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Rapid microRNA changes in airways of human volunteers after controlled exposure to air pollutants
Citation:
Kahle, J., K. Duncan, Mike Schmitt, B. Vallanat, A. Fisher, R. Devlin, AND D. Diaz-Sanchez. Rapid microRNA changes in airways of human volunteers after controlled exposure to air pollutants. Presented at American Thoracic Society.
Impact/Purpose:
This abstract highlights rapid epigenetic changes seen after controlled exposure to air pollution. The abstract is for a scientific audience and will provide an opportunity for scientific feedback regarding this work.
Description:
Introduction/Rationale: Exposure to air pollutants, including ozone and diesel exhaust (DE) are known to cause acute cardiopulmonary dysfunction; however, the molecular mechanisms underlying these changes remain elusive. One mechanism for rapid regulation of multiple genes is alteration of miRNAs, which modulate the expression of many genes post-transcriptionally. We hypothesized that in vivo exposure to ozone or DE could rapidly change miRNA profiles in airway cells and may partially explain the acute physiological response to these pollutants. Methods: Healthy volunteers were exposed to clean air (CA), DE (300 µg/m3) or ozone (0.3ppm) for two hours in a controlled chamber environment with intermittent exercise on three separate exposure days. The order of the exposures was randomized and they were seperated by at least four weeks. Cytological brush samples of bronchial epithelial cells (BECs) and bronchoalveolar lavage fluid (BALF) were collected when subjects underwent bronchoscopy 24 hrs after each exposure. Total RNA from BALF cell pellets, consisting of greater than 90% alveolar macrophages (MACs), and BECs were purified, quantified and passed quality control before hybridization to Agilent miRNA arrays. Data was analyzed using PartekGS and filtered for ≥1.5 fold-change (fc) and p<0.05. Results: After confirming that the BECs and MACs had different miRNA profiles, they were analyzed independently for miRNAs altered after exposure to either DE or ozone, relative to CA. In BECs, altered miRNAs were mostly down-regulated after both DE (79%) and ozone (100%) exposure, including miR-1246 (DE, fc=-1.7, p=.022) and miR-449a (ozone, fc=-2.1, p=0.00082) and -449b (ozone, fc=-2.0, p=0.0024). Interestingly, miR-1246 has previously been shown to target CFTR (the gene mutated in cystic fibrosis (CF)) and epidemiological studies have linked CF patient exposure to particulate matter, of which DE is a component, to increased acute CF exacerbations. M