Bathoorn Erik, Daly Paul, Gaiser Birgit, Sternad Karl, Poland Craig, Macnee William, Drost Ellen M
ELEGI, Colt Research Laboratories, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH 16 4TJ, UK.
Int J Inflam. 2011;2011:569416. doi: 10.4061/2011/569416. Epub 2011 Jul 12.
Introduction. Gastroesophageal reflux has been associated with chronic inflammatory diseases and may be a cause of airway remodelling. Aspiration of gastric fluids may cause damage to airway epithelial cells, not only because acidity is toxic to bronchial epithelial cells, but also since it contains digestive enzymes, such as pepsin. Aim. To study whether pepsin enhances cytotoxicity and inflammation in airway epithelial cells, and whether this is pH-dependent. Methods. Human bronchial epithelial cells were exposed to increasing pepsin concentrations in varying acidic milieus, and cell proliferation and cytokine release were assessed. Results. Cell survival was decreased by pepsin exposure depending on its concentration (F = 17.4) and pH level of the medium (F = 6.5) (both P < 0.01). Pepsin-induced interleukin-8 release was greater at lower pH (F = 5.1; P < 0.01). Interleukin-6 induction by pepsin was greater at pH 1.5 compared to pH 2.5 (mean difference 434%; P = 0.03). Conclusion. Pepsin is cytotoxic to bronchial epithelial cells and induces inflammation in addition to acid alone, dependent on the level of acidity. Future studies should assess whether chronic aspiration causes airway remodelling in chronic inflammatory lung diseases.
引言。胃食管反流与慢性炎症性疾病有关，可能是气道重塑的一个原因。胃液的误吸可能会对气道上皮细胞造成损害，这不仅是因为酸性物质对支气管上皮细胞有毒性，还因为它含有消化酶，如胃蛋白酶。目的。研究胃蛋白酶是否会增强气道上皮细胞的细胞毒性和炎症反应，以及这是否依赖于pH值。方法。将人支气管上皮细胞暴露于不同酸性环境中逐渐增加的胃蛋白酶浓度下，评估细胞增殖和细胞因子释放情况。结果。胃蛋白酶暴露会导致细胞存活率下降，这取决于其浓度（F = 17.4）和培养基的pH值水平（F = 6.5）（两者P < 0.01）。在较低pH值下，胃蛋白酶诱导的白细胞介素-8释放量更大（F = 5.1；P < 0.01）。与pH 2.5相比，在pH 1.5时胃蛋白酶诱导的白细胞介素-6水平更高（平均差异434%；P = 0.03）。结论。胃蛋白酶对支气管上皮细胞具有细胞毒性，除了单独的酸性物质外还会诱导炎症反应，这取决于酸度水平。未来的研究应评估慢性误吸是否会导致慢性炎症性肺部疾病中的气道重塑。
