title: An antioxidant modulates expression of receptor activator of NF-kappaB 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-kappaB (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 pathophysiological 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.
authors.affiliation: Department of Internal Medicine, Airway Remodeling Laboratory, Research Center for Allergic Immune Diseases Chonbuk National University Medical School, Jeonju 561-712, Korea.
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Lee
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Seoung Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: So Ri
authors.initials: SR
authors.lastname: Kim
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Jin
authors.forename: Liangchang
authors.initials: L
authors.lastname: Li
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002199:Capillary Permeability / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053244:Osteoprotegerin; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D011355:Prodrugs / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006023:Glycoproteins; D053244:Osteoprotegerin; D011355:Prodrugs; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D013844:Thiazoles; D053778:Thiazolidines; C506031:Tnfrsf11b protein, mouse; D042461:Vascular Endothelial Growth Factor A; D010047:Ovalbumin; D040262:Receptors, Vascular Endothelial Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid