title: Airway inflammatory responses to oxidative stress induced by low-dose diesel exhaust particle exposure differ between mouse strains.
abstract: Low-dose diesel exhaust particle (DEP) exposure induces airway inflammation and exaggerates asthmatic responses in mice, but it is unclear whether strains differ in their susceptibility to adverse effects from low-dose DEP exposure. The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to low-dose DEP (100 microg/m(3)) exposure in terms of airway inflammatory response. The macrophage count in bronchoalveolar lavage (BAL) fluid soon after DE exposure began was significantly greater in C57BL/6 mice (P < .05) than that in BALB/c mice. The count did not increase significantly in BALB/c mice until later. Heme oxygenase-1 (HO-1) mRNA expression and protein production in lung tissues soon after exposure began were more marked in BALB/c mice than in C57BL/6 mice, but the reverse was true later on. The increases in interleukin (IL)-1beta and interferon (IFN)-gamma levels in BAL fluid after DE exposure were significant only in BALB/c mice; there were significantly increases in monocyte chemoattractant protein (MCP)-1, IL-12, IL-10, IL-4, and IL-13 in both strains, but these were more marked in C57BL/6 mice. These interstrain differences in airway inflammatory response after DE exposure were significantly attenuated by antioxidant N-acetylcysteine (NAC) treatment. Changes in airway hyperresponsiveness were independent of the airway inflammation induced by low-dose DEP. Thus, in BALB/c mice, innate immunity may play a central role in DE exposure response, whereas in C57BL/6 mice Th2-dominant responses play a central role. Low-dose DEP exposure induces airway inflammatory responses that differ among strains, and these differences may be caused by differences in sensitivity to oxidative stress.
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: Tomoyuki
authors.initials: T
authors.lastname: Kawada
authors.forename: Aki
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugawara
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013045:Species Specificity; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D012333:RNA, Messenger; D001335:Vehicle Emissions; D051547:Heme Oxygenase-1; D000111:Acetylcysteine