Naderi Nafiseh, Farias Raquel, Abou Rjeili Mira, Mostafavi-Pour-Manshadi Seyed-Mohammad-Yousof, Krishnan Suurya, Li Pei Zhi, Baglole Carolyn J, Bourbeau Jean
Respiratory Epidemiology and Clinical Research Unit, Research Institute of McGill University Health Center, McGill University, Montréal, Canada.
Snyder Institute for Chronic Diseases, Department of Critical Care Medicine, University of Calgary, Calgary, Canada.
Exp Lung Res. 2021 Feb-Mar;47(2):98-109. doi: 10.1080/01902148.2020.1857470. Epub 2020 Dec 18.
Macrolide therapy is effective in reducing chronic obstructive pulmonary disease (COPD) exacerbations. Our recent study has shown the effectiveness of taking azithromycin in COPD patients, not only ex-smokers but also current smokers. Beyond their anti-microbial effects, macrolides have anti-inflammatory and immunomodulatory properties. The aim of this study was to determine if pretreatment with azithromycin modulates cigarette smoke-induced inflammation in airway epithelial cells. We hypothesized that pretreatment with azithromycin decreases exacerbation frequency by modulating inflammation in human airway epithelial cells exposed to cigarette smoke. BEAS-2B bronchial epithelial cells were incubated with 5% cigarette smoke extract (CSE) for 3 h, 6 h, and 24 h. Then, airway epithelial cells were pretreated with azithromycin and exposed to 5% CSE. In each stage, the expression and release of IL-6 and IL-8 mRNA were analyzed by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. There was a significant increase of IL-6 and IL-8 mRNA, as well as an increase in extracellular IL-8 protein following exposure to 5% CSE. When cells were pretreated with azithromycin and exposed to 5% CSE for 3 h, there was a significant dose-dependent decrease in the expression of IL-6 mRNA. A final concentration of 9 µg/mL of azithromycin was sufficient to decrease IL-6, IL-8 mRNA, and extracellular IL-8 levels. Pretreatment with azithromycin decreased the expression of IL-6 and IL-8 mRNA and the release of IL-8 in bronchial epithelial cells exposed to cigarette smoke. These results demonstrate the direct effect of azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke.
大环内酯类药物治疗在减少慢性阻塞性肺疾病（COPD）急性加重方面有效。我们最近的研究表明，服用阿奇霉素对COPD患者有效，不仅对既往吸烟者有效，对当前吸烟者也有效。除了抗菌作用外，大环内酯类药物还具有抗炎和免疫调节特性。本研究的目的是确定阿奇霉素预处理是否能调节香烟烟雾诱导的气道上皮细胞炎症。我们假设阿奇霉素预处理通过调节暴露于香烟烟雾的人气道上皮细胞中的炎症来降低急性加重频率。BEAS-2B支气管上皮细胞与5%香烟烟雾提取物（CSE）孵育3小时、6小时和24小时。然后，气道上皮细胞用阿奇霉素预处理并暴露于5% CSE。在每个阶段，分别通过定量实时PCR（qRT-PCR）和酶联免疫吸附测定（ELISA）分析IL-6和IL-8 mRNA的表达和释放。暴露于5% CSE后，IL-6和IL-8 mRNA显著增加，细胞外IL-8蛋白也增加。当细胞用阿奇霉素预处理并暴露于5% CSE 3小时时，IL-6 mRNA的表达有显著的剂量依赖性降低。阿奇霉素的最终浓度为9μg/mL足以降低IL-6、IL-8 mRNA和细胞外IL-8水平。阿奇霉素预处理降低了暴露于香烟烟雾的支气管上皮细胞中IL-6和IL-8 mRNA的表达以及IL-8的释放。这些结果证明了阿奇霉素对暴露于香烟烟雾的支气管上皮细胞中炎症介质的直接作用。
