Recent studies have provided evidence for increased IL-4 expression in the airways of atopic and nonatopic asthmatic subjects. IL-4 is believed to perform important regulatory roles in asthma; however, the expression of the IL-4 receptor has not been investigated. In this study we examined the mRNA and protein expression of the specific α-subunit of the IL-4 receptor (αIL-4R) in bronchial biopsy specimens obtained from atopic and nonatopic asthmatic subjects.Methods:
Asthmatic subjects and nonasthmatic control subjects were recruited, and lung function measurements were performed before bronchoscopy. Endobronchial biopsy specimens were examined for the presence of αIL-4R mRNA and immunoreactivity by using in situ hybridization and immunocytochemistry, respectively.Results:
αIL-4R mRNA-positive and immunoreactive cells were detected in the epithelium and subepithelium in biopsy specimens from all subjects. Expression of αIL-4R mRNA and protein was significantly increased in the epithelium and subepithelium of biopsy specimens from atopic asthmatic subjects compared with atopic control subjects (P < .05 and P < .001, respectively). Epithelial αIL-4R mRNA expression and immunoreactivity did not differ significantly between nonatopic asthmatic subjects and nonatopic control subjects. Although the numbers of αIL-4R mRNA-positive cells were augmented in the submucosa of intrinsic asthmatic subjects compared with nonatopic control subjects (P < .05), αIL-4R immunoreactivity did not differ significantly between these groups. Increased αIL-4R immunoreactive signals were also detected in the endothelial cell layer in both atopic and intrinsic asthmatic subjects compared with atopic and nonatopic control subjects, respectively (P < .05). Combined in situ hybridization immunocytochemistry performed on biopsy sections from asthmatic and control subjects demonstrated αIL-4R mRNA expression in CD3-positive T cells and tryptase-positive mast cells, with T cells comprising the larger proportion of αIL-4R mRNA-positive cells. Numbers of αIL-4R mRNA-positive or immunoreactive cells did not correlate with CD3-positive cell numbers, numbers of IL-4 mRNA-positive cells, or indices of pulmonary function.Conclusion:
These results demonstrate constitutive αIL-4R expression in normal airways and enhanced expression in airway tissue from asthmatic individuals.