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首页> 外文期刊>American Journal of Physiology >Activation of NF-kappaB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function.
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Activation of NF-kappaB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function.

机译：气道上皮细胞中NF-κB的激活取决于CFTR转运和Cl通道功能。

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摘要

Polymorphonuclear leukocyte-dominated airway inflammation is a major component of cystic fibrosis (CF) lung disease and may be associated with CF transmembrane conductance regulator (CFTR) dysfunction as well as infection. Mutant DeltaF508 CFTR is mistrafficked, accumulates in the endoplasmic reticulum (ER), and may cause "cell stress" and activation of nuclear factor (NF)-kappaB. G551D mutants also lack Cl- channel function, but CFTR is trafficked normally. We compared the effects of CFTR mutations on the endogenous activation of an NF-kappaB reporter construct. In transfected Chinese hamster ovary cells, the mistrafficked DeltaF508 allele caused a sevenfold activation of NF-kappaB compared with wild-type CFTR or the G551D mutant (P < 0.001). NF-kappaB was also activated in 9/HTEo-/pCep-R cells and in 16HBE/pcftr antisense cell lines, which lack CFTR Cl- channel function but do not accumulate mutant protein in the ER. This endogenous activation of NF-kappaB was associated with elevated interleukin-8 expression. Impaired CFTR Cl- channel activity as well as cell stress due to accumulation of mistrafficked CFTR in the ER contributes to the endogenous activation of NF-kappaB in cells with the CFTR mutation.
机译：多形核白细胞为主的气道炎症是囊性纤维化（CF）肺部疾病的主要成分，可能与CF跨膜电导调节剂（CFTR）功能障碍以及感染有关。突变的DeltaF508 CFTR错配，累积在内质网（ER）中，并可能引起“细胞应激”和核因子（NF）-κB的激活。 G551D突变体也缺乏Cl通道功能，但CFTR正常贩运。我们比较了CFTR突变对NF-κB报告基因构建体的内源性激活的影响。与野生型CFTR或G551D突变体相比，在转染的中国仓鼠卵巢细胞中，迷路的DeltaF508等位基因引起了NF-κB的七倍活化（P <0.001）。 NF-κB在9 / HTEo- / pCep-R细胞和16HBE / pcftr反义细胞系中也被激活，它们缺乏CFTR Cl-通道功能，但在ER中不积累突变蛋白。 NF-κB的这种内源性激活与白介素8表达升高有关。 CFTR Cl-通道活性受损，以及由于ER错配的CFTR积累导致的细胞应激，导致CFTR突变的细胞内NF-κB内源性活化。

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