Pathogenesis of particulate matters and IL-4 DNA methylation in CD4+T cells in children with AR / 中国耳鼻咽喉头颈外科

ABSTRACT

OBJECTIVE To investigate the possible effects of meteorological and environmental factors on IL-4 gene specific DNA methylation levels in CD4+T cells of children with AR.METHODS Thirty five pediatric AR patients(6-12 years) followed up for one year from the Department of Otolaryngology, Shanghai Children Medical Center from Jan, 1, 2012 to Dec. 31, 2012 were included in this study. Data on daily particulate matter of diameter smaller than 10 micrometer(PM10) and particulate matter of diameter smaller than 2.5 micrometer(PM2.5) was available as average values derived from the data of 6 state-controlled monitoring stations distributed across Pudong District, Shanghai. We quantified IL-4(interleukin-4) gene specific DNA methylation levels in CD4+T cells from 35 patients with AR and 30 healthy controls. mRNA levels of IL-4 gene were measured by real-time reverse transcriptase-PCR. Methods of personal exposure assessment of PM2.5 and PM10 were measured.RESULTS Compared with controls, IL-4 promoter region was hypomethylated in AR CD4+T cells(P=0.038). Of all observed CpG sites in IL-4 promoter region, there was significant differences in CpG-48, CpG+54(P=0.041, 0.032). IL-4 mRNA expression was significantly increased in CD4+T cells(P=0.039). The level of IL-4 mRNA expression was negatively correlated to the mean level of methylation in IL-4 promoter region. After adjusting, level of PM10 exposure was negatively correlated with level of methylation in IL-4 promoter region(r2=0.419,β=-0.470,SD=0.781,P=0.045). CONCLUSION Level of methylation in IL-4 promoter region may be affected by PM10 exposure.