Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells
Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells
复制标题
DOI：
10.1152/ajplung.00311.2001
复制
发表时间：
2002-02-01
影响因子：
4.9
通讯作者：
Poll, CT
中科院分区：
文献类型：
--
作者：
Danahay, H;Atherton, H;Poll, CT
白细胞介素（IL）-13与哮喘、过敏性鼻炎和慢性鼻窦炎相关，所有这些病症中上皮液体分泌和吸收的不平衡都可能影响疾病。我们研究了IL-13对人支气管上皮细胞在顶-空气界面培养的离子转运特性的影响。Ussing chamber研究表明，用IL-13或IL-4预处理48 h可显著降低基础短路电流（I-sc），并抑制> 98%的阿米洛利敏感电流。此外，I-SC反应增加了超过6倍和2倍以上的控制值时，分别用UTP或毛喉素刺激，细胞因子治疗后。对UTP/离子霉素的IL-13增强反应对布美他尼和DIDS敏感，并且在低氯化物、无碳酸氢盐溶液中降低。膜透性研究表明，IL-13诱导的功能性表达的顶端Ca 2+激活的阴离子电导和顶端或基底侧K+电导的变化不能占增加的I-SC响应UTP或离子霉素。结果表明，IL-13将人支气管上皮从吸收表型转化为分泌表型，这是阿米洛利敏感性电流丧失和DIDS敏感性顶端阴离子电导增加的结果。
Interleukin (IL)-13 has been associated with asthma, allergic rhinitis, and chronic sinusitis, all conditions where an imbalance in epithelial fluid secretion and absorption could impact upon the disease. We have investigated the effects of IL-13 on the ion transport characteristics of human bronchial epithelial cells cultured at an apical-air interface. Ussing chamber studies indicated that 48 h pretreatment with IL-13 or IL-4 significantly reduced the basal short-circuit current (I-sc) and inhibited the amiloride-sensitive current by >98%. Furthermore, the I-sc responses were increased by more than six- and twofold over control values when stimulated with UTP or forskolin, respectively, after cytokine treatment. The IL-13-enhanced response to UTP/ionomycin was sensitive to bumetanide and DIDS and was reduced in a low-chloride, bicarbonate-free solution. Membrane permeablization studies indicated that IL-13 induced the functional expression of an apical Ca2+-activated anion conductance and that changes in apical or basolateral K+ conductances could not account for the increased I-sc responses to UTP or ionomycin. The results indicate that IL-13 converts the human bronchial epithelium from an absorptive to a secretory phenotype that is the result of loss of amiloride-sensitive current and an increase in a DIDS-sensitive apical anion conductance.