An antioxidant modulates expression of receptor activator of NF-kappaB
in asthma.
Lee KS, Park HS, Park SJ, Kim SR, Min KH, Jin SM, Li1 L, Lee YC
Exp Mol Med. 2006 Jun 30; 38(3): 217-229

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.

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