Role of IL-13Rα2 in modulating IL-13 induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa

Abstract

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 pseudo-stratified 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=0.5886, p=0.002) 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.

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