Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice.
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.
Li
Ying Ji
YJ
Department of Hygiene and Public Health, Nippon Medical School, Tokyo, Japan.
Takizawa
Hajime
H
Azuma
Arata
A
Kohyama
Tadashi
T
Yamauchi
Yasuhiro
Y
Takahashi
Satoru
S
Yamamoto
Masayuki
M
Kawada
Tomoyuki
T
Kudoh
Shoji
S
Sugawara
Isamu
I
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*
D000975:Antioxidants; D016207:Cytokines; D007074:Immunoglobulin G; D051267:NF-E2-Related Factor 2; D001335:Vehicle Emissions; D007073:Immunoglobulin E