Maternal exposure to polycyclic aromatic hydrocarbons and 5'-CpG methylation of interferon-γ in cord white blood cells

Wan Yee Tang, Linda Levin, Glenn Talaska, Yuk Yin Cheung, Julie Herbstman, Deliang Tang, Rachel L. Miller, Frederica Perera, Shuk Mei Ho

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1195-1200
Number of pages6
JournalEnvironmental health perspectives
Volume120
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Cord white blood cell
  • Cytokines
  • DNA methylation
  • Epigenetic epidemiology
  • Epigenetics
  • Fetal origins of disease
  • Interferon-γ
  • Interleukin 4

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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