Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice

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...

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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/8/10/443
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author 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
author_facet 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
author_sort Ying-Ji Li
collection DOAJ
description 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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spelling doaj.art-682c858f519a442ea950725793e6f5d32023-11-20T17:58:38ZengMDPI AGBiomedicines2227-90592020-10-0181044310.3390/biomedicines8100443Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in MiceYing-Ji Li0Takako Shimizu1Yusuke Shinkai2Tomomi Ihara3Masao Sugamata4Katsuhito Kato5Maiko Kobayashi6Yukiyo Hirata7Hirofumi Inagaki8Makoto Uzuki9Toshio Akimoto10Masakazu Umezawa11Ken Takeda12Arata Azuma13Masayuki Yamamoto14Tomoyuki Kawada15Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, JapanDepartment of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, JapanCenter for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, JapanCenter for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, JapanCenter for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, JapanDepartment of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, JapanDepartment of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, JapanDepartment of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, JapanDepartment of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, JapanDivision of Laboratory Animal Science, Nippon Medical School, Tokyo 113-0031, JapanDivision of Laboratory Animal Science, Nippon Medical School, Tokyo 113-0031, JapanCenter for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, JapanCenter for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, JapanDepartment of Pulmonary Medicine and Oncology, Nippon Medical School, Tokyo 113-8602, JapanMedical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDepartment of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, JapanIn 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.https://www.mdpi.com/2227-9059/8/10/443oxidative stress/anti-oxidative stressimmune responsemacrophageneutrophilslung diseases
spellingShingle 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
Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice
Biomedicines
oxidative stress/anti-oxidative stress
immune response
macrophage
neutrophils
lung diseases
title Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice
title_full Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice
title_fullStr Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice
title_full_unstemmed Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice
title_short Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice
title_sort nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice
topic oxidative stress/anti-oxidative stress
immune response
macrophage
neutrophils
lung diseases
url https://www.mdpi.com/2227-9059/8/10/443
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