TH2 cytokine–associated transcription factors in atopic and nonatopic asthma: Evidence for differential signal transducer and activator of transcription 6 expression

• Published in: Journal of allergy and clinical immunology Vol. 107; no. 4; pp. 586 - 591
• Main Authors: Christodoulopoulos, Pota, Cameron, Lisa, Nakamura, Yutaka, Lemière, Catherine, Muro, Shigeo, Dugas, Mario, Boulet, Louis-Philippe, Laviolette, Michel, Olivenstein, Ron, Hamid, Qutayba
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.04.2001; Elsevier
• Subjects: Adult; Aged; Allergic diseases; Asthma - metabolism; Atopic asthma; Biological and medical sciences; cMAF; DNA-Binding Proteins - analysis; Female; GATA-3; GATA3 Transcription Factor; Humans; Hypersensitivity - metabolism; IL-4; Immunohistochemistry; Immunopathology; Interleukin-4 - pharmacology; Male; Medical sciences; Middle Aged; nonatopic asthma; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins c-maf; Receptors, Interleukin-4 - physiology; Respiratory and ent allergic diseases; STAT-6; STAT6 Transcription Factor; Th2 Cells - physiology; Trans-Activators - analysis; transcription factors; Atopic asthma; cMAF; PC20; nonatopic asthma; transcription factors; IL-4; STAT-6; GATA-3; IL-4R; Human; Immunohistochemistry; Immunopathology; Allergy; Respiratory disease; Cytokine; Differential diagnostic; Asthma; Atopy; Transcription factor GATA3; Pathology; Interleukin 4; Transcription factor STAT6; Obstructive pulmonary disease; Diagnosis; Transcription factor
• ISSN: 0091-6749
• DOI: 10.1067/mai.2001.114883

Background: The expression of IL-4 and IL-5 is increased in patients with atopic asthma compared with control subjects and correlates with indices of pulmonary function. In nonatopic asthma the expression of IL-4, unlike IL-5, fails to correlate with pulmonary function, and compared with their atopic counterparts, these patients have fewer cells expressing IL-4 receptor (IL-4R). As such, a deficiency in the IL-4 signaling pathway may be implicated in nonatopic asthma. The transcription factors GATA-3 and cMAF mediate IL-4 and IL-5 synthesis, whereas signal transducer and activator of transcription 6 (STAT-6) is critical for IL-4R signaling. Objective: This study examines the expression profile of these transcription factors in asthma, according to atopic status. Methods: With immunocytochemistry, the expression of GATA-3, cMAF, and STAT-6 protein was determined in sections of bronchial biopsy specimens from patients with atopic asthma (n = 7), patients with nonatopic asthma (n = 8), and control subjects (n = 8). Results: Higher numbers of cells expressing GATA-3 and cMAF were observed in patients with atopic and those with nonatopic asthma than in control subjects and patients with tuberculosis (P < .001). There were also more STAT-6–immunoreactive cells in patients with atopic and those with nonatopic asthma than in control subjects (P < .0001, P < .05). Notably, however, fewer cells expressing STAT-6 protein were observed in nonatopic versus atopic asthma (P < .0001). Conclusions: These results demonstrate the upregulation of GATA-3 and cMAF in both variants of asthma and indicate that reduced IL-4R signaling, because of lower STAT-6 expression, may be a feature of nonatopic asthma. (J Allergy Clin Immunol 2001;107:586-91.)