title: Nrf2 is closely related to allergic airway inflammatory responses induced by low-dose diesel exhaust particles in mice.
abstract: We have recently reported that disruption of nuclear erythroid 2 P45-related factor 2 (Nrf2) enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles (DEP) in mice. C57BL/6 Nrf2 knockout (Nrf2(-/-)) mice and wild-type (Nrf2(+/+)) mice were further exposed to low-dose DEP for 7h/day, 5 days/week, for a maximum of 8 weeks. After exposure to DEP for 5 weeks, allergic airway inflammation was generated in the mice by intraperitoneal sensitization with OVA followed by intranasal challenge. Nrf2(-/-) mice exposed to relatively low-dose DEP showed significantly increased percentage changes relative to the OVA alone group in terms of airway hyperresponsiveness (AHR) and inflammatory cells, levels of IL-5 and thymus and activation regulated chemokine (TARC) in bronchoalveolar lavage (BAL) fluid than did Nrf2(+/+) mice. Lung tissues of Nrf2(-/-) mice after DEP exposure showed inflammatory cell infiltrates, and increased PAS staining-positive mucus cell hyperplasia. In contrast, the percentage changes relative to the OVA group in the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in whole blood was higher in Nrf2(+/+) mice than in Nrf2(-/-) mice. By using Nrf2(-/-) mice, it was shown for the first time that relatively low-dose DEP exposure induces oxidant stress, and that host anti-oxidant responses play a key role in the development of DEP-induced exacerbation of allergic airway inflammation.
authors.affiliation: Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan.
authors.forename: Ying Ji
authors.initials: YJ
authors.lastname: Li
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawada
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugawara
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D019803:Glutathione Disulfide / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D001335:Vehicle Emissions; D007073:Immunoglobulin E; D010047:Ovalbumin; D005978:Glutathione; D019803:Glutathione Disulfide