标题: Role of IL-13Ralpha2 in modulating IL-13 induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa.
作者: Liu, Jing; Li, YingYing; Andiappan, Anand Kumar; Yan, Yan; Kai Sen, Tan; Ong, Hsiao Hui; Thong, Kim Thye; Ong, Yew Kwang; Yu, Feng Gang; Low, Heng Bo 更多
作者机构:[ Liu, Jing; Liu J] Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.;[ Li, YingYing; Li Y] 更多
来源: Allergy
出版年:2018
DOI:10.1111/all.13424
摘要: BACKGROUND: The IL-13 receptor alpha2 (IL-13Ralpha2) 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-13Ralpha1 and IL-13Ralpha2, 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-13Ralpha1 and IL-13Ralpha2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Ralpha2 (r=0.5886, p=0.002) but not with IL-13Ralpha1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Ralpha2 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 muMol/L) or dexamethasone (10(-4) -10(-7) Mol/L) treatment. CONCLUSIONS: IL-13Ralpha2 has a potential role in IL-13 induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Ralpha2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP. This article is protected by copyright. All rights reserved.
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