Epigenetic Changes in Alveolar Type II Lung Cells of A/J Mice Following Intranasal Treatment with Lipopolysaccharide

Christopher L. Seiler, Jung Min Song, Jenna Fernandez, Juan E. Abrahante, Thomas J.Y. Kono, Yue Chen, Yanan Ren, Fekadu Kassie, Natalia Y. Tretyakova

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Lipopolysaccharide (LPS) is a bacterial endotoxin present in cigarette smoke. LPS is known to induce inflammation and to increase the size and the multiplicity of lung tumors induced by tobacco-specific nitrosamines. However, the means by which LPS contributes to pulmonary carcinogenesis are not known. One possible mechanism includes LPS-mediated epigenetic deregulation, which leads to aberrant expression of genes involved in DNA repair, tumor suppression, cell cycle progression, and cell growth. In the present work, epigenetic effects of LPS were examined in alveolar type II lung cells of A/J mice. Type II cells were selected because they serve as progenitors of lung adenocarcinomas in smoking induced lung cancer. A/J mice were intranasally treated with LPS, followed by isolation of alveolar type II cells from the lung using cell panning. Global levels of DNA methylation and histone acetylation were quantified by mass spectrometry, while genome-wide transcriptomic changes were characterized by RNA-Seq. LPS treatment was associated with epigenetic changes including decreased cytosine formylation and reduced histone H3K14 and H3K23 acetylation, as well as altered expression levels of genes involved in cell adhesion, inflammation, immune response, and epigenetic regulation. These results suggest that exposure to inflammatory agents in cigarette smoke leads to early epigenetic changes in the lung, which may collaborate with genetic changes to drive the development of lung cancer.

Original languageEnglish (US)
Pages (from-to)831-839
Number of pages9
JournalChemical research in toxicology
Issue number5
StatePublished - May 20 2019

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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