Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2025
Protease-activated receptor 2 and interleukin-13 receptor α1 activation is linked to eosinophilic chronic rhinosinusitis.
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Liao En-Chih, Lee Huai-Pao, Lee Ching-Chih
Аннотация
BACKGROUND: Protease-activated receptor 2 (PAR-2) and interleukin (IL)-13 receptor α1 (Rα1) play major roles in type 2 inflammation. However, most of the literature was limited to allergic asthma.
OBJECTIVE: To evaluate ways these receptors contribute to upper respiratory tract inflammation and to explore potential therapeutic targets in patients with eosinophilic chronic rhinosinusitis.
METHODS: Using protein interaction analysis, animal experiments, and human tissue samples, we assessed the effects of exposure to house dust mite allergen on PAR-2 and IL-13Rα1 activation and inflammatory markers, and the impact of the PAR-2 antagonist GB88. A fluorescent multiplex staining kit was used, along with specific antibodies, to label and detect proteins in the immunofluorescence tissue samples.
RESULTS: A close relationship among PAR-2 (coagulation factor II receptor-like 1), SPI-1, IL-13Rα1, and RNASE2 (eosinophil-derived neurotoxin) was noted in protein interaction analysis. House dust mite exposure significantly activated PAR-2 and IL-13Rα1 in nasal epithelial cells, leading to TH2 cytokine release (IL-25, IL-33, and thymic stromal lymphopoietin) and elevation of eosinophil proteins (eosinophil cationic protein and eosinophil-derived neurotoxin) that intensify upper respiratory tract inflammation. The PAR-2 antagonist GB88 reduced house dust mite allergen-induced PAR-2 and IL-13Rα1 expression, signal transducer and activator of transcription 6 phosphorylation, and eosinophil infiltration, and decreased inflammatory markers. PAR-2/SPI-1/IL-13Rα1 was validated in immunohistochemistry and immunofluorescence analysis of human chronic rhinosinusitis specimens.
CONCLUSION: The PAR-2/IL-13Rα1 pathway is a promising target for treating upper respiratory tract inflammation. PAR-2 inhibitors could reduce inflammation and improve the outcomes of upper respiratory tract diseases, such as eosinophilic chronic rhinosinusitis.
OBJECTIVE: To evaluate ways these receptors contribute to upper respiratory tract inflammation and to explore potential therapeutic targets in patients with eosinophilic chronic rhinosinusitis.
METHODS: Using protein interaction analysis, animal experiments, and human tissue samples, we assessed the effects of exposure to house dust mite allergen on PAR-2 and IL-13Rα1 activation and inflammatory markers, and the impact of the PAR-2 antagonist GB88. A fluorescent multiplex staining kit was used, along with specific antibodies, to label and detect proteins in the immunofluorescence tissue samples.
RESULTS: A close relationship among PAR-2 (coagulation factor II receptor-like 1), SPI-1, IL-13Rα1, and RNASE2 (eosinophil-derived neurotoxin) was noted in protein interaction analysis. House dust mite exposure significantly activated PAR-2 and IL-13Rα1 in nasal epithelial cells, leading to TH2 cytokine release (IL-25, IL-33, and thymic stromal lymphopoietin) and elevation of eosinophil proteins (eosinophil cationic protein and eosinophil-derived neurotoxin) that intensify upper respiratory tract inflammation. The PAR-2 antagonist GB88 reduced house dust mite allergen-induced PAR-2 and IL-13Rα1 expression, signal transducer and activator of transcription 6 phosphorylation, and eosinophil infiltration, and decreased inflammatory markers. PAR-2/SPI-1/IL-13Rα1 was validated in immunohistochemistry and immunofluorescence analysis of human chronic rhinosinusitis specimens.
CONCLUSION: The PAR-2/IL-13Rα1 pathway is a promising target for treating upper respiratory tract inflammation. PAR-2 inhibitors could reduce inflammation and improve the outcomes of upper respiratory tract diseases, such as eosinophilic chronic rhinosinusitis.