Maternal Exposure to Polycyclic Aromatic Hydrocarbons and 5’-CpG Methylation of Interferon-γ in Cord White Blood Cells

Abstract

Background: Maternal factors are implicated in the onset of childhood asthma. Differentiation of naïve CD4+ T lymphocytes into pro-allergic T-helper 2 cells induces interleukin (IL)4 expression and inhibits interferon (IFN)γ expression accompanied by concordant methylation changes in the promoters of these genes. However, it has yet to be established whether maternal exposure to polycyclic aromatic hydrocarbons (PAHs) can alter these gene promoters epigenetically during fetal development.Objectives: In this study we sought to elucidate the relationship between maternal PAH exposure and promoter methylation status of IFNγ and IL4.Methods: We assessed the effects of benzo[a]pyrene (BaP), a representative airborne PAH, on the methylation status of the IFNγ and IL4 promoters in Jurkat cells and two lung adenocarcinoma cell lines, and on gene expression. In addition, we evaluated methylation status of the IFNγ promoter in cord white blood cells from 53 participants in the Columbia Center for Children’s Environmental Health cohort. Maternal PAH exposure was estimated by personal air monitoring during pregnancy.Results: In vitro exposure of the cell models to low, noncytotoxic doses (0.1 and 1 nM) of BaP elicited increased promoter hypermethylation and reduced expression of IFNγ, but not IL4. IFNγ promoter methylation in cord white blood cells was associated with maternal PAH exposure in the cohort study subsample.Conclusion: Consistent with the results for the cell lines, maternal exposure to PAHs was associated with hypermethylation of IFNγ in cord blood DNA from cohort children. These findings support a potential role of epigenetics in fetal reprogramming by PAH-induced environmental diseases.

Epigenetic Alterations by DNA Methylation in House Dust Mite–Induced Airway Hyperresponsiveness

“…No statistically significant changes were found in average methylation percent of all CGs among the akt1 s1, acsl3, and tm6 sf promoters. It is known that DNA methylation of a single CG (or very few) can alter gene transcription (19). Therefore, it was necessary to assess the methylation status at individual CG sites.…”

“…This phenomenon is linked to gene activation, gene silencing, and chromosomal instability without alterations in DNA sequences. Compared to histone modifications or noncoding RNA silencing, DNA methylation studies are commonly demonstrated in both clinical studies and experimental models of lung diseases (9)(10)(11)(17)(18)(19). DNA methylation refers to the covalent addition of a methyl group derived from S-adenosyl-L-methionine to the fifth carbon of the cytosine ring to form the fifth base, 5-methyl cytosine (12).…”

Chronic Exposure to Water Pollutant Trichloroethylene Increased Epigenetic Drift in CD4 + T cells

“…It has been reported that DNA methylation in a relatively small region of the Ifng promoter (that includes the -53, -205 and -297 CpG sites) controls promoter-driven Ifng expression during CD4 + T-cell differentiation [42,44]. In addition to the cytokines secreted during Th2 cell differentiation, certain environmental events such as adult exposure to diesel exhaust or developmental exposure to polycyclic aromatic hydrocarbons can alter epigenetic marks in the Ifng promoter [25,45,46]. Low to moderate levels of methylation on the Ifng promoter such as we report here following TCE exposure may allow the gene to remain 'poised' for varying levels of transcription without being silenced.…”

The Neonatal Methylome as a Gatekeeper in the Trajectory to Childhood Asthma

“…Diesel exhaust Air pollution, and more specifically diesel exhaust particles, are known to be associated with both risk for asthma and allergy [44] and changes in DNA methylation profiles [45][46][47]. Recent work assessed how in vivo exposure to diesel exhaust (through a dedicated apparatus) and allergen (through challenge within the lung) affects DNA methylation in human epithelial cells obtained by bronchoscopy.…”