EPA Science Inventory

Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects

Citation:

Fry, R., J. Rager, R. Bauer, E. Sebastian, D. Peden, I. Jaspers, AND N. Alexis. Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects. American Journal of Physiology - Lung Cellular and Molecular Physiology. American Physiological Society, Bethesda, MD, 306(12):L1129-L1137, (2014).

Description:

Ozone (03) is a criteria air pollutant that is associated with numerous adverse health effects, including altered respiratory immune responses. Despite its deleterious health effects, possible epigenetic mechanisms underlying 03-induced health effects remain understudied. MicroRNAs (miRNAs) are epigenetic regulators of genomic response to environmental insults and unstudied in relationship to 03 inhalation exposure. Our objective was to test whether 03 inhalation exposure significantly alters miRNA expression profiles within the human bronchial airways. Twenty healthy adult human volunteers were exposed to 0.4 ppm 03 for 2 h. Induced sputum samples were collected from each subject 48 h preexposure and 6 h postexposure for evaluation of miRNA expression and markers of inflammation in the airways. Genomewide miRNA expression profiles were evaluated by microarray analysis, and in silico predicted mRNA targets of the 03-responsive miRNAs were identified and validated against previously measured 03-induced changes in mRNA targets. Biological network analysis was performed on the 03-associated miRNAs and mRNA targets to reveal potential associated response signaling and functional enrichment. Expression analysis of the sputum samples revealed that 03 exposure significantly increased the expression levels of 10 miRNAs, namely miR-132, miR-143, miR-145, miR-199a*, miR_-199b-5p, miR-222, miR-223, miR-25, miR-424, and miR-582-5p. The miRNAs and their predicted targets were associated with a diverse range of biological functions and disease signatures, noted among them inflammation and immune-related disease. The present study shows that 03 inhalation exposure disrupts select miRNA expression profiles that are associated with inflammatory and immune response signaling. These findings provide novel insight into epigenetic regulation of resoonses to 03 exposure.

Purpose/Objective:

Objectives: To test whether 03 inhalation exposure significantly alters miRNA expression profiles within the human bronchial airways.

URLs/Downloads:

ORD-008887-FINAL ABSTRACT.PDF   (PDF,NA pp, 172.459 KB,  about PDF)

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 08/28/2014
Completion Date: 08/28/2014
Record Last Revised: 09/24/2014
Record Created: 08/28/2014
Record Released: 08/28/2014
OMB Category: Other
Record ID: 285048

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

ENVIRONMENTAL PUBLIC HEALTH DIVISION