Role of IL-13Rα2 in modulating IL-13-induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa
| Autor: | Kim Thye Thong, Kai Sen Tan, Jing Liu, De Yun Wang, Heng Boon Low, Yew Kwang Ong, Li Shi, Yingying Li, Yan Yan, Yongliang Zhang, Hsiao Hui Ong, Anand Kumar Andiappan, Feng Gang Yu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male Mucin 5AC Dexamethasone 0302 clinical medicine Immunology and Allergy Nasal polyps Receptor Cells Cultured Rhinitis Interleukin-13 respiratory system Middle Aged medicine.anatomical_structure Mucociliary Clearance 030220 oncology & carcinogenesis Interleukin 13 Female Signal transduction Signal Transduction Adult medicine.medical_specialty Adolescent MAP Kinase Signaling System Immunology Statistics Nonparametric 03 medical and health sciences Young Adult Nasal Polyps Internal medicine medicine Humans Sinusitis Glucocorticoids Protein Kinase Inhibitors Flavonoids Inflammation Goblet cell business.industry medicine.disease Mucus Epithelium Nasal Mucosa 030104 developmental biology Endocrinology Interleukin-13 Receptor alpha2 Subunit business |
| Zdroj: | Allergy. 73(8) |
| ISSN: | 1398-9995 |
| Popis: | Background The IL-13 receptor α2 (IL-13Rα2) is a receptor for IL-13 which has conflicting roles in mediating IL-13 responses in the lower airway, with little known about its impact on upper airway diseases. We sought to investigate the expression of IL-13 receptors, IL-13Rα1 and IL-13Rα2, in chronically inflamed nasal epithelium, and explore IL-13-induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs). Methods The protein and mRNA expression levels of IL-13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL-13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudostratified epithelium in air-liquid interface (ALI) culture. Results There were significant increases in IL-13, IL-13Rα1, and IL-13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Rα2 (r = .5886, P = .002) but not with IL-13Rα1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Rα2 only in hNECs. IL-13 treatment induced an activation of extracellular signal-regulated kinases (ERK)1/2 and an upregulation of C-JUN, where the IL-13-induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 μmol/L) or dexamethasone (10-4 -10-7 mol/L) treatment. Conclusions IL-13Rα2 has a potential role in IL-13-induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP. |
| Databáze: | OpenAIRE |
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