Redox-regulated mechanisms in asthma.
Homeostasis of the reduction-oxidation (redox) state is critical to protection from oxidative stress in the lungs. Therefore, the lungs have high levels of antioxidants, including glutathione, heme oxygenase, and superoxide dismutase. The numbers of inflammatory cells -- particularly eosinophils -- are increased in the airways of asthma patients, and these pulmonary inflammatory cells release large amounts of harmful reactive oxygen species and reactive nitrogen species. Human thioredoxin 1 (TRX1) is a redox-active protein of approximately 12 kDa that contains a (32)Cys-Gly-Pro-(35)Cys sequence necessary for its activity. The strong reducing activity of the sequence results from the cysteine residues acting as proton donors and cleaving disulfide (S-S) bonds in the target protein. Endogenous or exogenous TRX1 or both protect the lungs against ischemia-reperfusion injury, influenza infection, bleomycin-induced injury, or lethal pulmonary inflammation caused by interleukin-2 and interleukin-18. We showed that exogenous TRX1 inhibits airway hyperresponsiveness and pulmonary inflammation accompanied by eosinophilia in mouse models of asthma. Recently, we reported that exogenous TRX1 improves established airway remodeling in a prolonged antigen-exposure mouse asthma model. Exogenous and endogenous TRX1 also prevents the development of airway remodeling. Here, we discuss the role and clinical benefits of TRX1 in asthma.
Hoshino
Tomoaki
T
Divisions of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan. hoshino@med.kurume-u.ac.jp
Okamoto
Masaki
M
Takei
Satoko
S
Sakazaki
Yuki
Y
Iwanaga
Tomoaki
T
Aizawa
Hisamichi
H
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001249:Asthma / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D013879:Thioredoxins / Q000097:blood / Q000378:metabolism*
D000975:Antioxidants; D013879:Thioredoxins; D013482:Superoxide Dismutase; D005978:Glutathione