支气管肺泡灌洗
内分泌学
内科学
医学
哮喘
上皮
免疫学
呼吸上皮
卵清蛋白
炎症
肺
病理
免疫系统
作者
Jiayan Xu,Yaqi Meng,Man Jia,Jie Jiang,Yi Yang,Yingwei Ou,Yunhui Wu,Xiaoyi Yan,Mao Huang,Ian M. Adcock,Xin Yao
出处
期刊:Allergy
[Wiley]
日期:2021-06-03
卷期号:76 (8): 2475-2487
被引量:12
摘要
Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and airway remodeling. Airway hyperresponsiveness results from enhanced airway smooth muscle (ASM) contraction potentially under the control of an epithelium-derived relaxing factor (EpDRF). However, relatively rare is known about EpDRF. We aimed to elucidate the role of epithelium-derived stanniocalcin-1 (STC1) on AHR and ASM contraction.Stanniocalcin-1 levels in the serum of asthmatic patients and healthy volunteers and in bronchoalveolar lavage fluid (BALF) from ovalbumin (OVA)-challenged mice were measured by ELISA. The effects of exogenous STC1 on AHR and on inflammation were examined in mice. IL-13 modulation of STC1 mRNA and protein levels was studied in human bronchial epithelial cell lines (16HBE). The function of STC1 on Ca2+ influx and ASM contraction was examined ex vivo.Serum STC1 was decreased in asthma (n = 93) compared with healthy volunteers (1071 ± 30.4 vs 1414 ± 75.1 pg/ml, p < 0.0001, n = 23) and correlated with asthma control (p = 0.0270), lung function (FEV1, p = 0.0130), and serum IL-13 levels (p = 0.0009). Treatment of ten asthmatic subjects with inhaled corticosteroids/long-acting beta2-agonists (ICS/LABA) for 1 year enhanced STC1 expression which correlated with improved asthma control (p = 0.022). STC1 was mainly expressed in bronchial epithelium and intranasal administration of recombinant human STC1 (rhSTC1) reduced AHR and inflammation in mice. IL-13 suppressed STC1 release from 16HBE, whereas rhSTC1 blocked store-operated Ca2+ entry (SOCE) by suppressing stromal interaction molecule 1 (STIM1) and further inhibited ASM cell contractility by suppressing Ca2+ -dependent myosin light chain (MLC) phosphorylation.Our data indicate that STC1 deficiency in asthmatic airways promotes STIM1 hyperactivity, enhanced ASM contraction, and AHR. STC1 may be a candidate EpDRF.
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