Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot OX11 0RQ, UK; The National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Health Impact of Environmental Hazards at King's College London in partnership with Public Health England (PHE) in collaboration with Imperial College London, UK.
Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot OX11 0RQ, UK; The National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Health Impact of Environmental Hazards at King's College London in partnership with Public Health England (PHE) in collaboration with Imperial College London, UK.
Toxicol In Vitro. 2017 Dec;45(Pt 3):409-416. doi: 10.1016/j.tiv.2017.06.023. Epub 2017 Jun 24.
Air pollution affects a large proportion of the population particularly in urban areas, with diesel particulates recognised as particular causes for concern in respiratory conditions such as asthma. In this study we examined the response of human primary airway epithelial cells to diesel particulate chemical extracts (DE) and characterised gene expression alterations using RNA-SEQ. Using the antagonist CH223191, DE induced CYP1A1 and attenuation of CXCL10 among other genes were observed to be aryl hydrocarbon receptor dependent. Basal and toll like receptor dependent protein levels for CXCL10 were markedly reduced. Investigation of similar regulation in plasmacytoid dendritic GEN2.2 cells did not show DE dependent regulation of CXCL10. Instillation of DE into mice to recapitulate airway epithelial exposure to chemical extracts in an in vivo setting failed to demonstrate a reduction in CXCL10. There was however an increase in the Th2 type epithelial cell derived inflammatory mediators TSLP and SERPINB2. We also observed an increased macrophages and a decrease in the proportion of lymphocytes in bronchoalveolar lavage fluid. CXCL10 can play a role in allergic airway disease through recruitment of Th1 type CD4+ T-cells, which can act to counterbalance Th2 type allergic responses. Modulation of such chemokines within the airway epithelium may represent a mechanism through which pollutant material can modify respiratory conditions such as allergic asthma.
空气污染影响了很大一部分人口，特别是在城市地区，柴油颗粒被认为是哮喘等呼吸道疾病的特别关注原因。在这项研究中，我们研究了人类原代气道上皮细胞对柴油颗粒化学提取物（DE）的反应，并使用 RNA-SEQ 对基因表达变化进行了表征。使用拮抗剂 CH223191，观察到 DE 诱导的 CYP1A1 和 CXCL10 的衰减等基因是芳烃受体依赖性的。CXCL10 的基础和 Toll 样受体依赖性蛋白水平明显降低。在浆细胞样树突状细胞 GEN2.2 中对类似调节的研究表明，CXCL10 不受 DE 依赖调节。在体内环境中用 DE 滴注小鼠以重现气道上皮细胞暴露于化学提取物的实验未能证明 CXCL10 的减少。然而，Th2 型上皮细胞衍生的炎症介质 TSLP 和 SERPINB2 的增加。我们还观察到肺泡灌洗液中的巨噬细胞增加和淋巴细胞比例减少。CXCL10 通过招募 Th1 型 CD4+ T 细胞在过敏性气道疾病中发挥作用，这可以抵消 Th2 型过敏反应。气道上皮细胞内这种趋化因子的调节可能是污染物材料可以改变过敏性哮喘等呼吸道疾病的机制。
