Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease
Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease
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DOI：
10.4049/jimmunol.180.9.6262
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Izuhara, Kenji
中科院分区：
文献类型：
--
作者：
Nakao, Isao;Kanaji, Sachiko;Izuhara, Kenji
气道粘液的过量产生是支气管哮喘和慢性阻塞性肺病（COPD）的主要特征，并导致这些疾病的发病率和死亡率。IL-13是一种Th 2型细胞因子，是支气管哮喘发病机制中的中心介质，包括粘液过度产生。使用全基因组搜索气道上皮细胞中响应于IL-13诱导的基因，我们鉴定了由SLC 26 A4（PDS）基因编码的pendrin作为负责气道粘液产生的分子。在哮喘和COPD小鼠模型中，pendrin在气道上皮细胞的顶侧上调，与粘液过度产生相关。Pendrin诱导气道上皮细胞中MUC 5AC（哮喘和COPI中粘液的主要产物）的表达。最后，使用仙台病毒载体在体内气道上皮细胞中强制表达pendrin，快速诱导小鼠肺腔中粘液过度产生以及嗜中性粒细胞浸润。这些发现共同表明，pendrin可以诱导气道上皮细胞中的粘液产生，并可能是支气管哮喘和COPD的治疗靶点候选者。
Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPI), in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with nentrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD.