title: Effects of thioredoxin on established airway remodeling in a chronic antigen exposure asthma model.
abstract: 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-1alpha 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.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Imaoka
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Satoko
authors.initials: S
authors.lastname: Takei
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sakazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Masaki
authors.initials: M
authors.lastname: Okamoto
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Kawayama
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D010047:Ovalbumin; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D013879:Thioredoxins / Q000494:pharmacology*; D013995:Time
chemical_list: C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D019742:Chemokines, CC; D018793:Interleukin-13; D019402:Macrophage Inflammatory Proteins; D013879:Thioredoxins; D010047:Ovalbumin