Integrated analysis of microRNA and mRNA expression profiles highlights aldehyde-induced inflammatory responses in cells relevant for lung toxicity

Toxicology. 2015 Aug 6;334:111-21. doi: 10.1016/j.tox.2015.06.007. Epub 2015 Jun 12.

Abstract

We have shown that aldehydes impact the bronchial airway gene expression associated with inflammatory responses. In this study, we sought to determine whether microRNA (miRNA) plays a role in regulating the airway gene expression response to aldehyde exposure. We analyzed the whole genome miRNA and mRNA expression profiles of human alveolar epithelial cells exposed to 3 aldehydes (propanal, butanal, and pentanal) to identify aldehyde-sensitive miRNAs and to characterize the relationships between miRNAs and the expression of candidate cytokine-related genes, which are activated in response to inflammatory signals. Microarray analysis identified 15 miRNAs for propanal, 25 miRNAs for butanal, and 10 miRNAs for pentanal, which were differentially expressed in A549 human alveolar epithelial cells compared with vehicle control samples. Integrated analyses of miRNA and mRNA expression profiles identified significant miRNA-mRNA correlations. Gene ontology (GO) analysis of putative target genes (443 genes for propanal, 2166 genes for butanal, and 364 genes for pentanal) showed that the biological category "cytokine-cytokine receptor interaction" was prominently annotated. Moreover, we detected increased levels of interleukin (IL)-6 and IL-8 released in the 3 aldehyde exposure groups. Through an integrated analysis of the miRNA and mRNA expression profiles of aldehydes, we provide evidence that aldehyde can affect cytokine-induced toxicity signaling. Therefore, this study demonstrates the added value of an integrated miRNA-mRNA approach for identifying molecular events altered by environmental pollutants in an in vitro human model.

Keywords: Aldehydes; Cytokine; Gene ontology (GO); Inflammation; Microarray; Target mRNAs; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / toxicity*
  • Cell Line, Tumor
  • Cytokines / genetics*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling* / methods
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks
  • Humans
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Pneumonia / chemically induced*
  • Pneumonia / genetics*
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Toxicogenetics* / methods

Substances

  • Aldehydes
  • Cytokines
  • MicroRNAs
  • RNA, Messenger
  • propionaldehyde
  • pentanal
  • butyraldehyde