title: Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice.
abstract: To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative stress and host antioxidant responses play a key role in the development of DEP-induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose DEP for 7 h/day, 5 days/week, for 8 weeks. Nrf2(-/-) mice exposed to low-dose DEP showed significantly increased airway hyperresponsiveness and counts of lymphocytes and eosinophils, together with increased concentrations of IL-12 and IL-13, and thymus and activation-regulated chemokine (TARC), in BAL fluid than wild-type mice. In contrast, expression of antioxidant enzyme genes was significantly higher in wild-type mice than in Nrf2(-/-) mice. We have first demonstrated that disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by inhalation of low-dose DEP in mice. These results strongly suggest that DEP-induced oxidative stress and host antioxidant responses play some role in the development of DEP-induced 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; D000975:Antioxidants / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004198:Disease Susceptibility; D004790:Enzyme Induction; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D019570:Inhalation Exposure; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D007074:Immunoglobulin G; D051267:NF-E2-Related Factor 2; D001335:Vehicle Emissions; D007073:Immunoglobulin E