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
Affiliations
Ying-Ji Li
Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, Japan
Takako Shimizu
Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, Japan
Yusuke Shinkai
Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan
Tomomi Ihara
Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan
Masao Sugamata
Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan
Katsuhito Kato
Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, Japan
Maiko Kobayashi
Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, Japan
Yukiyo Hirata
Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, Japan
Hirofumi Inagaki
Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, Japan
Makoto Uzuki
Division of Laboratory Animal Science, Nippon Medical School, Tokyo 113-0031, Japan
Toshio Akimoto
Division of Laboratory Animal Science, Nippon Medical School, Tokyo 113-0031, Japan
Masakazu Umezawa
Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan
Ken Takeda
Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan
Arata Azuma
Department of Pulmonary Medicine and Oncology, Nippon Medical School, Tokyo 113-8602, Japan
Masayuki Yamamoto
Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Tomoyuki Kawada
Department of Hygiene and Public Health, Nippon Medical School, 1-25-16 Nezu, Bunkyo-ku, Tokyo 113-0031, Japan
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.
