Diesel exhaust and allergen modulate miRNA and RNA in intact human epithelium

Publication date: Available online 24 April 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Christopher F. Rider, Masatsugu Yamamoto, Oliver P. Günther, Jeremy A. Hirota, Amrit Singh, Scott J. Tebbutt, Chris Carlsten
BackgroundAir pollution's association with asthma may be due its augmentation of allergenic effects, but the role of miRNA and gene expression in this synergy is unknown.ObjectiveTo determine whether exposure to allergen, diesel exhaust (DE) or co-exposures modulates miRNA, gene expression or inflammatory pathways and whether these measurements are correlated.MethodsFifteen atopic participants completed this controlled study of 2h of filtered air (FA) or DE (300 μg PM2.5/m³) exposure, followed by saline-controlled segmental bronchial allergen challenge. Gene and microRNA expression in bronchial brushings and lung inflammatory markers were measured 48h later, in study arms separated by approximately 4 weeks. Expression of miRNAs, mRNAs and inflammatory markers and their interrelationships were determined using regression.ResultsRobust linear models indicated that diesel exhaust plus saline and diesel exhaust plus allergen significantly modulated the highest number of miRNAs and mRNAs, respectively, relative to control (filtered air plus saline). In mixed models, allergen exposure significantly modulated (q≤0.2) miRNAs including miR-183-5p, miR-324-5p and miR-132-3p and genes including NFKBIZ and CDKN1A, but diesel exhaust did not significantly modify this allergenic effect. Repression of CDKN1A by allergen-induced miR-132-3p may contribute to shedding of BECs.ConclusionsExpression of specific miRNAs and genes associated with bronchial immune responses were significantly modulated by DE or allergen. However, DE did not augment the effect of allergen at 48h, suggesting adjuvancy may be transient or require higher or prolonged exposure. In silico analysis suggested a possible mechanism contributing to epithelial wall damage following allergen exposure. ClinicalTrials.gov Identifier: NCT01792232

Teaser

In vivo exposure to allergen, diesel exhaust or co-exposures modulated miRNA and mRNA expression in human bronchial epithelial cells (BECs). Allergen induced gene expression correlated with lung inflammatory cell recruitment and BEC shedding.


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