Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; Air Pollution Exposure Laboratory, Department of Medicine, Division of Respiratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
Air Pollution Exposure Laboratory, Department of Medicine, Division of Respiratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
J Allergy Clin Immunol. 2021 May;147(5):1671-1682. doi: 10.1016/j.jaci.2020.08.044. Epub 2020 Oct 15.
Epidemiological data show that traffic-related air pollution contributes to the increasing prevalence and severity of asthma. DNA methylation (DNAm) changes may elucidate adverse health effects of environmental exposures.
We sought to assess the effects of allergen and diesel exhaust (DE) exposures on global DNAm and its regulation enzymes in human airway epithelium.
A total of 11 participants, including 7 with and 4 without airway hyperresponsiveness, were recruited for a randomized, double-blind crossover study. Each participant had 3 exposures: filtered air + saline, filtered air + allergen, and DE + allergen. Forty-eight hours postexposure, endobronchial biopsies and bronchoalveolar lavages were collected. Levels of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, 5-methylcytosine, and 5-hydroxymethylcytosine were determined by immunohistochemistry. Cytokines and chemokines in bronchoalveolar lavages were measured by electrochemiluminescence multiplex assays.
Predominant DNMT (the most abundant among DNMT1, DNMT3A, and DNMT3B) and predominant TET (the most abundant among TET1, TET2, and TET3) were participant-dependent. 5-Methylcytosine and its regulation enzymes differed between participants with and without airway hyperresponsiveness at baseline (filtered air + saline) and in response to allergen challenge (regardless of DE exposure). Predominant DNMT and predominant TET correlated with lung function. Allergen challenge effect on IL-8 in bronchoalveolar lavages was modified by TET2 baseline levels in the epithelium.
Response to allergen challenge is associated with key DNAm regulation enzymes. This relationship is generally unaltered by DE coexposure but is rather dependent on airway hyperresponsiveness status. These enzymes therefore warranted further inquiry regarding their potential in diagnosis, prognosis, and treatment of asthma.
流行病学数据表明，与交通相关的空气污染导致哮喘的发病率和严重程度不断上升。DNA 甲基化（DNAm）的改变可能阐明环境暴露对健康的不良影响。
我们旨在评估过敏原和柴油废气（DE）暴露对人呼吸道上皮细胞中全基因组 DNAm 及其调控酶的影响。
共招募了 11 名参与者，包括 7 名气道高反应性和 4 名无气道高反应性者，进行随机、双盲交叉研究。每位参与者接受 3 种暴露：过滤空气+生理盐水、过滤空气+过敏原、DE+过敏原。暴露后 48 小时，收集支气管活检和支气管肺泡灌洗标本。通过免疫组化测定 DNA 甲基转移酶（DNMTs）和 ten-eleven 转位（TET）酶、5-甲基胞嘧啶和 5-羟甲基胞嘧啶的水平。通过电化学发光多重分析测定支气管肺泡灌洗液中的细胞因子和趋化因子。
主要的 DNMT（DNMT1、DNMT3A 和 DNMT3B 中最丰富的一种）和主要的 TET（TET1、TET2 和 TET3 中最丰富的一种）因参与者而异。在基线（过滤空气+生理盐水）和过敏原刺激时（无论 DE 暴露如何），5-甲基胞嘧啶及其调控酶在气道高反应性和无气道高反应性的参与者之间存在差异。主要的 DNMT 和主要的 TET 与肺功能相关。上皮细胞中 TET2 基线水平改变了过敏原刺激对支气管肺泡灌洗液中白细胞介素 8 的影响。
对过敏原刺激的反应与关键的 DNAm 调控酶有关。这种关系一般不受 DE 共同暴露的影响，而是依赖于气道高反应性状态。因此，这些酶值得进一步研究，以了解其在哮喘诊断、预后和治疗中的潜在作用。
