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Role of IL ‐13Rα2 in modulating IL ‐13‐induced MUC 5 AC and ciliary changes in healthy and CRS w NP mucosa
Author(s) -
Liu J.,
Li Y. Y.,
Andiappan A. K.,
Yan Y.,
Tan K. S.,
Ong H. H.,
Thong K. T.,
Ong Y. K.,
Yu F. G.,
Low H. B.,
Zhang Y. L.,
Shi L.,
Wang D. Y.
Publication year - 2018
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13424
Subject(s) - receptor , downregulation and upregulation , mapk/erk pathway , messenger rna , respiratory epithelium , stimulation , extracellular , signal transduction , immunology , interleukin 13 , epithelium , interleukin 8 , chemistry , dexamethasone , interleukin , cytokine , microbiology and biotechnology , biology , medicine , endocrinology , pathology , biochemistry , gene
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 ( hNEC s). 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 hNEC s 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. MUC 5 AC mRNA positively correlated with IL ‐13Rα2 ( r = .5886, P = .002) but not with IL ‐13Rα1 in primary hNEC s. IL ‐13 treatment resulted in a significant increase in mRNA and protein levels of IL ‐13Rα2 only in hNEC s. 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 hNEC s could be attenuated by ERK 1/2 inhibitor (50 μmol/L) or dexamethasone (10 −4 ‐10 −7 mol/L) treatment. Conclusions IL ‐13Rα2 has a potential role in IL ‐13‐induced MUC 5 AC and ciliary changes through ERK 1/2 signal pathway in the nasal epithelium. IL ‐13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRS w NP .