Thioredoxin suppresses airway inflammation independently of systemic Th1/Th2 immune modulation

Eur J Immunol. 2010 Mar;40(3):787-96. doi: 10.1002/eji.200939724.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology*
  • Asthma / metabolism
  • Cell Differentiation / immunology
  • Chemotaxis, Leukocyte / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Eosinophils / immunology
  • Humans
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / metabolism
  • Intramolecular Oxidoreductases / immunology
  • Macrophage Migration-Inhibitory Factors / immunology
  • Mice
  • Mice, Transgenic
  • Pneumonia / immunology*
  • Pneumonia / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Thioredoxins / immunology*

Substances

  • Interleukin-13
  • Macrophage Migration-Inhibitory Factors
  • Thioredoxins
  • Intramolecular Oxidoreductases
  • Mif protein, mouse