Effects of thioredoxin on established airway remodeling in a chronic antigen exposure asthma model

• Published in: Biochemical and biophysical research communications Vol. 360; no. 3; pp. 525 - 530
• Main Authors: Imaoka, Haruki, Hoshino, Tomoaki, Takei, Satoko, Sakazaki, Yuki, Kinoshita, Takashi, Okamoto, Masaki, Kawayama, Tomotaka, Yodoi, Junji, Kato, Seiya, Iwanaga, Tomoaki, Aizawa, Hisamichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.08.2007
• Subjects: Animals; Asthma; Asthma - chemically induced; Asthma - drug therapy; Asthma - pathology; Bronchi - drug effects; Bronchi - pathology; Chemokine CCL11; Chemokine CCL4; Chemokines; Chemokines, CC - metabolism; Disease Models, Animal; Disease Progression; Female; Humans; Interleukin-13 - metabolism; Lung - drug effects; Lung - pathology; Macrophage Inflammatory Proteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Transgenic; Muscle, Smooth - drug effects; Muscle, Smooth - pathology; Ovalbumin; Pneumonia - chemically induced; Pneumonia - pathology; Pneumonia - prevention & control; Remodeling; Th2 cytokines; Thioredoxins - pharmacology; Time; Transgenic mouse; Transgenic mouse; Th2 cytokines; Remodeling; Chemokines; Asthma
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.06.019

The development and treatment of asthma remains a subject of considerable interest in the medical community. Previous studies implicate an important role of cytokines in the pathology of asthma. In this current study, we examined whether redox-active protein thioredoxin 1 (TRX1) could prevent airway remodeling in an ovalbumin (OVA)-driven mouse chronic antigen exposure asthma model. Balb/c mice were sensitized and then challenged nine times with OVA (days 19–45). In this protocol, airway remodeling was established by day 34. Administration of recombinant human TRX1 during antigen challenge (days 18–32) significantly inhibited airway remodeling, eosinophilic pulmonary inflammation, airway hyperresponsiveness and resulted in decreased lung expression of eotaxin, macrophage inflammatory protein-1α and IL-13. Airway remodeling and eosinophilic pulmonary inflammation was also prevented in chronic OVA-exposed Balb/c human TRX1 transgenic mice. Importantly, TRX1-administration, after the establishment of airway remodeling (days 35–45), resulted in improved airway pathology. Our results suggest TRX1 prevents the development of airway remodeling, and also improves established airway remodeling by inhibiting production of chemokines and Th2 cytokines in the lungs.