title: A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.
abstract: 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 AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 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 AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) 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-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.
authors.affiliation: Department of Internal Medicine and Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju 561-180, Korea.
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Lee
authors.forename: So Ri
authors.initials: SR
authors.lastname: Kim
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Seoung Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Ka Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Yeong Hun
authors.initials: YH
authors.lastname: Choe
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Hong
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Han
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Daphne
authors.initials: D
authors.lastname: Atlas
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C487056:N-Acetylcysteinamide; D010047:Ovalbumin; D000111:Acetylcysteine