AI Article Synopsis
- Traffic-related air pollution is linked to worsening asthma, possibly due to changes in DNA methylation caused by environmental exposure.
- The study examined how allergen and diesel exhaust affect global DNA methylation and its regulating enzymes in the airways of participants with varying asthma responses.
- Findings revealed that specific DNA methylation enzymes and their levels differ among individuals with or without airway hyperresponsiveness and influence inflammation responses, suggesting they could be important for diagnosing and understanding asthma severity.
Article Abstract
Background: 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.
Objectives: We sought to assess the effects of allergen and diesel exhaust (DE) exposures on global DNAm and its regulation enzymes in human airway epithelium.
Methods: 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.
Results: 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.
Conclusions: 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.
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| http://dx.doi.org/10.1016/j.jaci.2020.08.044 | DOI Listing |
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