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

• Published in: Journal of allergy and clinical immunology Vol. 103; no. 2; pp. 215 - 222
• Main Authors: Nakamura, Yutaka, Ghaffar, Omar, Olivenstein, Ronald, Taha, Rame A., Soussi-Gounni, Abdelilah, Zhang, Dong-Hong, Ray, Anuradha, Hamid, Qutayba
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-02-1999; Elsevier
• Subjects: Adult; Allergic diseases; Asthma; Asthma - metabolism; Biological and medical sciences; Bronchi - metabolism; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; eosinophils; Female; GATA-3; GATA3 Transcription Factor; Gene Expression Regulation - immunology; Humans; Hypersensitivity, Immediate - metabolism; IL-5; Immunochemistry; Immunopathology; In Situ Hybridization; Interleukin-5 - biosynthesis; Male; Medical sciences; Middle Aged; Phenotype; Respiratory and ent allergic diseases; RNA, Messenger - metabolism; T lymphocytes; Trachea - metabolism; Trans-Activators - biosynthesis; Trans-Activators - genetics; Transcription Factors - biosynthesis; Transcription Factors - genetics; T lymphocytes; NF-κB; SSC; IL-5; eosinophils; MBP; BAL; GATA-3; Asthma; Human; Immunopathology; Allergy; Pathophysiology; Respiratory disease; Cytokine; Granulocyte; Regulator gene; Gene expression; Eosinophil; Promoter; Interleukin 5; T-Lymphocyte; Genetics; Obstructive pulmonary disease; Transcription factor
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(99)70493-8

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 T
H2 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. (J Allergy Clin Immunol 1999;103:215-22.)