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...
Main Authors: | , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-10-01
|
Series: | Biomedicines |
Subjects: | |
Online Access: | https://www.mdpi.com/2227-9059/8/10/443 |
_version_ | 1797550234116554752 |
---|---|
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. |
first_indexed | 2024-03-10T15:26:34Z |
format | Article |
id | doaj.art-682c858f519a442ea950725793e6f5d3 |
institution | Directory Open Access Journal |
issn | 2227-9059 |
language | English |
last_indexed | 2024-03-10T15:26:34Z |
publishDate | 2020-10-01 |
publisher | MDPI AG |
record_format | Article |
series | Biomedicines |
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 |
work_keys_str_mv | AT yingjili nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT takakoshimizu nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT yusukeshinkai nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT tomomiihara nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT masaosugamata nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT katsuhitokato nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT maikokobayashi nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT yukiyohirata nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT hirofumiinagaki nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT makotouzuki nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT toshioakimoto nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT masakazuumezawa nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT kentakeda nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT arataazuma nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT masayukiyamamoto nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice AT tomoyukikawada nrf2lowerstheriskoflunginjuryviamodulatingtheairwayinnateimmuneresponseinducedbydieselexhaustinmice |