1. Nrf2 is closely related to allergic 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
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AIRWAY (Anatomy) , *ALLERGIES , *INFLAMMATION , *LABORATORY mice , *THYMUS , *CHEMOKINES , *DISEASE exacerbation , *ANTIOXIDANTS , *DIESEL motor exhaust gas , *PHYSIOLOGY - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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