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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article number443
Pages (from-to)1-16
Number of pages16
JournalBiomedicines
Volume8
Issue number10
DOIs
Publication statusPublished - 2020 Oct
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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