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Gene expression of the GATA-3 transcription factor is increased in atopic asthma.

Authors: Nakamura, Y  Ghaffar, O  Olivenstein, R  Taha, RA  Soussi-Gounni, A  Zhang, DH  Ray, A  Hamid, Q 
Citation: Nakamura Y, etal., J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):215-22.
Pubmed: (View Article at PubMed) PMID:9949310

BACKGROUND: High expression of IL-5 by T cells in the airways of asthmatic individuals is believed to play a fundamental role in the eosinophilia associated with this disease. Recently, the transcription factor GATA-3 was shown to be critical for IL-5 gene expression in TH2 cells in vitro. OBJECTIVE: Our aim was to examine the expression of GATA-3 mRNA and its colocalization within the airways of asthmatic and nonasthmatic individuals. METHODS: We investigated the association between GATA-3 gene expression, airway inflammatory cells, and IL-5 gene expression in bronchoalveolar lavage fluid and bronchial biopsy specimens from atopic asthmatic subjects (n = 10) and normal control subjects (n = 10). RESULTS: We report that GATA-3 mRNA expression is significantly increased in the airways of asthmatic subjects compared with those of normal control subjects (P <.001). Numbers of cells expressing GATA-3 transcripts correlated significantly with reduced airway caliber (P <.05) and airways hyperresponsiveness (P <.05) in asthmatic subjects. Colocalization studies showed that the majority (approximately 60% to 90%) of GATA-3 mRNA+ cells in asthmatic airways were CD3(+) T cells, with smaller contributions from major basic protein+ eosinophils and tryptase+ mast cells. The density of GATA-3 mRNA+ cells correlated significantly with the numbers of cells expressing IL-5 mRNA (P <.001, r = 0.879 for bronchoalveolar lavage fluid; P <. 05, r = 0.721 for biopsy specimens). Furthermore, double in situ hybridization demonstrated that approximately 76% of GATA-3 mRNA+ cells coexpressed IL-5 mRNA and that 91% of IL-5 mRNA+ cells coexpressed GATA-3 mRNA. CONCLUSION: The results of this study provide the first evidence of increased GATA-3 gene expression in association with IL-5 mRNA+ cells in asthmatic airways. These findings support a causal association between augmented GATA-3 expression and dysregulated IL-5 expression in atopic asthma.

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CRRD Object Information
CRRD ID: 5128802
Created: 2011-03-17
Species: All species
Last Modified: 2011-03-17
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.