Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation

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• 作者：Rachel L. Clifford ; PhD^a ; ^&lowast ; ; Meaghan J. Jones ; PhD^a ; Julia L. MacIsaac ; PhD^a ; Lisa M. McEwen ; BSc^a ; Sarah J. Goodman ; BSc^a ; Sara Mostafavi ; PhD^a ; ^b ; ^c ; Michael S. Kobor ; PhD^a ; ^c ; ^d ; ^&Dagger ; ; Chris Carlsten ; MD^e ; ^&Dagger ; ; ^{carlsten@mail.ubc.ca}
• 关键词：Allergen ; particulate matter ; diesel exhaust ; air pollution ; epigenetics ; DNA methylation
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：139
• 期：1
• 页码：112-121
• 全文大小：1319 K
• 卷排序：139

文摘

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.ObjectiveWe sought to investigate the effect of allergen and diesel exhaust exposure on bronchial epithelial DNA methylation.MethodsWe 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.ResultsExposure 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.ConclusionsThese findings suggest that specific exposures can prime the lung for changes in DNA methylation induced by a subsequent insult.