1. Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice
- Author
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Li, Ying Ji, Takizawa, Hajime, Azuma, Arata, Kohyama, Tadashi, Yamauchi, Yasuhiro, Takahashi, Satoru, Yamamoto, Masayuki, Kawada, Tomoyuki, Kudoh, Shoji, and Sugawara, Isamu
- Subjects
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TRANSCRIPTION factors , *LABORATORY mice , *DIESEL motor exhaust gas , *ANTIOXIDANTS , *EOSINOPHILS , *CYTOKINES , *OXIDATIVE stress , *LYMPHOCYTES , *CLINICAL immunology - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2008
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