Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2019 Aug 5;14:1741-1752. doi: 10.2147/COPD.S202904. eCollection 2019.
Particulate matter (PM) has been implicated as a risk factor for airway injury. However, the molecular mechanisms remain largely unclear. The goal of this study was to determine whether sirtuin1 (SIRT1), an anti-inflammatory and antiaging protein, protects against PM-induced airway inflammation.
The effect of SIRT1 on PM-induced airway inflammation was assessed by using in vivo models of airway inflammation induced by PM and in vitro culture of human bronchial epithelial (HBE) cells exposed to PM, resveratrol (SIRT1 activator), or both.
PM-stimulated HBE cells showed a significant decrease in SIRT1 but a notable increase in inflammatory cytokines. gene silencing further enhanced PM-induced expression of inflammatory cytokines. In contrast, resveratrol, a SIRT1 activator, reduced the expression of these cytokines compared with the control cells. In vivo, SIRT1 expression was significantly decreased in lung tissues of PM-exposed mice. Interestingly, resveratrol treatment reversed the enhanced total cells, neutrophils and inflammatory cytokines in PM-induced mice. Moreover, SIRT1 mediated PM-induced inflammatory cytokines expression at least partly through MAPK pathways.
These findings suggest that SIRT1 is involved in the pathogenesis of PM-induced airway inflammation and activation of SIRT1 could prevent airway disorders or disease exacerbations induced by airborne particulate pollution.
颗粒物（PM）已被认为是气道损伤的一个风险因素。然而，其分子机制在很大程度上仍不清楚。本研究的目的是确定是否沉默信息调节因子 1（SIRT1），一种具有抗炎和抗衰老作用的蛋白质，可以防止 PM 引起的气道炎症。
通过 PM 诱导的气道炎症的体内模型和暴露于 PM、白藜芦醇（SIRT1 激活剂）或两者的人支气管上皮（HBE）细胞的体外培养，评估 SIRT1 对 PM 诱导的气道炎症的影响。
PM 刺激的 HBE 细胞显示 SIRT1 显著减少，但炎症细胞因子明显增加。基因沉默进一步增强了 PM 诱导的炎症细胞因子的表达。相比之下，SIRT1 激活剂白藜芦醇与对照细胞相比降低了这些细胞因子的表达。在体内，暴露于 PM 的小鼠肺组织中的 SIRT1 表达明显降低。有趣的是，白藜芦醇治疗逆转了 PM 诱导的小鼠中总细胞、嗜中性粒细胞和炎症细胞因子的增强。此外，SIRT1 通过 MAPK 通路介导 PM 诱导的炎症细胞因子表达。
这些发现表明 SIRT1 参与 PM 诱导的气道炎症的发病机制，激活 SIRT1 可以防止空气传播的颗粒物污染引起的气道疾病或疾病恶化。
