A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha.
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.
Lee
Kyung Sun
KS
Department of Internal Medicine and Airway Remodeling Laboratory, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Kim
So Ri
SR
Park
Hee Sun
HS
Park
Seoung Ju
SJ
Min
Kyung Hoon
KH
Lee
Ka Young
KY
Choe
Yeong Hun
YH
Hong
Sang Hyun
SH
Han
Hyo Jin
HJ
Lee
Young Rae
YR
Kim
Jong Suk
JS
Atlas
Daphne
D
Lee
Yong Chul
YC
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
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