Hackett A P, Trinick R E, Rose K, Flanagan B F, McNamara P S
Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Alder Hey Children's Hospital NHS Foundation Trust, Eaton Rd, Liverpool, UK.
Respir Res. 2016 Jul 15;17(1):82. doi: 10.1186/s12931-016-0399-3.
Aspiration lung disease (ALD) is a common cause of respiratory morbidity in children and adults with severe neurodisability (sND). Recent studies suggest that chronic microaspiration of gastric contents is associated with mild rather than low, airway acidification. We investigated inflammatory responses to infection by airway epithelial cells (AECs) exposed to weakly acidic media.
Using pH measurements from children with sND at high risk of ALD as a guide, we incubated AECs in weakly acidic (pH5.5-7.4) media alone; in combination with lipopolysaccharide (LPS); or prior to LPS stimulation at normal pH. Interleukin (IL) -6 and IL-8 expression were measured.
IL-6/8 expression in AECs simultaneously exposed to weakly acidic media and LPS for 4 h was reduced with no effect on cell viability. Pre-incubation of AECs at weakly acidic pH also reduced subsequent LPS-induced cytokine expression. Suppression of inflammation was greatest at lower pHs (pH 5.5-6.0) for prolonged periods (16/24 h), but this also adversely affected cell viability.
AEC inflammatory responses to bacterial stimuli is markedly reduced in a mildly acidic environment.
误吸性肺病(ALD)是患有严重神经功能障碍(sND)的儿童和成人呼吸疾病的常见病因。最近的研究表明,胃内容物的慢性微量误吸与气道酸化程度较轻而非较低有关。我们研究了暴露于弱酸性介质中的气道上皮细胞(AEC)对感染的炎症反应。
以患ALD高风险的sND儿童的pH测量值为指导,我们将AEC单独置于弱酸性(pH5.5 - 7.4)介质中培养;与脂多糖(LPS)联合培养;或在正常pH下于LPS刺激之前培养。测量白细胞介素(IL)-6和IL-8的表达。
AEC同时暴露于弱酸性介质和LPS 4小时后,IL-6/8表达降低,且对细胞活力无影响。在弱酸性pH下对AEC进行预培养也降低了随后LPS诱导的细胞因子表达。在较低pH值(pH 5.5 - 6.0)下长时间(16/24小时)炎症抑制作用最大,但这也对细胞活力产生了不利影响。
在轻度酸性环境中,AEC对细菌刺激的炎症反应明显降低。