Ozone-induced disruptions of lung transcriptomes

Kishorchandra Gohil, Carroll E Cross, Jerold A Last

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

We have analyzed changes in ∼4000 lung mRNAs, with GeneChips, in mice exposed to 1ppm O3 for three consecutive nights (8h per night). Differential gene expression analysis identified ∼260 O3 sensitive genes; ∼80% of these were repressed and ∼20% were induced in O3-exposed mice compared to the air-exposed controls. A 20-fold induction of serum amyloid A3 mRNA by O3 suggested activation of NF-κB and CCAAT/enhancer binding protein-mediated pathways by inflammatory cytokines. Induction (up to 14-fold) of 12 genes that increase DNA synthesis and cell cycle progression, and increase (∼7-fold) in CD44 mRNA and macrophage metalloelastase suggested a state of O3-induced hyperplasia and lung remodeling. Several mRNAs encoding enzymes of xenobiotic metabolism and cytoskeletal functions were repressed and may suggest cytokine mediated suppression of cytochrome P450 expression and cachexia-like inflammatory state in ozone-exposed lungs. The expressions of ∼30 genes of immune response were also repressed. Collectively this genome-wide analysis of lungs identified ozone-induced disruption of gene transcriptional profile indicative of increased cellular proliferation under suppressed immune surveillance and xenobiotic metabolism.

Original languageEnglish (US)
Pages (from-to)719-728
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume305
Issue number3
DOIs
StatePublished - Jun 6 2003

Keywords

  • Cachexia
  • Cell cycle
  • Immune response
  • MHC
  • Oligonucleotide arrays
  • Transcription factors

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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