Premium
Blockade of airway hyperresponsiveness and inflammation in a murine model of asthma by a prodrug of cysteine, L‐2‐ oxothiazolidine‐4‐carboxylic acid
Author(s) -
Lee Yong Chul,
Lee Kyung Sun,
Park Seoung Ju,
Park Hee Sun,
Lim Jae Sung,
Park KwangHyun,
Im MieJae,
Choi IlWhan,
Lee HernKu,
Kim UhHyun
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2212fje
Subject(s) - bronchoalveolar lavage , ovalbumin , inhalation , pharmacology , inflammation , eosinophil , medicine , oxidative stress , immunology , glutathione , reactive oxygen species , allergic inflammation , bronchial hyperresponsiveness , chemistry , asthma , lung , biochemistry , respiratory disease , anesthesia , immune system , enzyme
Oxidative stress plays an important role in the pathogenesis of bronchial asthma. An excess production of reactive oxygen species (ROS) and defective endogenous antioxidant defense mechanisms may be present in asthma. Reduced glutathione (GSH) is one of the most important reducing agents against oxidant free radicals. A reducing agent, L‐2‐oxothiazolidine‐4‐ carboxylic acid (OTC), a prodrug of cysteine, increases intracellular GSH. We have used a mouse model for asthma to determine effects of OTC on allergen‐induced bronchial inflammation and airway hyper‐responsiveness. The administration of OTC reduced bronchial inflammation and airway hyper‐responsiveness. ROS generation in bronchoalveolar lavage fluids was increased by ovalbumin (OVA) inhalation, but this increase was diminished by administration of OTC. The increased IL‐4, IL‐5, IL‐13, and eosinophil cationic protein levels in lungs after OVA inhalation were significantly reduced by the administration of OTC. In addition, the increased expression of ICAM‐1, VCAM‐1, RANTES, and eotaxin in lungs after OVA inhalation was significantly reduced by the administration of OTC. We also showed that the increased NF‐κB levels in nuclear protein extracts of lung tissues at 72 h after OVA inhalation were decreased by the administration of OTC. These findings suggest that OTC may reduce airway inflammation and hyper‐responsiveness through regulation of NF‐κB activity.