Hang Li1, Min Hyung Ryu2, Christopher F Rider2, Wayne Tse2, Rachel L Clifford3, Maria J Aristizabal4, Weiping Wen5, Chris Carlsten6. 1. 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. 2. Air Pollution Exposure Laboratory, Department of Medicine, Division of Respiratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada. 3. Nottingham NIHR Biomedical Research Centre, Nottingham MRC Molecular Pathology Node, Division of Respiratory Medicine, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital, Nottingham, United Kingdom. 4. Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada; Child and Brain Development Program, Canadian Institute for Advanced Research (CIFAR), Toronto, Ontario, Canada. 5. Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: wenwp@mail.sysu.edu.cn. 6. Air Pollution Exposure Laboratory, Department of Medicine, Division of Respiratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: carlsten@mail.ubc.ca.
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.
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.
Authors: Samantha Goodman; Grace Chappell; Kathryn Z Guyton; Igor P Pogribny; Ivan Rusyn Journal: Mutat Res Rev Mutat Res Date: 2021-12-09 Impact factor: 7.015
Authors: Steven K Huang; Priya Tripathi; Lada A Koneva; Raymond G Cavalcante; Nathan Craig; Anne M Scruggs; Maureen A Sartor; Furong Deng; Yahong Chen Journal: Environ Epigenet Date: 2021-02-28