The ability of air pollution to induce acute exacerbation of asthma is well documented. However, the ability of ozone (O3), the most reactive gaseous component of air pollution, to function as a modulator during sensitization is not well established. C57BL/6 J male mice were intranasally sensitized to house dust mite (HDM) (40 μg/kg) for 3 weeks on alternate days in parallel with once-a-week O3 exposure (1 ppm). Mice were euthanized 24 h following the last HDM challenge. Lung lavage, histology, lung function (both forced oscillation and forced expiration-based), immune cell profiling, inflammation (pulmonary and systemic), and immunoglobulin production were assessed. Compared to HDM alone, HDM + O3 leads to a significant increase in peribronchial inflammation (p < 0.01), perivascular inflammation (p < 0.001) and methacholine-provoked large airway hyperreactivity (p < 0.05). Serum total IgG and IgE and HDM-specific IgG1 were 3–5 times greater in HDM + O3 co-exposure compared to PBS and O3-exposed groups. An increase in activated/mature lung total and monocyte-derived dendritic cells (p < 0.05) as well as T-activated, and T memory lymphocyte subset numbers (p < 0.05) were noted in the HDM + O3 group compared to HDM alone group. Concurrent O3 inhalation and HDM sensitization also caused significantly greater (p < 0.05) lung tissue interleukin-17 pathway gene expression and mediator levels in the serum. Redox imbalance was manifested by impaired lung antioxidant defense and increased oxidants. O3 inhalation during allergic sensitization coalesces in generating a significantly worse TH17 asthmatic phenotype.

中文翻译：

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屋尘螨诱导致敏期间间歇性吸入臭氧可导致不良哮喘表型


空气污染引起哮喘急性发作的能力已有充分记录。然而，臭氧 (O3)（空气污染中最具反应性的气态成分）在致敏过程中充当调节剂的能力尚未确定。 C57BL/6 J 雄性小鼠每隔一天鼻内对屋尘螨 (HDM) (40 μg/kg) 致敏，持续 3 周，同时每周暴露一次 O3 (1 ppm)。最后一次 HDM 挑战后 24 小时对小鼠实施安乐死。评估了肺灌洗、组织学、肺功能（基于强制振荡和强制呼气）、免疫细胞分析、炎症（肺部和全身）和免疫球蛋白的产生。与单独使用 HDM 相比，HDM + O3 会导致支气管周围炎症 (p < 0.01)、血管周围炎症 (p < 0.001) 和醋甲胆碱引起的大气道高反应性 (p < 0.05) 显着增加。与 PBS 和 O3 暴露组相比，HDM + O3 共暴露组的血清总 IgG 和 IgE 以及 HDM 特异性 IgG1 增加了 3-5 倍。与 HDM 相比，HDM + O3 组中活化/成熟肺总数和单核细胞衍生的树突细胞 (p < 0.05) 以及 T 活化和 T 记忆淋巴细胞亚群数量 (p < 0.05) 有所增加单独组。同时吸入 O3 和 HDM 致敏还导致肺组织白细胞介素 17 通路基因表达和血清中介质水平显着升高 (p < 0.05)。氧化还原失衡表现为肺部抗氧化防御受损和氧化剂增加。过敏致敏期间吸入 O3 会合并产生明显更差的 TH17 哮喘表型。