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首页> 外文期刊>American Journal of Physiology >TGF-beta 1 downregulates CFTR expression and function in nasal polyps of non-CF patients.
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TGF-beta 1 downregulates CFTR expression and function in nasal polyps of non-CF patients.

机译：TGF-beta 1下调非CF患者鼻息肉中CFTR的表达和功能。

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Nasal polyposis is a chronic inflammatory disease of the upper airways. It has been suggested that ion transports and CFTR expression could be modified in epithelial cells from nasal polyps of non-cystic fibrosis patients. We compared human nasal epithelial cells from nasal polyps (NP) with control nasal mucosa (CM). The level of CFTR mRNA was studied by Northern blot analysis and protein expression was studied by immunoprecipitation both ex vivo and in vitro in primary cultures of human nasal epithelial cells at the air-liquid interface. Ion transports were evaluated by short-circuit measurements in vitro. CFTR gene and protein expressions were significantly decreased in NP native tissues and in culture on day 4, when a global defect of ion transports was observed in NP cultures, but not in CM. We evaluated the effect of transforming growth factor (TGF)-beta 1 on CFTR expression and function in NP cultures on day 14 and showed, for the first time, that TGF-beta 1 was able to significantly downregulatethe level of CFTR mRNA and cAMP-dependent current in NP cultures. Finally, we showed that the effects of TGF-beta 1 on ion transports could be reversed after 48-h removal of TGF-beta1 in NP cultures. In conclusion, our data strongly suggest that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression.
机译：鼻息肉病是上呼吸道的一种慢性炎性疾病。已经提出，非囊性纤维化患者鼻息肉的上皮细胞中的离子转运和CFTR表达可以被修饰。我们比较了来自鼻息肉（NP）和对照鼻黏膜（CM）的人鼻上皮细胞。通过Northern印迹分析研究了CFTR mRNA的水平，并通过气液界面处人鼻上皮细胞原代培养物中的体内和体外免疫沉淀研究了蛋白质表达。通过体外短路测量评估离子传输。在NP天然组织和培养物中，CFTR基因和蛋白质表达在第4天显着降低，而在NP培养物中却观察到了离子转运的整体缺陷，而在CM中则没有。我们在第14天评估了转化生长因子（TGF）-β1对NP培养物中CFTR表达和功能的影响，并首次表明TGF-β1能够显着下调CFTR mRNA和cAMP- NP文化中的依赖电流。最后，我们显示了在NP培养物中去除TGF-β148小时后，TGF-β1对离子转运的作用可以逆转。总之，我们的数据强烈表明，鼻息肉的慢性炎症会下调CFTR基因和蛋白质表达。

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