Background: Macrolides have anti-inflammatory and antioxidative stress function, but their pharmacological regulation remains unclear. Sirtuin 1 (SIRT1) is redox-sensitive protein belongs to class III histone/protein deacetylases, SIRT1 regulates the acetylation/expression of nuclear factor κB (NF-κB) and is involved in the airway inflammation of chronic obstructive pulmonary disease. Objectives: The present study was designed to examine the effects of erythromycin (EM) on the SIRT1-NF-κB axis and NF-κB-dependent proinflammatory cytokines. Methods: Human macrophages were preincubated with EM and then treated with cigarette smoke extract (CSE). The mice were treated by injecting drugs to gastric with EM before cigarette smoke exposure. Reactive oxygen species (ROS) released by treated human macrophages were detected using flow cytometry. The expression of SIRT1 and NF-κB was analyzed by western blotting. SIRT1 and the RelA/p65 subunits of NF-κB interaction were detected by coimmunoprecipitation. We found that EM suppressed CSE-induced ROS released in human macrophages, which coincided with increases in SIRT1 protein expression in the macrophages and lungs of mice, resulting in suppressed NF-κB acetylation and expression correlated with a reduction of inflammatory mediators. Conclusion: These findings suggest that EM increased SIRT1, leading to acetylation/expression of NF-κB, and thereby decreasing cigarette smoke-driven NF-κB-dependent proinflammatory cytokine.

中文翻译：

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红霉素通过巨噬细胞和小鼠肺中的 Sirtuin 1-核因子 κB 轴调节香烟烟雾诱导的促炎介质释放

背景：大环内酯类具有抗炎和抗氧化应激作用，但其药理调控尚不清楚。Sirtuin 1 (SIRT1) 是氧化还原敏感蛋白，属于 III 类组蛋白/蛋白质脱乙酰酶，SIRT1 调节核因子 κB (NF-κB) 的乙酰化/表达，并参与慢性阻塞性肺疾病的气道炎症。目的：本研究旨在检查红霉素 (EM) 对 SIRT1-NF-κB 轴和 NF-κB 依赖性促炎细胞因子的影响。方法：人类巨噬细胞用 EM 预培养，然后用香烟烟雾提取物 (CSE) 处理。在暴露于香烟烟雾之前，通过用 EM 向胃注射药物来治疗小鼠。使用流式细胞术检测经处理的人类巨噬细胞释放的活性氧 (ROS)。通过蛋白质印迹分析SIRT1和NF-κB的表达。通过共免疫沉淀检测 SIRT1 和 NF-κB 相互作用的 RelA/p65 亚基。我们发现 EM 抑制了 CSE 诱导的人巨噬细胞中释放的 ROS，这与小鼠巨噬细胞和肺中 SIRT1 蛋白表达的增加相吻合，导致 NF-κB 乙酰化受到抑制，表达与炎症介质的减少相关。结论：这些发现表明 EM 增加 SIRT1，导致 NF-κB 的乙酰化/表达，从而减少香烟烟​​雾驱动的 NF-κB 依赖性促炎细胞因子。我们发现 EM 抑制了 CSE 诱导的人巨噬细胞中释放的 ROS，这与小鼠巨噬细胞和肺中 SIRT1 蛋白表达的增加相吻合，导致 NF-κB 乙酰化受到抑制，表达与炎症介质的减少相关。结论：这些发现表明 EM 增加 SIRT1，导致 NF-κB 的乙酰化/表达，从而减少香烟烟​​雾驱动的 NF-κB 依赖性促炎细胞因子。我们发现 EM 抑制了 CSE 诱导的人巨噬细胞中释放的 ROS，这与小鼠巨噬细胞和肺中 SIRT1 蛋白表达的增加相吻合，导致 NF-κB 乙酰化受到抑制，表达与炎症介质的减少相关。结论：这些发现表明 EM 增加 SIRT1，导致 NF-κB 的乙酰化/表达，从而减少香烟烟​​雾驱动的 NF-κB 依赖性促炎细胞因子。