Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice

Clin Immunol. 2008 Sep;128(3):366-73. doi: 10.1016/j.clim.2008.05.005. Epub 2008 Jul 9.

Abstract

To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative stress and host antioxidant responses play a key role in the development of DEP-induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose DEP for 7 h/day, 5 days/week, for 8 weeks. Nrf2(-/-) mice exposed to low-dose DEP showed significantly increased airway hyperresponsiveness and counts of lymphocytes and eosinophils, together with increased concentrations of IL-12 and IL-13, and thymus and activation-regulated chemokine (TARC), in BAL fluid than wild-type mice. In contrast, expression of antioxidant enzyme genes was significantly higher in wild-type mice than in Nrf2(-/-) mice. We have first demonstrated that disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by inhalation of low-dose DEP in mice. These results strongly suggest that DEP-induced oxidative stress and host antioxidant responses play some role in the development of DEP-induced airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Bronchial Hyperreactivity / etiology*
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / metabolism
  • Bronchial Hyperreactivity / pathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / analysis
  • Disease Susceptibility*
  • Enzyme Induction
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inhalation Exposure
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress
  • Respiratory System / immunology
  • Respiratory System / metabolism
  • Vehicle Emissions / toxicity*

Substances

  • Antioxidants
  • Cytokines
  • Immunoglobulin G
  • NF-E2-Related Factor 2
  • Vehicle Emissions
  • Immunoglobulin E