Gene expression profiles reveal distinct immunological responses of cobalt and cerium dioxide nanoparticles in two in vitro lung epithelial cell models

Toxicol Lett. 2014 Aug 4;228(3):157-69. doi: 10.1016/j.toxlet.2014.05.006. Epub 2014 May 10.

Abstract

Fragmentary knowledge exists on cellular signaling responses underlying possible adverse health effects of CoO- and CeO2-nanoparticles (NP)s after inhalation. We aimed to perform a time kinetic study of gene expression profiles induced by these NPs in alveolar A549 and bronchial BEAS-2B epithelial cells, and investigated possible immune system modulation. The kinetics of the cell responses induced by the NPs were different between the lung epithelial models. Both CoO- and CeO2-NP exposure induced mainly downregulation of gene transcription. BEAS-2B cells were found to be more sensitive, as they showed a higher number of differentially expressed transcripts (DET) at a 10-fold lower NP-concentration than A549 cells. Hierarchical clustering of all DET indicated that the transcriptional responses were heterogeneous among the two cell types and two NPs. Between 1% and 14% DET encoding markers involved in immune processes were observed. The transcriptional impact of the metal oxide NPs appeared to be cell-dependent, both at the general and immune response level, whereas each lung epithelial cell model responded differently to the two NP types. Thus, the study provides gene expression markers and immune processes involved in CoO- and CeO2-NP-induced toxicity, and demonstrates the usefulness of comprehensive-omics studies to differentiate between NP responses.

Keywords: A549; BEAS-2B; Cerium dioxide; Cobalt oxide; Nanoparticles; Transcriptomics.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cerium / toxicity*
  • Cluster Analysis
  • Cobalt / toxicity*
  • Computational Biology
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Epithelial Cells / pathology
  • Gene Expression Profiling* / methods
  • Gene Expression Regulation
  • Humans
  • Kinetics
  • Lung / drug effects*
  • Lung / immunology
  • Lung / pathology
  • Metal Nanoparticles*
  • Oligonucleotide Array Sequence Analysis
  • Oxides / toxicity*
  • Transcription, Genetic / drug effects

Substances

  • Oxides
  • Cerium
  • Cobalt
  • ceric oxide
  • cobalt oxide