Corr4A和VRT325不会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。
Corr4A and VRT325 do not reduce the inflammatory response to P. aeruginosa in human cystic fibrosis airway epithelial cells.
作者信息
Talebian Laleh, Coutermarsh Bonita, Channon Jacqueline Y, Stanton Bruce A
机构信息
Department of Physiology, Dartmouth Medical School, Hanover, Germany.
出版信息
Cell Physiol Biochem. 2009;23(1-3):199-204. doi: 10.1159/000204108. Epub 2009 Feb 18.
Abstract
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 DeltaF508-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 DeltaF508-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 DeltaF508-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.
摘要
背景
铜绿假单胞菌长期定植于囊性纤维化（CF）患者的肺部并引发促炎反应。CF气道中的细胞因铜绿假单胞菌感染而过度分泌白细胞介素-6（IL-6）和白细胞介素-8（IL-8），这被认为会导致肺损伤。因此，本研究的目的是验证以下假设：Corr4a和VRT325（这两种研究性化合物可增加人CF气道细胞中DeltaF508-CFTR介导的氯离子分泌）可减轻对铜绿假单胞菌的促炎反应。
方法
通过多重分析测量极化的CF人气道上皮细胞（CFBE41o-）分泌IL-6和IL-8的情况，并在尤斯灌流小室中测量DeltaF508-CFTR氯离子分泌。将气道细胞暴露于铜绿假单胞菌（PAO1或PA14）以及Corr4a或VRT325中。
结果
Corr4a和VRT325增加了DeltaF508-CFTR氯离子分泌，但并未降低基础状态下IL-6或IL-8的分泌，也未降低由铜绿假单胞菌（PA14或PAO1）刺激引起的IL-6和IL-8分泌。
结论
Corr4a和VRT325不会减轻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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2
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3
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4
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