Dataset Information

Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter.

ABSTRACT:

Background

Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 (FOXP3) gene promoter, a proposed biomarker of Treg activity. We hypothesized that active urban children would have lower FOXP3 promoter methylation, associated with better lung function compared to non-active children. We also hypothesized that this relationship would be attenuated by high exposure to the air pollutant black carbon (BC).

Methods

We performed a cross-sectional study of 135 children ages 9-14 who live in New York City. Activity was measured across 6 days. BC exposure was assessed by personal monitors worn for two 24-h periods, followed by lung function assessment. Buccal swabs were collected for DNA methylation analysis of three regions (six CpG sites) in the FOXP3 promoter.

Results

In multivariable regression models, overall, there was no significant relationship between physical activity and FOXP3 promoter methylation (p?>?0.05). However, in stratified analyses, among children with higher BC exposure (?1200 ng/m³), physical activity was associated with 2.37% lower methylation in promoter 2 (CpGs -77, -65, and -58) (?_estimate?=?-2.37%, p??_estimate?=?0.54%, p?>?0.05). Differences across strata were statistically significant (p_interaction?=?0.04). Among all children, after controlling for BC concentration, promoter 2 methylation was associated with reduced FEV₁/FVC (?_estimate?=?-0.40%, p?25-75% (?_estimate?=?-1.46%, p?ConclusionsPhysical activity in urban children appeared associated with lower FOXP3 promoter methylation, a possible indicator of greater Treg function, under conditions of high BC exposure. Reduced FOXP3 promoter methylation was associated with higher lung function. These findings suggest that physical activity may induce immunologic benefits, particularly for urban children with greater risk of impaired lung function due to exposure to higher air pollution. FOXP3 promoter buccal cell methylation may function as a useful biomarker of that benefit.

SUBMITTER: Lovinsky-Desir S

PROVIDER: S-EPMC5470266 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Physical activity, black carbon exposure, and DNA methylation in the <i>FOXP3</i> promoter.

Lovinsky-Desir Stephanie S Jung Kyung Hwa KH Jezioro Jacqueline R JR Torrone David Z DZ de Planell-Saguer Mariangels M Yan Beizhan B Perera Frederica P FP Rundle Andrew G AG Perzanowski Matthew S MS Chillrud Steven N SN Miller Rachel L RL

Clinical epigenetics 20170613

<h4>Background</h4>Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead ...[more]

PMID: 28630656

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Project description:OBJECTIVE:Regular physical activity can improve cardiopulmonary health; however, increased respiratory rates and tidal volumes during activity may increase the effective internal dose of air pollution exposure. Our objective was to investigate the impact of black carbon (BC) measured by personal sampler on the relationship between physical activity and fractional exhaled nitric oxide (FeNO), a marker of airway inflammation. We hypothesized that higher personal BC would attenuate the protective effect of physical activity on airway inflammation. METHODS:We performed a cross-sectional study nested in a birth cohort of African American and Dominican children living in the Bronx and Northern Manhattan, New York City. Children were recruited based on age (target 9-14 year olds) and presence (n=70) or absence (n=59) of current asthma. Children wore wrist mounted accelerometers for 6 days and were classified as 'active' if they had ?60min of moderate-to-vigorous activity (MVA) each day and 'non-active' if they had <60min of MVA on any given day, based on CDC guidelines. Personal BC measured using a MicroAeth, was assessed during two 24-h periods, at the beginning and end of physical activity assessment. High BC was defined as the upper tertile of BC measured with personal sampler. FeNO measurements were sampled at the beginning and end of the of physical activity assessment. RESULTS:In multivariable linear regression models, 'active' children had 25% higher personal BC concentrations (p=0.02) and 20% lower FeNO (p=0.04) compared to 'non-active' children. Among children with high personal BC (n=33), there was no relationship between activity and FeNO (p=1.00). The significant protective relationship between activity and airway inflammation was largely driven by children with lower personal BC (n=96, p=0.04). CONCLUSIONS:Children that live in an urban environment and are physically active on a daily basis have higher personal exposure to BC. High BC offsets the protective relationship between physical activity and airway inflammation.