Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers

Abstract

Expression 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 48 hours, suggesting that 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.

An Official American Thoracic Society Workshop Report: Presentations and Discussion of the Sixth Jack Pepys Workshop on Asthma in the Workplace

“…Epithelial damage is reported with human DE exposure (including particles and gases) versus clean air (100, 101). The same authors showed an interaction with glutathione- S -transferase theta-1 and DE in the activation of cytotoxic T cells in lung lavage, and in the development of airflow limitation (with glutathione- S -transferase theta-1-null plus DE exposure) (100).…”

“…The same authors showed an interaction with glutathione- S -transferase theta-1 and DE in the activation of cytotoxic T cells in lung lavage, and in the development of airflow limitation (with glutathione- S -transferase theta-1-null plus DE exposure) (100). An epithelial epigenetic effect has been shown: acute exposure to DE and/or allergen alters expression of microRNA and genes, with effects on inflammatory markers associated with asthma (101, 102). There are methylation changes in airway epithelium after acute DE exposure, and exposure–exposure epigenetic interactions caused by DE with allergen exposure.…”

Aeroallergens in Canada: Distribution, Public Health Impacts, and Opportunities for Prevention

“…For example, gene–environment interactions have been demonstrated with changes in microRNA [3] and bronchial epithelial DNA methylation, after exposures to diesel exhaust [104]. For individuals with atopy-prone or immune modulated genotypes, environmental exposures play a role in the onset of an allergic disorder [105], including exposures to aeroallergens [2,106].…”

“…Air pollutants allow for easier penetration of pollen and spore allergens because they trigger damage to the airway mucociliary clearance mechanisms [128,141]. Particulate matter smaller than 2.5 μm (PM 2.5 ) reaches deeply in the lungs and acts as an adjuvant that increases production of IgE [3,151,152]. Furthermore, exposure to diesel exhaust is known to impact DNA methylation and impaired regulatory T-cell functions, two mechanisms relevant for the immune response [104].…”

“…This increase cannot be explained by genetic changes only [2]. Environmental exposure to air pollutants and aeroallergens have been hypothesized as potential causes for this steep increase, as the nature of these exposures have changed during a similar window of time [3]. …”