T Helper Type 2 Cytokine Receptors and Associated Transcription Factors GATA-3, c-MAF, and Signal Transducer and Activator of Transcription Factor-6 in Induced Sputum of Atopic Asthmatic Patients

Abstract

It is well-known that the expression of T helper (Th) type 2 cytokines such as interleukin (IL)-4 and IL-5, and their receptors, is up-regulated within the airways of allergic asthmatic patients. Furthermore, higher numbers of cells producing GATA-3, c-MAF, and signal transducer and activator of transcription factor (STAT)-6, which are transcription factors (TFs) that are implicated in the regulation and signaling of the Th2 cytokines, have been observed in bronchial biopsy specimens from asthmatic patients but not in those of healthy control subjects. We examined whether these mediators also can be detected in induced sputum. Immunoreactivity for IL-4Ralpha, IL-5Ralpha, GATA-3, c-MAF, and STAT-6 was investigated in samples of induced sputum from asthmatic patients (n = 8) and healthy control subjects (n = 8). Our results showed that the numbers of cells expressing IL-4 receptor alpha (Ralpha) and IL-5Ralpha were higher in samples from asthmatic patients compared to those of control subjects (p < 0.01). More cells exhibiting GATA-3, c-MAF, and STAT-6 immunoreactivity also were found in asthmatic patients vs those in control subjects (p < 0.005). Furthermore, the expression of STAT-6 and IL-4Ralpha, GATA-3 and IL-5Ralpha, and c-MAF with both IL-4Ralpha and IL-5Ralpha was correlated (p < 0.05). This study demonstrated that induced sputum provides sufficient sensitivity for examining the pathways of cytokine signaling, cytokine receptor signaling, and intracellular signaling. Furthermore, these data show correlations between the expression of Th2 cytokine receptors and associated TFs in the human lung, which has not been documented previously.