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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Superoxide dismutase-overexpressing mice are resistant to ozone-induced tissue injury and increases in nitric oxide and tumor necrosis factor-alpha.

Authors: Fakhrzadeh, Ladan; Laskin, Jeffrey D; Gardner, Carol R; Laskin, Debra L

Published In Am J Respir Cell Mol Biol, (2004 Mar)

Abstract: Reactive oxygen intermediates have been implicated in lung injury induced by inhaled irritants. The present studies used mice overexpressing Cu/Zn-superoxide dismutase (SOD+/+) to analyze their role in ozone-induced lung inflammation and cytotoxicity. Treatment of wild-type mice with ozone (0.8 ppm, 3 h) resulted in increased bronchoalveolar lavage fluid protein, which was maximal after 24-48 h. Significant increases in lung macrophages and 4-hydroxyalkenals were also observed. In contrast, bronchoalveolar lavage fluid protein and macrophage content and 4-hydroxyalkenals were at control levels in ozone-treated SOD+/+ mice. There was also no evidence of peroxynitrite-mediated lung damage, demonstrating that SOD+/+ mice are resistant to ozone toxicity. Whereas alveolar macrophages from wild-type mice produced increased amounts of nitric oxide and expressed more inducible nitric oxide synthase, phospholipase A(2), and tumor necrosis factor-alpha after ozone inhalation, this was not evident in cells from SOD+/+ mice. Ozone-induced decreases in interleukin-10 were also not observed. In wild-type mice, ozone inhalation resulted in activation of nuclear factor-kappaB, which regulates proinflammatory gene activity. This response was significantly reduced in SOD+/+ mice. These data demonstrate that antioxidant enzymes play a critical role in ozone-induced tissue injury and in inflammatory mediator production.

PubMed ID: 12855403 Exiting the NIEHS site

MeSH Terms: Administration, Inhalation; Animals; Bronchoalveolar Lavage Fluid/chemistry; Cell Survival; Cyclooxygenase 1; Cyclooxygenase 2; Drug Resistance*; Electrophoretic Mobility Shift Assay; Female; Glutathione/metabolism; Interleukin-10/metabolism; Isoenzymes/metabolism; Lung Injury*; Lung/enzymology; Macrophages, Alveolar/metabolism; Macrophages, Alveolar/pathology; Malondialdehyde/metabolism; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; NF-kappa B/metabolism; Nitric Oxide Synthase Type II; Nitric Oxide Synthase/metabolism; Nitric Oxide/metabolism*; Ozone/administration & dosage; Ozone/toxicity*; Peroxynitrous Acid/metabolism; Phospholipases A/metabolism; Pneumonia/metabolism; Prostaglandin-Endoperoxide Synthases/metabolism; Reactive Oxygen Species; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism*; Tumor Necrosis Factor-alpha/metabolism*

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