Particulate matter exposure is associated with inflammatory gene methylation in obese subjects

Abstract

BackgroundOverweight and obesity are becoming more widespread with alarming projections for the coming years. Obesity may increase susceptibility to the adverse effects of PM exposure, exacerbating the effects on cardiovascular diseases and altering the biomarkers of vascular inflammation. The associated biological mechanisms have not been fully understood yet; the common denominator in the pathogenesis of the co-morbidities of obesity is the presence of an active, low-grade inflammatory process. DNA methylation has been shown to regulate inflammatory pathways that are responsible for the development of cardiovascular diseases.ObjectivesThe aim of the study was to investigate, in a population of overweight/obese subjects, the effects of PM on blood DNA methylation in genes associated to inflammatory response.MethodsUsing bisulfite pyrosequencing, we measured DNA methylation in peripheral blood mononuclear cells from 186 overweighted/obese subjects. In particular, we quantified DNA methylation in a set of 3 candidate genes, including CD14, TLR4 and TNF-α, because of the important roles that these genes play in the inflammatory pathway. Personal exposure to PM10 was estimated for each subject based on the local PM10 concentrations, measured by monitoring stations at residential address. Repeated measure models were used to evaluate the association of PM10 with each genes, accounting for possible correlations among the genes that regulate the same inflammatory pathway.ResultsWe found an inverse association between the daily PM10 exposure and the DNA methylation of inflammatory genes, measured in peripheral blood of healthy overweight/obese subjects. Considering different exposure time-windows, the effect on CD14 and TLR4 methylation was observed, respectively, in days 4–5-6, and days 6–7-8. TNF-α methylation was not associated to PM10.ConclusionsOur findings support a picture in which PM10 exposure and transcriptional regulation of inflammatory gene pathway in obese subjects are associated.

Possible Mediation by Methylation in Acute Inflammation Following Personal Exposure to Fine Particulate Air Pollution

“…Evidence also suggests effects on methylation specific to airway inflammation: nitric oxide synthase 2a methylation decreased within 24 hours of PM 2.5 exposure (22). Reduced methylation of inflammation genes.was also associated with acute or intermediate-term exposure to air pollutants (19,(21)(22)(23)(24)50).…”

Evaluation of DNA methylation of inflammatory genes following treatment of chronic periodontitis: A pilot case–control study

“…For each gene, CpG positions were selected based on previously published data (Dawsey et al., ; Madrigano et al., ; Cantone et al., ), as they are more consistent in terms of repeatability of the assay. Four CpG islands were analysed for COX‐2 and TNF‐ α genes while two were assessed for IFN‐ γ gene.…”

“…The CpG positions were selected according to data published in literature for the same assessed genes (Dawsey et al., ; Madrigano et al., ; Cantone et al., , which ensures consistency in terms of repeatability of the assay.…”

“…Analysis of DNA methylation was performed using previously published methods (Bollati et al, 2007;Tarantini et al, 2013) The CpG positions were selected according to data published in literature for the same assessed genes (Dawsey et al, 2008;Madrigano et al, 2012;Cantone et al, 2017), which ensures consistency in terms of repeatability of the assay.…”

Microtubule destabilization caused by particulate matter contributes to lung endothelial barrier dysfunction and inflammation

“…PM-induced mitochondrial reactive oxygen species (ROS) release plays a critical role in the development of these pathological cascades [8, 9]. Moreover, PM may also alter the expression of inflammatory molecules through complex pathways including DNA methylation-mediated epigenetic modification and changes in microRNAs expression [10–12]. …”