Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation.
Allergic disease affects 30% to 40% of the world's population, and its development is determined by the interplay between environmental and inherited factors. Air pollution, primarily consisting of diesel exhaust emissions, has increased at a similar rate to allergic disease. Exposure to diesel exhaust may play a role in the development and progression of allergic disease, in particular allergic respiratory disease. One potential mechanism underlying the connection between air pollution and increased allergic disease incidence is DNA methylation, an epigenetic process with the capacity to integrate gene-environment interactions.



We sought to investigate the effect of allergen and diesel exhaust exposure on bronchial epithelial DNA methylation.



We performed a randomized crossover-controlled exposure study to allergen and diesel exhaust in humans, and measured single-site (CpG) resolution global DNA methylation in bronchial epithelial cells.



Exposure to allergen alone, diesel exhaust alone, or allergen and diesel exhaust together (coexposure) led to significant changes in 7 CpG sites at 48 hours. However, when the same lung was exposed to allergen and diesel exhaust but separated by approximately 4 weeks, significant changes in more than 500 sites were observed. Furthermore, sites of differential methylation differed depending on which exposure was experienced first. Functional analysis of differentially methylated CpG sites found genes involved in transcription factor activity, protein metabolism, cell adhesion, and vascular development, among others.



These findings suggest that specific exposures can prime the lung for changes in DNA methylation induced by a subsequent insult.
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Rachel L
RL
Clifford
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Meaghan J
MJ
Jones
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Julia L
JL
MacIsaac
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Lisa M
LM
McEwen
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Sarah J
SJ
Goodman
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada; Canadian Institute for Advanced Research, Toronto, Ontario, Canada.
Sara
S
Mostafavi
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Canadian Institute for Advanced Research, Toronto, Ontario, Canada; Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
Michael S
MS
Kobor
Air Pollution Exposure Laboratory, Chan-Yeung Centre for Occupational and Environmental Lung Disease, Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: carlsten@mail.ubc.ca.
Chris
C
Carlsten
D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D000485:Allergens / Q000633:toxicity*; D039741:Antigens, Dermatophagoides / Q000633:toxicity; D001249:Asthma / Q000235:genetics / Q000378:metabolism; D029662:Betula / Q000276:immunology; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D031784:Phleum / Q000276:immunology; D010940:Plant Proteins / Q000633:toxicity; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*; D055815:Young Adult
D000393:Air Pollutants; D000485:Allergens; D039741:Antigens, Dermatophagoides; D010940:Plant Proteins; D001335:Vehicle Emissions
Allergen; DNA methylation; air pollution; diesel exhaust; epigenetics; particulate matter