Respiratory syncytial virus persistent infection causes acquired CFTR dysfunction in human bronchial epithelial cells. / å‘¼å¸é“åˆèƒžç— æ¯’æŒç»­æ„ŸæŸ“å¯¼è‡´äººæ”¯æ°”ç®¡ä¸Šçš®ç»†èƒžå›Šæ€§çº¤ç»´åŒ–ç©¿è†œä¼ å¯¼è°ƒèŠ‚è›‹ç™½åŠŸèƒ½éšœç¢.

OBJECTIVES: Many studies have shown that respiratory syncytial virus persistent infection may be the main cause of chronic respiratory pathology.However, the mechanism is unclear. Cystic fibrosis transmembrane conduction regulator (CFTR) is an apical membrane chloride channel, which is very important for the regulation of epithelial fluid, chloride ion, and bicarbonate transport. CFTR dysfunction will lead to changes in bronchial secretions and impair mucus clearance, which is related to airway inflammation. In our previous study, we observed the down-regulation of CFTR in airway epithelial cells in respiratory syncytial virus (RSV) infected mouse model. In this study, we further investigated the expression and function of CFTR by constructing an airway epithelial cell model of RSV persistent infection. METHODS: 16HBE14o- cells were infected with RSV at 0.01 multiplicity of infection (MOI). The expression of CFTR was detected by real-time RT-PCR, immunofluorescence, and Western blotting. The intracellular chloride concentration was measured by N-(ethoxycarbonylmethyl)-6-methoxyquinolium bromide (MQAE) and the chloride current was measured by whole-cell patch clamp recording. RESULTS: 16HBE14o- cells infected with RSV were survived to successive passages of the third generation (G3), while the expression and function of CFTR was progressively decreased upon RSV infection from the first generation (G1) to G3. Exposure of 16HBE14o- cells to RSV led to the gradual increase of TGF-ß1 as well as phosphorylation of Smad2 following progressive RSV infection. Disruption of TGF-ß1 signaling by SB431542 prevented Smad2 phosphorylation and rescued the expression of CFTR. CONCLUSIONS: RSV infection can lead to defective CFTR function in airway epithelial cells, which may be mediated via activation of TGF-ß1 signaling pathway.