Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke

Joong Won Lee, Zeina Jaffar, Kent E Pinkerton, Virginia Porter, Britten Postma, Maria Ferrini, Andrij Holian, Kevan Roberts, Yoon Hee Cho

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Growing evidence indicates that prenatal exposure to maternal smoking is a risk factor for the development of asthma in children. However, the effects of prenatal environmental tobacco smoke (ETS) exposure on the genome and lung immune cells are unclear. This study aims to determine whether in utero ETS exposure alters DNA methylation patterns and increases airway hyperreactivity (AHR) and inflammation. Pregnant C57BL/6 mice were exposed daily to a concentration of 1.0 mg/m3 ETS. AHR was determined in the 6-week-old offspring by measurement of airway resistance. Global and gene promoter methylation levels in lung DNA from offspring were analyzed by luminometric methylation and pyrosequencing assays, respectively. Offspring exposed to ETS showed a marked increase in the number of alveolar macrophages in the bronchoalveolar lavage fluid and level of IL-13 in the airways compared with offspring of filtered-Air exposed dams (controls). ETS exposure significantly augmented AHR compared with controls. In the methylation analysis, ETS-exposed offspring had a significantly lower level of global DNA methylation than the controls. We observed a significant increase in IFN-γ, and significant decrease in IL-13 methylation levels in the ETS group compared with controls. Collectively, these data suggest that in utero ETS exposure increases the risk of pulmonary inflammation and AHR through altered DNA methylation, but additional studies are needed to fully determine the causal link between changes in methylation and cytokines levels, as well as AHR.

Original languageEnglish (US)
Pages (from-to)724-730
Number of pages7
JournalInhalation Toxicology
Volume27
Issue number13
DOIs
StatePublished - Nov 10 2015

Fingerprint

Tobacco
Environmental Exposure
DNA Methylation
Smoke
Methylation
Interleukin-13
Genes
Maternal Exposure
Lung
Airway Resistance
Bronchoalveolar Lavage Fluid
Alveolar Macrophages
Inbred C57BL Mouse
Dams
Assays
Pneumonia
Asthma
Smoking
Air
Genome

Keywords

  • Airway hyperreactivity
  • DNA promoter methylation
  • environmental tobacco smoke
  • genomic methylation
  • inflammation

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke. / Lee, Joong Won; Jaffar, Zeina; Pinkerton, Kent E; Porter, Virginia; Postma, Britten; Ferrini, Maria; Holian, Andrij; Roberts, Kevan; Cho, Yoon Hee.

In: Inhalation Toxicology, Vol. 27, No. 13, 10.11.2015, p. 724-730.

Research output: Contribution to journalArticle

Lee, Joong Won ; Jaffar, Zeina ; Pinkerton, Kent E ; Porter, Virginia ; Postma, Britten ; Ferrini, Maria ; Holian, Andrij ; Roberts, Kevan ; Cho, Yoon Hee. / Alterations in DNA methylation and airway hyperreactivity in response to in utero exposure to environmental tobacco smoke. In: Inhalation Toxicology. 2015 ; Vol. 27, No. 13. pp. 724-730.
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