Tyrosine phosphatase SHP-1 in oxidative stress and development of allergic airway inflammation

Sook Cho You, Young Oh Sun, Zhou Zhu

Research output: Contribution to journalArticle

Abstract

Oxidative stress has been implicated in allergic responses. SHP-1 is a target of oxidants and has been reported as a negative regulator in a mouse model of asthma. We investigated the effect of oxidative stress on the development of allergic airway inflammation in heterozygous viable motheaten (mev/+) mice deficient of SHP-1. Wild-type (WT) and mev/+ mice were compared in this study. Human alveolar epithelial cells (A549) transfected with mutant SHP-1 gene were used to evaluate the role of SHP-1 in lung epithelial cells. Hydrogen peroxide (H2O2) and Paraquat were used in vitro and in vivo, respectively. We also investigated whether mev/+ mice can break immune tolerance when exposed to aeroallergen intranasally. Compared with WT mice, bronchoalveolar lavage (BAL) cells and splenocytes from mev/+ mice showed a different response to oxidant stress. This includes a significant enhancement of intracellular reactive oxygen species and STAT6 phosphorylation in vitro and increased CCL20, decreased IL-10, and increased number of dendritic cells in BAL fluid in vivo. Mutant SHP-1-transfected epithelial cells secreted higher levels of CCL20 and RANTES after exposure to oxidative stress. Furthermore, break of immune tolerance, as development of allergic airway inflammation, was observed in mev/+ mice after allergen exposure, which was suppressed by antioxidant N-acetylcystein. These data suggest that SHP-1 plays an important role in regulating oxidative stress. Thus, increased intracellular oxidative stress and lack of SHP-1 in the presence of T helper cell type 2-prone cellular activation may lead to the development of allergic airway inflammation.

Original languageEnglish (US)
Pages (from-to)412-419
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume39
Issue number4
DOIs
StatePublished - Oct 1 2008

Keywords

  • Allergen
  • Asthma
  • Immune tolerance
  • Oxidative stress
  • SHP-1

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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