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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/L1045    most recent 00195.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Yamashita, N. Articles by Ohta, K. Search for Related Content PubMed PubMed Citation Articles by Yamashita, N. Articles by Ohta, K.

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

¹Department of Medicine, Teikyo University School of Medicine, Tokyo; ²Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo; ³Department of Microbiology, Kitazato University School of Medicine, Kanagawa; ⁴Pharmacology Research Laboratories, Dainippon Sumitomo Pharmaceutical Corporation, Osaka; and ⁵Division of Host Defense Mechanism, Department of Immunology, Tokai University School of Medicine, Kanagawa, Japan

Submitted 28 April 2005 ; accepted in final form 19 December 2005

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.

T helper type 2 cytokines; transgenic mice; allergic inflammation