Nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice

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

doi:10.3390/biomedicines8100443

Nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice

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

Tohoku Medical Megabank Organization (ToMMo)

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2^+/+ and Nrf2^−/− 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 Nrf2^−/− mice compared with Nrf2^+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2^+/+ mice and mild suppression of the level of TNF-α in Nrf2^−/− mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2^−/− mice than in Nrf2^+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2^−/− mice than in Nrf2^+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2^−/− mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2^+/+ mice than in Nrf2^−/− 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.

Original language	English
Article number	443
Pages (from-to)	1-16
Number of pages	16
Journal	Biomedicines
Volume	8
Issue number	10
DOIs	https://doi.org/10.3390/biomedicines8100443
Publication status	Published - 2020 Oct

Keywords

Immune response
Lung diseases
Macrophage
Neutrophils
Oxidative stress/anti-oxidative stress

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10.3390/biomedicines8100443

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Li, Y. J., Shimizu, T., Shinkai, Y., Ihara, T., Sugamata, M., Kato, K., Kobayashi, M., Hirata, Y., Inagaki, H., Uzuki, M., Akimoto, T., Umezawa, M., Takeda, K., Azuma, A., Yamamoto, M., & Kawada, T. (2020). Nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice. Biomedicines, 8(10), 1-16. Article 443. https://doi.org/10.3390/biomedicines8100443

@article{14903a727ff144dba57d383c5f97403f,

title = "Nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice",

abstract = "In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2+/+ and Nrf2−/− 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 Nrf2−/− mice compared with Nrf2+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2+/+ mice and mild suppression of the level of TNF-α in Nrf2−/− mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2−/− mice than in Nrf2+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2−/− mice than in Nrf2+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2−/− mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2+/+ mice than in Nrf2−/− 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.",

keywords = "Immune response, Lung diseases, Macrophage, Neutrophils, Oxidative stress/anti-oxidative stress",

author = "Li, {Ying Ji} and Takako Shimizu and Yusuke Shinkai and Tomomi Ihara and Masao Sugamata and Katsuhito Kato and Maiko Kobayashi and Yukiyo Hirata and Hirofumi Inagaki and Makoto Uzuki and Toshio Akimoto and Masakazu Umezawa and Ken Takeda and Arata Azuma and Masayuki Yamamoto and Tomoyuki Kawada",

note = "Funding Information: This work was supported by a Grant-in-Aid for Scientific Research (No. 21590668) from the Ministry of Education, Culture, Sports, Science & Technology (MEXT) of Japan, and the Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science of Japan. We are grateful to all of our research collaborators of this work, especially Isamu Sugawara (Research Institute of Tuberculosis), Hiroshi Terada (Tokyo University of Science) for their cooperation; and Shoji Kudoh (Anti-Tuberculosis Association), Hajime Takizawa (Kyorin University) for their critical comments. Funding Information: Funding: This work was supported by a Grant-in-Aid for Scientific Research (No. 21590668) from the Ministry of Education, Culture, Sports, Science & Technology (MEXT) of Japan, and the Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science of Japan. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = oct,

doi = "10.3390/biomedicines8100443",

language = "English",

volume = "8",

pages = "1--16",

journal = "Biomedicines",

issn = "2227-9059",

publisher = "MDPI AG",

number = "10",

}

Li, YJ, Shimizu, T, Shinkai, Y, Ihara, T, Sugamata, M, Kato, K, Kobayashi, M, Hirata, Y, Inagaki, H, Uzuki, M, Akimoto, T, Umezawa, M, Takeda, K, Azuma, A, Yamamoto, M & Kawada, T 2020, 'Nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice', Biomedicines, vol. 8, no. 10, 443, pp. 1-16. https://doi.org/10.3390/biomedicines8100443

TY - JOUR

T1 - Nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice

AU - Li, Ying Ji

AU - Shimizu, Takako

AU - Shinkai, Yusuke

AU - Ihara, Tomomi

AU - Sugamata, Masao

AU - Kato, Katsuhito

AU - Kobayashi, Maiko

AU - Hirata, Yukiyo

AU - Inagaki, Hirofumi

AU - Uzuki, Makoto

AU - Akimoto, Toshio

AU - Umezawa, Masakazu

AU - Takeda, Ken

AU - Azuma, Arata

AU - Yamamoto, Masayuki

AU - Kawada, Tomoyuki

N1 - Funding Information: This work was supported by a Grant-in-Aid for Scientific Research (No. 21590668) from the Ministry of Education, Culture, Sports, Science & Technology (MEXT) of Japan, and the Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science of Japan. We are grateful to all of our research collaborators of this work, especially Isamu Sugawara (Research Institute of Tuberculosis), Hiroshi Terada (Tokyo University of Science) for their cooperation; and Shoji Kudoh (Anti-Tuberculosis Association), Hajime Takizawa (Kyorin University) for their critical comments. Funding Information: Funding: This work was supported by a Grant-in-Aid for Scientific Research (No. 21590668) from the Ministry of Education, Culture, Sports, Science & Technology (MEXT) of Japan, and the Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science of Japan. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/10

Y1 - 2020/10

N2 - In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2+/+ and Nrf2−/− 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 Nrf2−/− mice compared with Nrf2+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2+/+ mice and mild suppression of the level of TNF-α in Nrf2−/− mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2−/− mice than in Nrf2+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2−/− mice than in Nrf2+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2−/− mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2+/+ mice than in Nrf2−/− 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.

AB - In the present study, we investigated the role of Nrf2 in airway immune responses induced by diesel exhaust (DE) inhalation in mice. C57BL/6J Nrf2+/+ and Nrf2−/− 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 Nrf2−/− mice compared with Nrf2+/+ mice; however, the lack of an increase in the level of tumor necrosis factor (TNF)-α in the lung tissue in Nrf2+/+ mice and mild suppression of the level of TNF-α in Nrf2−/− mice were observed; the level of granulocyte macrophage colony-stimulating factor (GM-CSF) in the lung tissue decreased in Nrf2−/− mice than in Nrf2+/+ mice; the number of DE particle-laden alveolar macrophages in BALF were larger in Nrf2−/− mice than in Nrf2+/+ mice. The results of electron microscope observations showed alveolar type II cell injury and degeneration of the lamellar body after DE exposure in Nrf2−/− mice. Antioxidant enzyme NAD(P)H quinone dehydrogenase (NQO)1 mRNA expression level was higher in Nrf2+/+ mice than in Nrf2−/− 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.

KW - Immune response

KW - Lung diseases

KW - Macrophage

KW - Neutrophils

KW - Oxidative stress/anti-oxidative stress

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U2 - 10.3390/biomedicines8100443

DO - 10.3390/biomedicines8100443

M3 - Article

AN - SCOPUS:85094129074

SN - 2227-9059

VL - 8

SP - 1

EP - 16

JO - Biomedicines

JF - Biomedicines

IS - 10

M1 - 443

ER -

Nrf2 lowers the risk of lung injury via modulating the airway innate immune response induced by diesel exhaust in mice

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