Galietta Luis J V, Pagesy Patrick, Folli Chiara, Caci Emanuela, Romio Leila, Costes Bruno, Nicolis Elena, Cabrini Giulio, Goossens Michel, Ravazzolo Roberto, Zegarra-Moran Olga
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova, Italy.
J Immunol. 2002 Jan 15;168(2):839-45. doi: 10.4049/jimmunol.168.2.839.
Recent data show that proinflammatory stimuli may modify significantly ion transport in the airway epithelium and therefore the properties of the airway surface fluid. We have studied the effect of IL-4, a cytokine involved in the pathogenesis of asthma, on transepithelial ion transport in the human bronchial epithelium in vitro. Incubation of polarized bronchial epithelial cells with IL-4 for 6-48 h causes a marked inhibition of the amiloride-sensitive Na(+) channel as measured in short circuit current experiments. On the other hand, IL-4 evokes a 2-fold increase in the current activated by a cAMP analog, which reflects the activity of the cystic fibrosis transmembrane conductance regulator (CFTR). Similarly, IL-4 enhances the response to apical UTP, an agonist that activates Ca(2+)-dependent Cl(-) channels. These effects are mimicked by IL-13 and blocked by an antagonist of IL-4Ralpha. RT-PCR experiments show that IL-4 elicits a 7-fold decrease in the level of the gamma amiloride-sensitive Na(+) channel mRNA, one of the subunits of the amiloride-sensitive Na(+) channel, and an increase in CFTR mRNA. Our data suggest that IL-4 may favor the hydration of the airway surface by decreasing Na(+) absorption and increasing Cl(-) secretion. This could be required to fluidify the mucus, which is hypersecreted during inflammatory conditions. On the other hand, the modifications of ion transport could also affect the ion composition of airway surface fluid.
最近的数据表明，促炎刺激可能会显著改变气道上皮中的离子转运，进而影响气道表面液体的性质。我们研究了白细胞介素-4（IL-4）这种参与哮喘发病机制的细胞因子对人支气管上皮细胞跨上皮离子转运的影响。在短路电流实验中，用IL-4孵育极化的支气管上皮细胞6至48小时，会导致对氨氯地平敏感的Na(+)通道受到显著抑制。另一方面，IL-4可使由环磷酸腺苷（cAMP）类似物激活的电流增加两倍，这反映了囊性纤维化跨膜电导调节因子（CFTR）的活性。同样，IL-4增强了对顶端尿苷三磷酸（UTP）的反应，UTP是一种激活钙依赖性Cl(-)通道的激动剂。这些效应可被IL-13模拟，并被IL-4Rα拮抗剂阻断。逆转录聚合酶链反应（RT-PCR）实验表明，IL-4可使氨氯地平敏感的Na(+)通道mRNA（氨氯地平敏感的Na(+)通道的亚基之一）水平降低7倍，并使CFTR mRNA增加。我们的数据表明，IL-4可能通过减少Na(+)吸收和增加Cl(-)分泌来促进气道表面的水合作用。这可能是使炎症状态下分泌过多的黏液液化所必需的。另一方面，离子转运的改变也可能影响气道表面液体的离子组成。
