An antioxidant modulates expression of receptor activator of NF-κB in asthma

Sun Lee Kyung, Sun Park Hee, Ju Park Seoung, Ri Kim So, Hoon Min Kyung, Mi Jin Sun, Liangchang Li, Chul Lee Yong

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Oxidative stress plays critical roles in airway inflammation that is usually accompanied by increased vascular permeability and plasma exudation. VEGF increases vascular permeability and leads to airway inflammation. In addition, VEGF has been shown to enhance receptor activator of NF-κB (RANK) expression in endothelial cells. An aim of the study was to determine the potential role of antioxidant in the regulation of RANK expression in murine model of asthma. We have used a C57BL/6 mouse model of allergic asthma to evaluate the effect of L-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, which acts as an antioxidant, and VEGF receptor inhibitor on RANK mRNA expression. The mice develop the following patho-physiological features of asthma in the lungs: increased expression of RANK mRNA, increased number of inflammatory cells of the airways, increased vascular permeability, and increased levels of VEGF. Administration of OTC and VEGF receptor inhibitor markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. We also showed that the increased RANK mRNA expression at 72 h after ovalbumin inhalation were reduced by the administration of OTC or VEGF receptor inhibitor. The results indicate that OTC and VEGF receptor inhibitor which inhibit up-regulation of VEGF expression modulate RANK expression that may be in association with the regulation of vascular permeability, and suggest that VEGF may regulate the RANK expression. These findings provide a crucial molecular mechanism for the potential use of antioxidants to prevent and/or treat asthma and other airway inflammatory disorders.

Original languageEnglish
Pages (from-to)217-229
Number of pages13
JournalExperimental and Molecular Medicine
Volume38
Issue number3
Publication statusPublished - 2006 Jun 30

Keywords

  • Capillary permeability
  • Eosinophilia
  • Oxidative stress
  • Signal transduction
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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  • Cite this

    Kyung, S. L., Hee, S. P., Seoung, J. P., So, R. K., Kyung, H. M., Sun, M. J., Li, L., & Yong, C. L. (2006). An antioxidant modulates expression of receptor activator of NF-κB in asthma. Experimental and Molecular Medicine, 38(3), 217-229.