Document Detail


Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation.
MedLine Citation:
PMID:  20017193     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress plays an important role in the pathogenesis of asthma via the upregulation of local inflammatory mediators and/or promoting Th2-skewing during Ag sensitization. Thioredoxin (TRX), a 12 kDa redox-active protein with antioxidative property, has been recently shown to play a protective role in various inflammatory diseases. Using a mouse model of asthma, we show here that IL-13 and eotaxin production are decreased in TRX-Tg mice leading to reduced eosinophils recruitment and mucus metaplasia. The reduction in airway inflammation occurs without the attenuation of systemic Th2 immunity in that comparable levels of Th2-type cytokines and Ig were detected in LN and serum, respectively, from TRX-Tg and WT mice. Likewise, CD4(+) T cells from both strains of mice developed similar Th1 and Th2 responses in vitro. Asthmatic lungs of TRX-Tg and WT mice contained similar amounts of GATA-3(+) and Foxp3(+) T cells. Finally, production of MIF, an upstream modulator of airway inflammation, was significantly reduced in the lungs of TRX-Tg mice. Our data suggest that TRX suppresses airway inflammation by inhibiting MIF production thereby limiting the downstream recruitment of eosinophils to the lung independently of modulating systemic Th1/Th2 immunity.
Authors:
Mie Torii; Linan Wang; Ning Ma; Kanako Saito; Tomohide Hori; Maremi Sato-Ueshima; Yoshikazu Koyama; Hiroyoshi Nishikawa; Naoyuki Katayama; Akira Mizoguchi; Hiroshi Shiku; Junji Yodoi; Kagemasa Kuribayashi; Takuma Kato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  40     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-11     Completed Date:  2010-04-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  787-96     Citation Subset:  IM    
Affiliation:
Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine, Tsu, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Asthma / immunology*,  metabolism
Cell Differentiation / immunology
Chemotaxis, Leukocyte / immunology
Enzyme-Linked Immunosorbent Assay
Eosinophils / immunology
Humans
Interleukin-13 / biosynthesis,  metabolism
Intramolecular Oxidoreductases / immunology
Macrophage Migration-Inhibitory Factors / immunology
Mice
Mice, Transgenic
Pneumonia / immunology*,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Th1 Cells / cytology,  immunology*
Th2 Cells / cytology,  immunology*
Thioredoxins / immunology*
Chemical
Reg. No./Substance:
0/Interleukin-13; 0/Macrophage Migration-Inhibitory Factors; 52500-60-4/Thioredoxins; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.2.1/Mif protein, mouse

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