Alternaria Induces Production of Thymic Stromal Lymphopoietin in Nasal Fibroblasts Through Toll-like Receptor 2

ABSTRACT

PURPOSE: Chronic rhinosinusitis with nasal polyps is a chronic inflammatory disease with markedly increased eosinophils, Th2-type lymphocytes, fibroblasts, and goblet cells. Fungi are commonly associated with airway inflammatory diseases, and thymic stromal lymphopoietin (TSLP) is important in the development of Th2 inflammatory responses. The aim of this study was to investigate the interaction between airborne fungi and nasal fibroblasts in TSLP mRNA and protein expression. METHODS: Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria and Aspergillus, respectively, for 48 hours, and TSLP mRNA and protein expressions were measured. The reverse transcriptase polymerase chain reaction was performed for the Toll-like receptor (TLR) mRNA expression of the nasal fibroblasts. To determine the role of TLR in the induction of TSLP, the fibroblasts were transfected with siRNA against TLR2 and TLR5. RESULTS: Alternaria induced TSLP mRNA and protein expression in both inferior turbinate and nasal polyp fibroblasts. The nasal polyp fibroblasts responded more strongly to the fungi. TLR2 and TLR5 mRNA expressions were significantly increased with fungal stimulation and TSLP production was significantly inhibited by siRNA against TLR2. CONCLUSIONS: The results of this study show that TSLP expression could be induced in nasal fibroblasts by exposure to Alternaria and that TLR2 may be involved in the process. The promotion of TSLP production in nasal fibroblasts by airborne fungi may facilitate the development or exacerbation of Th2-type nasal inflammation, especially in CRS with nasal polyps.