Inhibition of IL-13-induced periostin in airway epithelium attenuates cellular protein expression of MUC5AC
Inhibition of IL-13-induced periostin in airway epithelium attenuates cellular protein expression of MUC5AC
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DOI：
10.1111/resp.12873
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发表时间：
2017-01-01
期刊：
影响因子：
6.9
通讯作者：
Rubin, Bruce K.
中科院分区：
文献类型：
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作者：
Suzaki, Isao;Kawano, Shuichi;Rubin, Bruce K.
背景与目的哮喘患者血清骨膜蛋白升高，可作为肺IL-13活性的替代标志物。血清骨膜素水平是预测抗il -13药物lebrikizumab有利反应的最可靠的生物标志物。我们研究了IL-13刺激骨膜蛋白的机制、骨膜蛋白的极化分泌以及骨膜蛋白是否会直接影响气道细胞的粘蛋白分泌。方法将正常人支气管上皮细胞（NHBE）在IL-13存在的气液界面（ALI）下培养，观察特异性抑制剂来氟米特（Janus kinase， JAK）/信号转导和转录因子6 （STAT6）抑制剂)或PD98059 （MEK/细胞外调节蛋白激酶（extracellular regulated protein kinase， ERK）抑制剂）对骨膜蛋白生成的影响。我们检测了暴露于重组人（rh）骨膜蛋白或IL-13的NHBE细胞在存在和不存在OC-20（一种骨膜蛋白中和抗体）的情况下MUC5AC的分泌情况。结果IL-13诱导的骨膜蛋白主要向细胞基底表面分泌。杯状细胞比纤毛细胞产生更多的骨膜蛋白(P
Background and objectiveSerum periostin is increased in asthma and serves as a surrogate marker for IL-13 activity in the lung. Serum levels of periostin are the most robust biomarker predicting a favourable response to the anti-IL-13 drug, lebrikizumab. We investigated the mechanisms of IL-13 stimulation of periostin, the polarized secretion of periostin and whether periostin would have a direct effect on mucin secretion by airway cells.MethodsNormal human bronchial epithelial (NHBE) cells were cultured at air-liquid interface (ALI) in the presence of IL-13, and we evaluated the effect of the specific inhibitors, leflunomide (Janus kinase (JAK)/signal transducer and activator of transcription factor 6 (STAT6) inhibitor) or PD98059 (MEK/extracellular regulated protein kinase (ERK) inhibitor), on periostin production. We examined MUC5AC secretion from NHBE cells exposed to recombinant human (rh) periostin or IL-13 in the presence and absence of OC-20, a periostin-neutralizing antibody.Results IL-13 induced periostin protein which was predominantly secreted towards the basal surface of the cells. Periostin production was much greater from goblet cells than ciliated cells (P