Nrf2 is closely related to allergic 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

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25 Citations (Scopus)

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, 5days/week, for a maximum of 8weeks. After exposure to DEP for 5weeks, 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.

Original languageEnglish
Pages (from-to)234-241
Number of pages8
JournalClinical Immunology
Volume137
Issue number2
DOIs
Publication statusPublished - 2010 Nov 1
Externally publishedYes

Keywords

  • Allergic airway inflammation
  • Anti-oxidant stress
  • Low-dose diesel exhaust particles
  • Nrf2-knockout mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Li, Y. J., Takizawa, H., Azuma, A., Kohyama, T., Yamauchi, Y., Takahashi, S., Yamamoto, M., Kawada, T., Kudoh, S., & Sugawara, I. (2010). Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice. Clinical Immunology, 137(2), 234-241. https://doi.org/10.1016/j.clim.2010.07.014