In vivo expression of signal transducer and activator of transcription factor 6 (STAT6) in nasal mucosa from atopic allergic rhinitis: effect of topical corticosteroids

Background The allergen-induced late nasal response is associated with a hi gh local expression of interleukin (IL) -4, a TH2-type cytokine implicated in immunoglobulin (Ig) E production, tissue eosinophilia and other events c onsidered to be relevant to allergic inflammation. Interaction of IL-4 with its receptor activates at least two distinct signalling pathways that culm inate in the transcription of specific target genes. One pathway involves t he activation of a transcription factor termed signal transducer and activa tor of transcription factor 6 (STAT6). Objective To investigate the expression of STATE in the allergen-induced la te nasal response and to examine the effect of local steroid treatment on S TATE expression. Methods Inferior turbinate biopsies were obtained from subjects with allerg ic rhinitis out of the allergen season. Subjects were then randomized into topical steroid- (n = 6) and placebo-treated (n = 6) groups in a double-bli nd fashion. After a 6-week treatment period, a second nasal biopsy was perf ormed 24 h after local challenge with allergen. STAT6 immunoreactivity was examined in biopsy specimens by immunocytochemistry using a specific monocl onal antibody. Numbers of inflammatory cells (CD3(+) T cells and MBP+ eosin ophils) and IL-4 mRNA(+) cells were investigated by immunocytochemistry and in situ hybridization, respectively. Results STAT6 immunoreactivity was detected in all biopsies studied and loc alized predominantly to inflammatory tissue of the nasal mucosa. After alle rgen challenge, expression of STATE was markedly increased in placebo-treat ed patients (P < 0.01). By confocal microscopy, STATE was localized to the cytoplasm and the nucleus of positively-staining cells. The allergen-induce d increase in STATE immunoreactive cells was not observed in the steroid-tr eated patients. The change in STAT6 immunoreactivity after allergen challen ge correlated significantly with the change in numbers IL-4 mRNA(+) cells ( r = 0.74. P = 0.006) and CD3(+) T cells (r = 0.76, P = 0.004), but not MBP eosinophils. Conclusion This study provides the first evidence of increased STATE expres sion in vivo in human allergic inflammation. The results support a role for STATE and IL-4 in the pathogenesis of late nasal response and show that de creases in STATE expression parallel the reduction in IL-4 expression that occurs with topical steroid treatment.