Aldallal Nada, McNaughton Erin E, Manzel Lori J, Richards Autumn M, Zabner Joseph, Ferkol Thomas W, Look Dwight C
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Am J Respir Crit Care Med. 2002 Nov 1;166(9):1248-56. doi: 10.1164/rccm.200206-627OC.
The concept that inflammatory gene expression is dysregulated in airway epithelial cells from patients with cystic fibrosis (CF) is controversial. To examine this possibility systematically, responses to inflammatory stimuli were compared in CF airway epithelial cell lines without versus with wild-type CF transmembrane conductance regulator (CFTR) complementation and in tracheobronchial epithelial cells from patients with versus without CF. Epithelial cell expression of the leukocyte adhesion glycoprotein intercellular adhesion molecule-1 (ICAM-1) and release of the neutrophil chemoattractant interleukin (IL)-8 were determined under basal conditions or after exposure to stimuli important in CF airway inflammatory responses. We found that uncorrected CF airway epithelial cell lines inconsistently expressed higher ICAM-1 and IL-8 levels. Human CF tracheobronchial epithelial cells in primary culture released moderately increased IL-8 only after exposure to Pseudomonas aeruginosa. In CF cells with higher IL-8 release, transient expression of wild-type CFTR using an adenoviral vector did not specifically affect cytokine levels. The results indicate that there is considerable variability in airway epithelial cell responses to inflammatory stimuli among different individuals and cell models systems. Although increased ICAM-1 and IL-8 expression are observed in some CF airway epithelial cell models, many CF cells do not exhibit significant dysregulation of these important inflammatory genes.
囊性纤维化（CF）患者气道上皮细胞中炎症基因表达失调这一概念存在争议。为了系统地研究这种可能性，我们比较了有无野生型CF跨膜传导调节因子（CFTR）互补的CF气道上皮细胞系对炎症刺激的反应，以及有和没有CF的患者的气管支气管上皮细胞对炎症刺激的反应。在基础条件下或暴露于CF气道炎症反应中重要的刺激后，测定白细胞粘附糖蛋白细胞间粘附分子-1（ICAM-1）的上皮细胞表达和中性粒细胞趋化因子白细胞介素（IL）-8的释放。我们发现未经校正的CF气道上皮细胞系ICAM-1和IL-8水平表达不一致且较高。原代培养的人CF气管支气管上皮细胞仅在暴露于铜绿假单胞菌后才适度增加IL-8的释放。在IL-8释放较高的CF细胞中，使用腺病毒载体瞬时表达野生型CFTR并没有特异性影响细胞因子水平。结果表明，在不同个体和细胞模型系统中，气道上皮细胞对炎症刺激的反应存在很大差异。虽然在一些CF气道上皮细胞模型中观察到ICAM-1和IL-8表达增加，但许多CF细胞并未表现出这些重要炎症基因的明显失调。
