A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-êB and hypoxia-inducible factor-1α

Sun Lee Kyung, Ri Kim So, Sun Park Hee, Ju Park Seoung, Hoon Min Kyung, Young Lee Ka, Hun Choe Yeong, Hyun Hong Sang, Jin Han Hyo, Rae Lee Young, Suk Kim Jong, Daphne Atlas, Chul Lee Yong

Research output: Contribution to journalArticle

61 Citations (Scopus)

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-κB and hypoxia-inducible factor-1α (HIF-1α) 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-κB and HIF-1α as well as reducing ROS generation in allergic airway disease.

Original languageEnglish
Pages (from-to)756-768
Number of pages13
JournalExperimental and Molecular Medicine
Volume39
Issue number6
DOIs
Publication statusPublished - 2007 Dec 31
Externally publishedYes

Keywords

  • Hypoxia-inducible factor-1, α subunit
  • Lung inflammation
  • N-acetylcysteinamide
  • NF-κB
  • Oxidative stress
  • Respiratory hypersensitivity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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  • Cite this

    Kyung, S. L., So, R. K., Hee, S. P., Seoung, J. P., Kyung, H. M., Ka, Y. L., Yeong, H. C., Sang, H. H., Hyo, J. H., Young, R. L., Jong, S. K., Atlas, D., & Yong, C. L. (2007). A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-êB and hypoxia-inducible factor-1α. Experimental and Molecular Medicine, 39(6), 756-768. https://doi.org/10.1038/emm.2007.82