Involvement of GATA-3-dependent Th2 lymphocyte activation in airway hyperresponsiveness

Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1045-51. doi: 10.1152/ajplung.00195.2005. Epub 2006 Feb 17.

Abstract

The pathophysiological characteristics of bronchial asthma consist of chronic inflammation of airways, airway hyperresponsiveness, and bronchoconstriction. Studies have shown that T helper type 2 (Th2) cytokines produced by both T cells and mast cells in the airway contribute substantially to the initiation of inflammation in both experimental and human bronchial asthma. GATA-3 is a transcription factor essential to the production of Th2 cytokines by T lymphocytes. To clarify the role of GATA-3-expressing T cells in the pathophysiology of bronchial asthma, we utilized transgenic (Tg) mice carrying the GATA-3 gene and the ovalbumin (OVA)-specific T cell receptor gene (GATA-3-Tg/OVA-Tg). Mice were intranasally administrated OVA without systemic immunization. Airway responses were analyzed with noninvasive and invasive whole body plethysmographs. GATA-3-Tg/OVA-Tg mice exhibited significantly higher IL-13 and IL-4 protein expression in the airway. Although there were no differences in the types of infiltrating cells between GATA-3-Tg/OVA-Tg and GATA-3-non-Tg/OVA-Tg mice and no significant increase in IgE level in either group compared with nontreated mice, the response after ACh inhalation was significantly elevated in GATA-3-Tg/OVA-Tg on the seventh day of intranasal treatment with OVA. This hyperresponsiveness was inhibited by 5-lipoxygenase inhibitor and IL-13 neutralization, suggesting that airway responses were induced through IL-13 and leukotriene pathway. In conclusion, airway hyperresponsiveness, a characteristic of bronchial asthma, is regulated at the level of GATA-3 transcription by T lymphocytes in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Obstruction / physiopathology*
  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism
  • Bronchoalveolar Lavage Fluid
  • DNA Primers
  • Disease Models, Animal
  • GATA3 Transcription Factor / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Ovalbumin / genetics
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th2 Cells / immunology*

Substances

  • DNA Primers
  • GATA3 Transcription Factor
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Ovalbumin
  • Arachidonate 5-Lipoxygenase