Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice
2020
Ying-Ji Li | Takako Shimizu | Yusuke Shinkai | Tomomi Ihara | Masao Sugamata | Katsuhito Kato | Maiko Kobayashi | Yukiyo Hirata | Hirofumi Inagaki | Makoto Uzuki | Toshio Akimoto | Masakazu Umezawa | Ken Takeda | Arata Azuma | Masayuki Yamamoto | Tomoyuki Kawada
In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J <i>Nrf2</i><sup>+/+</sup> and <i>Nrf2</i><sup>−/−</sup> mice were exposed to DE or clean air for 8 h/day and 6 days/week for 4 weeks. After DE exposure, the number of neutrophils and macrophage inflammatory protein (MIP)-2 level in bronchoalveolar lavage fluid (BALF) and interleukin (IL)-17 level in the lung tissue increased in <i>Nrf2</i><sup>−/−</sup> mice compared with <i>Nrf2</i><sup>+/+</sup> mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in <i>Nrf2</i><sup>+/+</sup> mice and mild suppression of the level of TNF-α in <i>Nrf2</i><sup>−/−</sup> mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in <i>Nrf2</i><sup>−/−</sup> mice than in <i>Nrf2</i><sup>+/+</sup> mice; the number of DE particle-laden alveolar macrophages in BALF were larger in <i>Nrf2</i><sup>−/−</sup> mice than in <i>Nrf2</i><sup>+/+</sup> mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in <i>Nrf2</i><sup>−/−</sup> mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in <i>Nrf2</i><sup>+/+</sup> mice than in <i>Nrf2</i><sup>−/−</sup> mice after DE exposure. Our results suggested that Nrf2 reduces the risk of pulmonary disease via modulating the airway innate immune response caused by DE in mice.
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