Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells
Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells
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DOI：
10.1152/ajplung.00344.2007
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发表时间：
2009-02-01
影响因子：
4.9
通讯作者：
Kolls, Jay K.
中科院分区：
文献类型：
--
作者：
Kreindler, James L.;Bertrand, Carol A.;Kolls, Jay K.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容白介素17A诱导正常人支气管上皮细胞分泌碳酸氢盐。Am J Physiol肺细胞分子Physiol 296：L257-L266,2009。2008年12月12日首次出版；DOI：10.1152/ajpeng.00344.2007。-人类呼吸道的先天免疫功能包括粘液纤毛清除和抗菌肽活性。这两种功能都可能受到上皮细胞离子转运变化的影响。白细胞介素17A(IL-17A)是一种T细胞细胞因子，其受体位于呼吸道上皮细胞基底膜，可促进人支气管上皮细胞分泌黏液和抗菌肽。此外，肺囊性纤维化加重期间患者的痰中IL-17A水平升高。因此，我们研究了IL-17A对成熟、分化良好的HBE细胞基础离子转运、阿米洛利敏感离子转运和Forsklin刺激离子转运的影响。将HBE单层暴露于IL-17A 48h后，除由Forsklin刺激的氯离子分泌外，还可诱导一种新的Forsklin刺激的重碳酸盐分泌，并导致极化细胞粘膜表面液体的碱化。IL-17A诱导的碳酸氢盐分泌依赖于囊性纤维化跨膜电导调节剂(CFTR)，依赖于粘膜氯离子，部分依赖于Na(+)，对浆膜抑制敏感，但对粘膜二苯乙烯抑制不敏感。这些数据表明，IL-17A调节上皮性碳酸氢盐的分泌，并暗示了囊性纤维化时呼吸道表面液体pH变化可能异常的机制。
Kreindler JL, Bertrand CA, Lee RJ, Karasic T, Aujla S, Pilewski JM, Frizzell RA, Kolls JK. Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 296: L257-L266, 2009. First published December 12, 2008; doi:10.1152/ajplung.00344.2007.-The innate immune functions of human airways include mucociliary clearance and antimicrobial peptide activity. Both functions may be affected by changes in epithelial ion transport. Interleukin-17A (IL-17A), which has a receptor at the basolateral membrane of airway epithelia, is a T cell cytokine that has been shown to increase mucus secretion and antimicrobial peptide production by human bronchial epithelial (HBE) cells. Furthermore, IL-17A levels are increased in sputum from patients during pulmonary exacerbations of cystic fibrosis. Therefore, we investigated the effects of IL-17A on basal, amiloride-sensitive, and forskolin-stimulated ion transport in mature, well-differentiated HBE cells. Exposure of HBE monolayers to IL-17A for 48 h induced a novel forskolin-stimulated bicarbonate secretion in addition to forskolin-stimulated chloride secretion and resulted in alkalinization of liquid on the mucosal surface of polarized cells. IL-17A-induced bicarbonate secretion was cystic fibrosis transmembrane conductance regulator (CFTR)-dependent, mucosal chloride-dependent, partially Na(+)-dependent, and sensitive to serosal, but not mucosal, stilbene inhibition. These data suggest that IL-17A modulates epithelial bicarbonate secretion and implicate a mechanism by which airway surface liquid pH changes may be abnormal in cystic fibrosis.