Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis.
Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis.
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DOI：
10.1016/j.jaci.2015.05.024
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Schleimer RP
中科院分区：
文献类型：
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作者：
Seshadri S;Lu X;Purkey MR;Homma T;Choi AW;Carter R;Suh L;Norton J;Harris KE;Conley DB;Kato A;Avila PC;Czarnocka B;Kopp PA;Peters AT;Grammer LC;Chandra RK;Tan BK;Liu Z;Kern RC;Schleimer RP
慢性鼻窦炎（CRS）是一种病因不明的多因素疾病，其特征是鼻窦炎症，粘液产生增加和粘膜纤毛清除缺陷。Pendrin是一种上皮阴离子转运蛋白，在哮喘和慢性阻塞性肺病中增加。Pendrin增加粘液产生并调节粘液纤毛清除。我们试图研究pendrin和粘液相关蛋白Muc 5AC在对照组和CRS患者的鼻窦组织中的表达，并评估pendrin在鼻上皮细胞（NECs）中表达的体外调节。采用实时荧光定量PCR、免疫印迹和免疫组化方法分析pendrin在鼻腔鼻窦组织中的表达和分布。分化的NECs用于研究pendrin表达的调节。在CRS患者的NP组织中观察到pendrin增加。免疫组织化学分析显示，pendrin主要局限于上皮层。Pendrin表达与炎症细胞标志物显著相关，表明这些细胞产生的因子可能诱导pendrin表达。此外，pendrin和periostin（哮喘中的生物标志物）与IL-13相关，表明pendrin可能由鼻窦组织中的这种细胞因子诱导。粘液组分蛋白Muc 5AC与pendrin弱相关，表明pendrin可能调节NP中的粘液产生。在培养的NECs中，pendrin表达由Th 2细胞因子诱导，并且当Th 2细胞因子与IL-17 A组合时协同诱导。有趣的是，人鼻病毒对IL-13诱导的pendrin表达具有增强作用。地塞米松抑制pendrin表达，表明地塞米松对哮喘和CRS的治疗益处可能涉及pendrin表达的调节。Th 2介导的pendrin表达在CRS患者的鼻息肉中增加，并可能导致炎症增加、粘液产生和粘膜纤毛清除减少。
Chronic rhinosinusitis (CRS) is a multifactorial disease of unknown etiology characterized by sinonasal inflammation, increased mucus production and defective mucociliary clearance. Pendrin, an epithelial anion transporter, is increased in asthma and chronic obstructive pulmonary disease. Pendrin increases mucus production and regulates mucociliary clearance. We sought to investigate the expression of pendrin and the mucus-related protein Muc5AC in sinonasal tissues of control and CRS patients, and to evaluate the regulation of pendrin expression in nasal epithelial cells (NECs) in vitro. The expression and distribution of pendrin in sinonasal tissues was analyzed using real-time PCR, immunoblot analysis and immunohistochemistry. Differentiated NECs were used to study the regulation of pendrin expression. Increased pendrin was observed in NP tissue of CRS patients. Immunohistochemistry analysis revealed that pendrin was largely restricted to the epithelial layer. Pendrin expression significantly correlated with inflammatory cell markers, suggesting that the factors made by these cells may induce pendrin expression. Furthermore, both pendrin and periostin (a biomarker in asthma) correlated with IL-13, suggesting that pendrin may be induced by this cytokine in sinonasal tissues. The mucus component protein Muc5AC, correlated weakly with pendrin, indicating that pendrin might modulate mucus production in NPs. In cultured NECs, pendrin expression was induced by Th2 cytokines and was induced synergistically when Th2 cytokines were combined with IL-17A. Interestingly, human rhinovirus had a potentiating effect on IL-13 induced pendrin expression. Dexamethasone suppressed pendrin expression suggesting that the therapeutic benefit of dexamethasone in asthma and CRS may involve regulation of pendrin expression. Th2-mediated pendrin expression is increased in nasal polyps of patients with CRS and may lead to increased inflammation, mucus production and a decreased mucociliary clearance.