Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice

Clin Immunol. 2010 Nov;137(2):234-41. doi: 10.1016/j.clim.2010.07.014. Epub 2010 Aug 24.

Abstract

We have recently reported that disruption of nuclear erythroid 2 P45-related factor 2 (Nrf2) enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles (DEP) in mice. C57BL/6 Nrf2 knockout (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) mice were further exposed to low-dose DEP for 7h/day, 5 days/week, for a maximum of 8 weeks. After exposure to DEP for 5 weeks, allergic airway inflammation was generated in the mice by intraperitoneal sensitization with OVA followed by intranasal challenge. Nrf2(-/-) mice exposed to relatively low-dose DEP showed significantly increased percentage changes relative to the OVA alone group in terms of airway hyperresponsiveness (AHR) and inflammatory cells, levels of IL-5 and thymus and activation regulated chemokine (TARC) in bronchoalveolar lavage (BAL) fluid than did Nrf2(+/+) mice. Lung tissues of Nrf2(-/-) mice after DEP exposure showed inflammatory cell infiltrates, and increased PAS staining-positive mucus cell hyperplasia. In contrast, the percentage changes relative to the OVA group in the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in whole blood was higher in Nrf2(+/+) mice than in Nrf2(-/-) mice. By using Nrf2(-/-) mice, it was shown for the first time that relatively low-dose DEP exposure induces oxidant stress, and that host anti-oxidant responses play a key role in the development of DEP-induced exacerbation of allergic airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchial Hyperreactivity / physiopathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Glutathione / blood
  • Glutathione Disulfide / blood
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Leukocytes / pathology
  • Lung / pathology
  • Lung / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / deficiency
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Ovalbumin / immunology
  • Respiratory Hypersensitivity / chemically induced
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology
  • Respiratory Hypersensitivity / physiopathology
  • Vehicle Emissions / toxicity*

Substances

  • Chemokines
  • Cytokines
  • Immunoglobulin G
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Vehicle Emissions
  • Immunoglobulin E
  • Ovalbumin
  • Glutathione
  • Glutathione Disulfide