Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Ozone Exposure Alters MicroRNA Expression Profiles in Humans

ABSTRACT: We set out to test the hypothesis that ozone inhalation exposure significantly alters miRNA expression profiles within the airway of humans. Adult human volunteers were exposed to 0.4 ppm ozone for two hours. Induced sputum samples were collected from each subject 48 hours pre-exposure and 6 hours post-exposure. Genome-wide miRNA expression profiles were evaluated using microarray analysis. Twenty healthy non-asthmatic adult subjects aged 18 – 37 years, with no history of smoking in the past 10 years, completed the study. The ozone exposures were conducted in an exposure chamber. Each subject was exposed to 0.4 ppm ozone for two hours while performing four 15-minute sessions of intermittent moderate exercise (expiratory minute ventilation, 30–40 L/min) on a treadmill, separated by 15 minutes of seated rest. Induced sputum samples were collected from each subject 48 hours pre-exposure and 6 hours post-exposure. RNA samples were homogenized in TRIzol, and extracted according to standard TRIzol protocol. RNA was labeled and hybridized to the Agilent Human miRNA Microarray (v1.0).

ORGANISM(S): Homo sapiens

SUBMITTER: Rebecca Fry

PROVIDER: E-GEOD-47977 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Fry Rebecca C RC Rager Julia E JE Bauer Rebecca R Sebastian Elizabeth E Peden David B DB Jaspers Ilona I Alexis Neil E NE

American journal of physiology. Lung cellular and molecular physiology 20140425 12

Ozone (O3) 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 O3-induced health effects remain understudied. MicroRNAs (miRNAs) are epigenetic regulators of genomic response to environmental insults and unstudied in relationship to O3 inhalation exposure. Our objective was to test whether O3 inhalation exposure significantly alters mi ...[more]

PMID: 24771714

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Project description:Rationale: Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases TLR4-mediated response to subsequent stimulation with lipopolysaccharide (LPS). To further explore the pulmonary innate immune response to ozone exposure, we investigated the effect of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Methods: Bronchoalveolar lavage (BAL) and lungs were harvested from C57Bl/6 mice after exposure to ozone or filtered air followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the BAL, surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. Results: We demonstrate an increased BAL cell influx, increased IL-6 and KC, and decreased MIP-1α and TNF-α in response to Pam3CYS as a result of ozone pre-exposure. We also observed increased cell surface expression of TLR4, TLR2 and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in expression of genes related to injury repair and cell cycle as a result of ozone exposure. When comparing Pam3CYS treated animals to saline treated animals with or without ozone, genes associated with inflammation were significantly increased. Potentially novel ozone exposure candidate genes (CCK, RELM-α and β) were identified. Conclusion: Our results extend previous findings with ozone/LPS to other TLRs PAMPs and suggest that ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level. Mice were exposed to either 2ppm ozone or filtered air (FA) for 3 hours. 24 hours following ozone exposure, mice from either the ozone or FA group were treated intratracheally with either 100ug of Pam3CYS in saline or saline alone. Animals were euthanized 4 or 24 hours post-Pam3CYS exposure. RNA from whole lung tissue from 4 animals per group was profiled.

Dataset Information

Ozone Exposure Alters MicroRNA Expression Profiles in Humans

Publications

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

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