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Diesel exhaust particle exposure reduces expression of the epithelial tight junction protein Tricellulin
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2020-10-15 , DOI: 10.1186/s12989-020-00383-x
Timothy Smyth 1 , Janelle Veazey 2 , Sophia Eliseeva 3 , David Chalupa 1 , Alison Elder 1 , Steve N Georas 1, 2, 3
Affiliation  

While exposure to diesel exhaust particles has been linked to aberrant immune responses in allergic diseases such as asthma, little attention has been paid to their effects on the airway epithelial barrier. In this study, we sought to determine the effect of diesel exhaust exposure on airway epithelial barrier function and composition using in vitro and in vivo model systems. 16HBE14o- human bronchial epithelial cells were grown on collagen coated Transwell inserts and exposed to 5 to 50 μg/cm2 SRM 2975 diesel particulate matter (DEP) suspended in cell culture medium or vehicle controls. Changes in barrier function were assessed by measuring transepithelial electrical resistance (TEER) and permeability to 4 kDa FITC Dextran. Neonatal BALB/c mice were exposed to aerosolized DEP (255 ± 89 μg/m3; 2 h per day for 5 days) and changes in the tight junction protein Tricellulin were assessed 2 weeks post exposure. A six-hour incubation of epithelial cells with diesel exhaust particles caused a significant concentration-dependent reduction in epithelial barrier integrity as measured by decreased TEER and increased permeability to 4 kDa FITC-Dextran. This reduction in epithelial barrier integrity corresponded to a significant reduction in expression of the tight junction protein Tricellulin. siRNA mediated knockdown of Tricellulin recapitulated changes in barrier function caused by DEP exposure. Neonatal exposure to aerosolized DEP caused a significant reduction in lung Tricellulin 2 weeks post exposure at both the protein and mRNA level. Short term exposure to DEP causes a significant reduction in epithelial barrier integrity through a reduction in the tight junction protein Tricellulin. Neonatal exposure to aerosolized DEP caused a significant and sustained reduction in Tricellulin protein and mRNA in the lung, suggesting that early life exposure to inhaled DEP may cause lasting changes in airway epithelial barrier function.

中文翻译:

柴油机排气颗粒暴露会降低上皮紧密连接蛋白Tricellulin的表达

尽管暴露于柴油机排气颗粒与过敏性疾病(例如哮喘)中异常的免疫反应有关,但很少关注其对气道上皮屏障的影响。在这项研究中,我们试图使用体外和体内模型系统确定暴露于柴油机废气对气道上皮屏障功能和成分的影响。16HBE14o-人支气管上皮细胞在胶原蛋白包被的Transwell插入片段上生长,并暴露于5至50μg/ cm2 SRM 2975柴油颗粒物质(DEP),悬浮在细胞培养基或媒介物对照中。通过测量跨上皮电阻(TEER)和对4 kDa FITC葡聚糖的渗透性来评估屏障功能的变化。新生BALB / c小鼠暴露于雾化DEP(255±89μg/ m3; 每天2小时,共5天),并在暴露后2周评估紧密连接蛋白Tricellulin的变化。上皮细胞与柴油机尾气颗粒一起孵育六小时会导致上皮屏障完整性的浓度依赖性显着降低,这可以通过减少TEER和增加对4 kDa FITC-Dextran的渗透性来衡量。上皮屏障完整性的这种降低对应于紧密连接蛋白Tricellulin的表达的显着降低。siRNA介导的Tricellulin的敲低概括了DEP暴露引起的屏障功能变化。新生儿暴露于气溶胶​​化的DEP后,在蛋白质和mRNA水平暴露后2周,肺Tricellulin明显减少。短期暴露于DEP会导致紧密连接蛋白Tricellulin减少,导致上皮屏障完整性显着降低。新生儿暴露于雾化的DEP中会导致肺中Tricellulin蛋白和mRNA的持续显着降低,这表明生命早期暴露于吸入的DEP可能会导致气道上皮屏障功能的持久变化。
更新日期:2020-10-16
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