Linking oxidative events to inflammatory and adaptive gene expression induced by exposure to an organic particulate matter component

Environ Health Perspect. 2012 Feb;120(2):267-74. doi: 10.1289/ehp.1104055. Epub 2011 Oct 13.


Background: Toxicological studies have correlated inflammatory effects of diesel exhaust particles (DEP) with its organic constituents, such as the organic electrophile 1,2-naphthoquinone (1,2-NQ).

Objective: To elucidate the mechanisms involved in 1,2-NQ-induced inflammatory responses, we examined the role of oxidant stress in 1,2-NQ-induced expression of inflammatory and adaptive genes in a human airway epithelial cell line.

Methods: We measured cytosolic redox status and hydrogen peroxide (H2O2) in living cells using the genetically encoded green fluorescent protein (GFP)-based fluorescent indicators roGFP2 and HyPer, respectively. Expression of interleukin-8 (IL-8), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) mRNA was measured in BEAS-2B cells exposed to 1,2-NQ for 1-4 hr. Catalase overexpression and metabolic inhibitors were used to determine the role of redox changes and H2O2 in 1,2-NQ-induced gene expression.

Results: Cells expressing roGFP2 and HyPer showed a rapid loss of redox potential and an increase in H2O2 of mitochondrial origin following exposure to 1,2-NQ. Overexpression of catalase diminished the H2O2-dependent signal but not the 1,2-NQ-induced loss of reducing potential. Catalase overexpression and inhibitors of mitochondrial respiration diminished elevations in IL-8 and COX-2 induced by exposure to 1,2-NQ, but potentiated HO-1 mRNA levels in BEAS cells.

Conclusion: These data show that 1,2-NQ exposure induces mitochondrial production of H2O2 that mediates the expression of inflammatory genes, but not the concurrent loss of reducing redox potential in BEAS cells. 1,2-NQ exposure also causes marked expression of HO-1 that appears to be enhanced by suppression of H2O2. These findings shed light into the oxidant-dependent events that underlie cellular responses to environmental electrophiles.

MeSH terms

  • Air Pollutants / immunology
  • Air Pollutants / toxicity*
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Catalase / metabolism
  • Cell Line
  • Cyclooxygenase 2 / genetics
  • Environmental Health / methods
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects*
  • Green Fluorescent Proteins / metabolism
  • Heme Oxygenase-1 / genetics
  • Humans
  • Hydrogen Peroxide / metabolism
  • Inflammation*
  • Interleukin-8 / genetics
  • Naphthoquinones / immunology
  • Naphthoquinones / toxicity*
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Particulate Matter / immunology
  • Particulate Matter / toxicity
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Vehicle Emissions / toxicity


  • Air Pollutants
  • Interleukin-8
  • Naphthoquinones
  • Particulate Matter
  • RNA, Messenger
  • Reactive Oxygen Species
  • Vehicle Emissions
  • Green Fluorescent Proteins
  • 1,2-naphthoquinone
  • Hydrogen Peroxide
  • Catalase
  • Heme Oxygenase-1
  • Cyclooxygenase 2
  • PTGS2 protein, human