PT  - JOURNAL ARTICLE
AU  - Lee, Kyung Sun
AU  - Park, Hee Sun
AU  - Park, Seoung Ju
AU  - Kim, So Ri
AU  - Min, Kyung Hoon
AU  - Jin, Sun Mi
AU  - Park, Kwang-Hyun
AU  - Kim, Uh-Hyun
AU  - Kim, Chan Young
AU  - Lee, Yong Chul
TI  - A Prodrug of Cysteine, <span class="sc">l</span>-2-Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing Vascular Endothelial Growth Factor Expression in Asthma
AID  - 10.1124/mol.105.016055
DP  - 2005 Nov 01
TA  - Molecular Pharmacology
PG  - 1281--1290
VI  - 68
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/68/5/1281.short
4100  - http://molpharm.aspetjournals.org/content/68/5/1281.full
SO  - Mol Pharmacol2005 Nov 01; 68
AB  - Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Oxidative stress plays critical roles in airway inflammation. Although reactive oxygen species (ROS) are shown to cause vascular leakage, the mechanisms by which ROS induce increased vascular permeability are not clearly understood. We have used a murine model of asthma to evaluate the effect of l-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine that acts as an antioxidant, more specifically in the increase of vascular permeability. These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased vascular permeability, and increased levels of vascular endothelial growth factor (VEGF). Administration of OTC markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. We also showed that at 72 h after ovalbumin inhalation, increased levels of hypoxia-inducible factor-1α (a transcriptional activator of VEGF) in nuclear protein extracts of lung tissues were decreased by the administration of OTC. These results indicate that OTC modulates vascular permeability by lowering VEGF expression.