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

Ying Ji Li, Hajime Takizawa, Arata Azuma, Tadashi Kohyama, Yasuhiro Yamauchi, Satoru Takahashi, Masayuki Yamamoto, Tomoyuki Kawada, Shoji Kudoh, Isamu Sugawara

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)366-373
Number of pages8
JournalClinical Immunology
Volume128
Issue number3
DOIs
Publication statusPublished - 2008 Sep
Externally publishedYes

Keywords

  • Airway hyperresponsiveness
  • Cytokine
  • Diesel exhaust particle
  • Eosinophils
  • Mouse model
  • Nrf2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice'. Together they form a unique fingerprint.

Cite this