Academic journal article Environmental Health Perspectives

Maternal Exposure to Polycyclic Aromatic Hydrocarbons and 5'-CpG Methylation of Interferon-[Gamma] in Cord White Blood Cells

Academic journal article Environmental Health Perspectives

Maternal Exposure to Polycyclic Aromatic Hydrocarbons and 5'-CpG Methylation of Interferon-[Gamma] in Cord White Blood Cells

Article excerpt

BACKGROUND: Maternal factors are implicated in the onset of childhood asthma. Differentiation of naive CD4+ T lymphocytes into pro-allergic T-helper 2 cells induces interleukin (IL)4 expression and inhibits interferon (IFN)[gamma] 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 IFN[gamma] and IL4.

METHODS: We assessed the effects of benzo[a]pyrene (BaP), a representative airborne PAH, on the methylation status of the IFN[gamma] and IL4 promoters in Jurkat cells and two lung adenocarcinoma cell lines, and on gene expression. In addition, we evaluated methylation status of the IFN[gamma] 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 IFN[gamma], but not IL4. IFN[gamma] 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 IFN[gamma] in cord blood DNA from cohort children. These findings support a potential role of epigenetics in fetal reprogramming by PAH-induced environmental diseases.

KEY WORDS: cord white blood cell, cytokines, DNA methylation, epigenetic epidemiology, epigenetics, fetal origins of disease, interferon-[gamma], interleukin 4. Environ Health Perspect 120:1195-1200 (2012). [Online 4 May 2012]

The dysregulation of specific T lymphocytes and their cytokines plays an important role in the etiology of allergic asthma (Ray et al. 2010). The onset of allergic asthma is characterized by increased infiltration of naive [CD4.sup.+] T lymphocytes into the bronchial mucosa. Upon sensitization by allergens, activated dendritic cells initiate the differentiation of nave [CD4.sup.+] T cells into proallergic T-helper (Th) 2 cells instead of the counterregulatory Th1 cells (Hammad and Lambrecht 2006). The progressive increase in the commitment of [CD4.sup.+] T cells toward a Th2 phenotype is accompanied by an upregulation of Th2 cytokines, such as interleukin (IL) 4, and the silencing of Th1 cytokines like interferon (IFN) [gamma] (Ray et al. 2010).

Allergic asthma has been hypothesized to be a disorder of fetal origin that is influenced greatly by maternal factors (Ho 2010). However, molecular mechanisms underlying the potential effects of maternal exposures on asthma remain unclear. We are currently studying a cohort of African-American and Dominican children living in a traffic-laden area of Northern Manhattan and South Bronx, New York, where asthma prevalence greatly exceeds national rates (Centers for Disease Control and Prevention 2011). Prenatal exposure to traffic-derived pollutants, such as polycyclic aromatic hydrocarbons (PAHs), may account for some of the increased asthma prevalence in this cohort (Tonne a al. 2004). We previously analyzed DNA isolated from umbilical cord white blood cells (UCWBCs) in a subset of cohort children and identified six genes whose methylation status was associated with maternal PAH exposure using a methylation-sensitive restriction fingerprinting approach (Perera a al. 2009). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the promoter methylation in UCWBC DNA and the level of gene expression in matched fetal placental tissues. …

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