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

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-B 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.