期刊
EXPERIMENTAL AND MOLECULAR MEDICINE
卷 39, 期 6, 页码 756-768出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emm.2007.82
关键词
hypoxia-inducible factor-1; alpha subunit; lung inflammation; N-acetylcysteinamide; NF-kappa B; oxidative stress; respiratory hypersensitivity
Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AN on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AN in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AN decreased the increases of the NF-kappa B and hypoxia-inducible factor-la (HIF-1 alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappa B and HIF-1 alpha as well as reducing ROS generation in allergic airway disease.
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