title: Thioredoxin suppresses airway hyperresponsiveness and airway inflammation in asthma.
abstract: Thioredoxin (TRX) is a 12-kDa redox (reduction/oxidation)-active protein that has a highly conserved site (-Cys-Gly-Pro-Cys-) and scavenges reactive oxygen species. Here we examined whether exogenously administered TRX modulated airway hyperresponsiveness (AHR) and airway inflammation in a mouse asthma model. Increased AHR to inhaled acetylcholine and airway inflammation accompanied by eosinophilia were observed in OVA-sensitized mice. Administration of wild-type but not 32S/35S mutant TRX strongly suppressed AHR and airway inflammation, and upregulated expression of mRNA of several cytokines (e.g., IL-1alpha, IL-1beta, IL-1 receptor antagonist, and IL-18) in the lungs of OVA-sensitized mice. In contrast, TRX treatment at the time of OVA sensitization did not improve AHR or airway inflammation in OVA-sensitized mice. Thus, TRX inhibited the asthmatic response after sensitization, but did not prevent sensitization itself. TRX and redox-active protein may have clinical benefits in patients with asthma.
authors.affiliation: Department of Internal Medicine 1, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ichiki
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Haruki
authors.initials: H
authors.lastname: Imaoka
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013879:Thioredoxins / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D013879:Thioredoxins; D010047:Ovalbumin