air and allergen (FA-A), DE and allergen (DE-A), or particle-depleted DE and allergen (PDDE-A), over four different occasions, each separated by a 4-week washout period. Endobronchial brushings were collected 48 h after each exposure, and total RNA was sequenced. Differentially expressed genes (DEGs) were identified using DESeq2, followed by GO enrichment and pathway analysis. FA-A, DE-A, and PDDE-A exposures significantly modulated genes relative to FA-S, with 462 unique DEGs identified. FA-A uniquely modulated the highest number (↑178, ↓155), followed by DE-A (↑44, ↓23), and then PDDE-A exposure (↑15, ↓2); 6 DEGs (↑4, ↓2) were modulated by all three conditions. Exposure to PDDE-A resulted in modulation of 285 DEGs compared to DE-A exposure, further revealing 26 biological process GO terms, including \"cellular response to chemokine\" and \"inflammatory response\". The transcriptional epithelial response to diesel exhaust and allergen co-exposure is enriched in inflammatory mediators, the pattern of which is altered upon particle depletion.