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

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

Research output: Contribution to journalArticle

20 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
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor
Asthma
Antioxidants
Capillary Permeability
Carboxylic Acids
Messenger RNA
Inflammation
Plasmas
Lung
Oxidative stress
Endothelial cells
Ovalbumin
Prodrugs
Inbred C57BL Mouse
Allergens
Inhalation
Cysteine
Oxidative Stress
Up-Regulation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

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

An antioxidant modulates expression of receptor activator of NF-κB in asthma. / Kyung, Sun Lee; Hee, Sun Park; Seoung, Ju Park; So, Ri Kim; Min, Kyung-Hoon; Sun, Mi Jin; Li, Liangchang; Yong, Chul Lee.

In: Experimental and Molecular Medicine, Vol. 38, No. 3, 30.06.2006, p. 217-229.

Research output: Contribution to journalArticle

Kyung, SL, Hee, SP, Seoung, JP, So, RK, Min, K-H, Sun, MJ, Li, L & Yong, CL 2006, 'An antioxidant modulates expression of receptor activator of NF-κB in asthma', Experimental and Molecular Medicine, vol. 38, no. 3, pp. 217-229.
Kyung, Sun Lee ; Hee, Sun Park ; Seoung, Ju Park ; So, Ri Kim ; Min, Kyung-Hoon ; Sun, Mi Jin ; Li, Liangchang ; Yong, Chul Lee. / An antioxidant modulates expression of receptor activator of NF-κB in asthma. In: Experimental and Molecular Medicine. 2006 ; Vol. 38, No. 3. pp. 217-229.
@article{a682536d349a446a8de8eb2b683e9e1e,
title = "An antioxidant modulates expression of receptor activator of NF-κB in asthma",
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.",
keywords = "Capillary permeability, Eosinophilia, Oxidative stress, Signal transduction, Vascular endothelial growth factor",
author = "Kyung, {Sun Lee} and Hee, {Sun Park} and Seoung, {Ju Park} and So, {Ri Kim} and Kyung-Hoon Min and Sun, {Mi Jin} and Liangchang Li and Yong, {Chul Lee}",
year = "2006",
month = "6",
day = "30",
language = "English",
volume = "38",
pages = "217--229",
journal = "Experimental and Molecular Medicine",
issn = "1226-3613",
publisher = "Korean Society of Med. Biochemistry and Mol. Biology",
number = "3",

}

TY - JOUR

T1 - An antioxidant modulates expression of receptor activator of NF-κB in asthma

AU - Kyung, Sun Lee

AU - Hee, Sun Park

AU - Seoung, Ju Park

AU - So, Ri Kim

AU - Min, Kyung-Hoon

AU - Sun, Mi Jin

AU - Li, Liangchang

AU - Yong, Chul Lee

PY - 2006/6/30

Y1 - 2006/6/30

N2 - 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.

AB - 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.

KW - Capillary permeability

KW - Eosinophilia

KW - Oxidative stress

KW - Signal transduction

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=33745863849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745863849&partnerID=8YFLogxK

M3 - Article

VL - 38

SP - 217

EP - 229

JO - Experimental and Molecular Medicine

JF - Experimental and Molecular Medicine

SN - 1226-3613

IS - 3

ER -