Upregulation of the transcription factor GATA-3 in upper airway mucosa after in vivo and in vitro allergen challenge

Abstract

Background: Allergic rhinitis is a complex upper airways disorder characterized by the infiltration of eosinophils and TH2-type T lymphocytes. GATA-3 is a novel transcription factor recently shown to regulate IL-5 and, possibly, IL-4 gene expression. We previously reported that GATA-3 is increased within the bronchial mucosa of allergic asthmatic subjects compared with control subjects. Objective: In the present study we set out to determine whether there is also an increased number of cells expressing GATA-3 messenger (m)RNA within the nasal mucosa of patients with allergic rhinitis. Methods: Inferior turbinate biopsy specimens were obtained from patients with allergic rhinitis and nonatopic control subjects before and after local allergen provocation in vivo. To assess the contribution of resident cells expressing GATA-3 mRNA, we also performed isolated explant studies in which nasal mucosal tissue from subjects with allergic rhinitis and nonatopic control subjects was cultured in allergen-treated medium. The presence of mRNA coding for GATA-3, IL-5, IL-4, IL-13, and GM-CSF was assessed by using in situ hybridization. Results: The number of GATA-3 mRNA+ cells was increased after local allergen provocation in vivo (increase in GATA-3 mRNA+ cells [mean ± SEM]: subjects with allergic rhinitis, 11.3 ± 8.7; control subjects, 1.2 ± 4.1; P < .05) and in explanted nasal mucosa in vitro (subjects with allergic rhinitis, 10.2 ± 3.8; control subjects, 2.7 ± 4.4; P < .05). The gene expression of GATA-3 was significantly correlated to the numbers of IL-5 (r = 0.87) and GM-CSF (r = 0.79) mRNA+ cells but not with IL-4 or IL-13 mRNA+ cells. Conclusion: In summary, the expression of the transcription factor GATA-3 was increased after allergen challenge, and this was evident in the absence of de novo inflammatory cell recruitment. GATA-3 may be a potential target in the treat-ment of allergic diseases, such as rhinitis. Copyright ©2000 by Mosby, Inc.