title: Nrf2 Regulates the Risk of a Diesel Exhaust Inhalation-Induced Immune Response during Bleomycin Lung Injury and Fibrosis in Mice.
abstract: The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to bothNrf2+/+andNrf2-/-C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection. Inhalation of DE induced significant inhibition of airway clearance function and the proinflammatory cytokine secretion in macrophages, an increase in neutrophils, and severe lung inflammatory injury, which were greater inNrf2-/-mice than inNrf2+/+mice. In contrast, inhalation of DE was observed to induce a greater increase of hydroxyproline content in the lung tissues and significantly higher pulmonary antioxidant enzyme mRNA expression in theNrf2+/+mice than inNrf2-/-mice. DE is an important risk factor, and Nrf2 regulates the risk of a DE inhalation induced immune response during BLM lung injury and fibrosis in mice.
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, Tokyo 113-0031, Japan. li-yingji@nms.ac.jp.
authors.forename: Ying-Ji
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, Tokyo 113-0031, Japan. takako-s@nms.ac.jp.
authors.forename: Takako
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan. shinkai49@gmail.com.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Shinkai
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, Tokyo 113-0031, Japan. yuki-hir@nms.ac.jp.
authors.forename: Yukiyo
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, Tokyo 113-0031, Japan. hrfmi@nms.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Inagaki
authors.affiliation: The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan. takedak@rs.noda.tus.ac.jp.
authors.forename: Ken
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Pulmonary Medicine/Infection and Oncology, Nippon Medical School, Tokyo 113-8602, Japan. azuma_arata@yahoo.co.jp.
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. masiyamamoto@med.tohoku.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, Tokyo 113-0031, Japan. kawada@nms.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawada
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism*; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D055370:Lung Injury / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D016207:Cytokines; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D001335:Vehicle Emissions; D001761:Bleomycin; D006909:Hydroxyproline
keywords: Nrf2; bleomycin; diesel exhaust; lung injury and fibrosis; oxidative stress/antioxidative stress