Abstract
Allergic rhinitis (AR) is a chronic inflammatory disorder driven by T cell activation. How particulate matter contributes to epigenetic changes that in turn influence cytokine gene expression in CD4+T cells remains unclear. In this study, 105 children diagnosed with AR and 90 healthy controls were recruited to explore the possible mechanism of particulate matter (PM) on the epigenetic regulation of CD4+T IFN-γ and IL-4 promoter genes. Daily average PM10 and PM2.5 were obtained from five state-controlled monitoring stations, and activity-based dynamic exposure and personal exposure data were collected. DNA methylation patterns of IFN-γ and IL-4 promoter regions were analyzed using bisulfite sequencing. mRNA levels were detected by real-time quantitative reverse transcription polymerase chain reaction. We found that the methylation rate in IFN-γ was higher in AR CD4+T cells than in the controls. IFN-γ mRNA expression was significantly decreased in CD4+T cells, and negatively correlated with the mean methylation level of IFN-γ. However, no correlation between IL-4 methylation and IL-4 mRNA expression was found. After adjusting for age, gender, exclusive breastfeeding within 4 months after birth and parental history of allergic disease, out data showed that PM2.5 exposure level was positively correlated with methylation level in IFN-γ promoter region and decreased cytokine expression. We conclude that the effect of PM2.5 on pediatric AR may be mediated through epigenetic modification of IFN-γ promoter region.
Highlights
The prevalence of allergic diseases, such as allergic rhinitis (AR) in children appears to be increasing globally, including in China
After adjusting for age, gender, exclusive breastfeeding within 4 months after birth and parental history of allergic disease, out data showed that PM2.5 exposure level was positively correlated with methylation level in IFN-γ promoter region and decreased cytokine expression
Exposure to PM2.5 in Allergic rhinitis (AR) children was significantly associated with the methylation level of the promoter region in IFN-γ after the adjustment for exclusive breastfeeding within 4 months after birth and parental history of allergic disease, which showed significant difference between the AR and the control www.oncotarget.com (β = 1.441, SE = 0.672, p = 0.039)
Summary
The prevalence of allergic diseases, such as allergic rhinitis (AR) in children appears to be increasing globally, including in China. The etiology of AR remains uncertain, there is evidence suggesting that the allergic response is associated with certain ambient air pollutant exposure [2]. Ambient particulate matter (PM) pollution is one of the most serious environmental challenges in China, with an important impact on human health, especially in children and other susceptible populations. The adverse health effects associated with air pollution exposure may be attributed to short-term (a few minutes to one day) or long-term (a few months to a few decades) exposure, and different pollutants may have widely different exposure-response characteristics [3]. A number of epidemiological studies have found that exposure to air pollution could generate a variety of negative health effects, including increased frequency and severity of AR, especially AR combined with asthma [6, 7]
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