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Corr4A and VRT325 do not Reduce the Inflammatory Response to P. aeruginosa in Human Cystic Fibrosis Airway Epithelial Cells

机译:Corr4A和VRT325不会减少人囊性纤维化气道上皮细胞对铜绿假单胞菌的炎症反应

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Background: P. aeruginosa chronically colonizes the lung in CF patients and elicits a proinflammatory response. Excessive secretion of IL-6 and IL-8 by CF airway cells in response to P. aeruginosa infection in the CF airway is though to contribute to lung injury. Accordingly, the goal of this study was to test the hypothesis that Corr4a and VRT325, investigational compounds that increase Delta F508-CFTR mediated Cl(-)secretion in human CF airway cells, reduce the pro-inflammatory response to P. aeruginosa. Methods: IL-6 and IL-8 secretion by polarized CF human airway epithelial cells (CFBE41o-) were measured by multiplex analysis, and Delta F508-CFTR Cl- secretion was measured in Ussing chambers. Airway cells were exposed to P. aeruginosa (PAO1 or PA14) and Corr4a or VRT325. Results: Corr4a and VRT325 increased Delta F508-CFTR Cl- secretion but did not reduce either constitutive IL-6 or IL-8 secretion, or IL-6 and IL-8 secretion stimulated by P. aeruginosa (PA14 or PAO1). Conclusions: Corr4a and VRT325 do not reduce the inflammatory response to P. aeruginosa in human cystic fibrosis airway epithelial cells.
机译:背景:铜绿假单胞菌在CF患者中长期定居在肺部并引发促炎反应。 CF气道细胞对CF气道中的铜绿假单胞菌感染作出了过度分泌的IL-6和IL-8分泌,但这是造成肺损伤的原因。因此,本研究的目的是检验以下假设:Corr4a和VRT325是增加Delta F508-CFTR介导的人CF气道细胞Cl(-)分泌的研究化合物,可减少对铜绿假单胞菌的促炎反应。方法:通过多重分析测定极化的CF人气道上皮细胞(CFBE410o-)的IL-6和IL-8分泌,并在Ussings室中测定Delta F508-CFTR Cl-分泌。气道细胞暴露于铜绿假单胞菌(PAO1或PA14)和Corr4a或VRT325。结果:Corr4a和VRT325增加了Delta F508-CFTR Cl-分泌,但没有减少组成型IL-6或IL-8分泌,或铜绿假单胞菌(PA14或PAO1)刺激的IL-6和IL-8分泌。结论:Corr4a和VRT325不能降低人囊性纤维化气道上皮细胞对铜绿假单胞菌的炎症反应。

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