Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-induced Inflammation in Chronic Obstructive Pulmonary Disease
Klotho Reduction in Alveolar Macrophages Contributes to Cigarette Smoke Extract-induced Inflammation in Chronic Obstructive Pulmonary Disease
复制标题
肺泡巨噬细胞中 Klotho 的减少导致慢性阻塞性肺疾病中香烟烟雾提取物诱导的炎症。
DOI：
10.1074/jbc.m115.655431
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发表时间：
2015-11-13
影响因子：
4.8
通讯作者：
Yao, Xin
中科院分区：
文献类型：
--
作者：
Li, Lingling;Wang, Yujie;Yao, Xin
慢性阻塞性肺疾病（COPD）患者会出现异常炎症和肺功能加速下降。Klotho是一种抗衰老蛋白质，具有抗炎功能。然而，Klotho在COPD中的作用从未被研究过。本研究的目的是探讨肺泡巨噬细胞Klotho在COPD气道炎症中的可能作用。在非吸烟者、吸烟者和COPD患者的肺样本和外周血单核细胞中评估Klotho水平。体外研究香烟烟雾提取物（CSE）对Klotho表达的调控，并利用小干扰RNA（siRNA）和重组Klotho研究Klotho在CSE诱导的炎症中的作用。COPD患者肺内肺泡巨噬细胞和外周血单核细胞中Klotho表达减少。CSE降低Klotho表达和从MH-S细胞释放。内源性Klotho的敲除增强了MH-S细胞表达炎症介质，如MMP-9、IL-6和TNF-α。外源性Klotho抑制CSE诱导的炎症介质的表达。此外，我们发现Klotho与NF-κ B通路的I κ B α相互作用。地塞米松处理增加了MH-S细胞中Klotho的表达和释放水平。我们的研究结果表明，Klotho在肺部持续炎症中发挥作用，这反过来可能对COPD有治疗意义。
Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Klotho, an anti-aging protein, has an anti-inflammatory function. However, the role of Klotho has never been investigated in COPD. The aim of this study is to investigate the possible role of Klotho by alveolar macrophages in airway inflammation in COPD. Klotho levels were assessed in the lung samples and peripheral blood mononuclear cells of non-smokers, smokers, and patients with COPD. The regulation of Klotho expression by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and recombinant Klotho were employed to investigate the role of Klotho on CSE-induced inflammation. Klotho expression was reduced in alveolar macrophages in the lungs and peripheral blood mononuclear cells of COPD patients. CSE decreased Klotho expression and release from MH-S cells. Knockdown of endogenous Klotho augmented the expression of the inflammatory mediators, such as MMP-9, IL-6, and TNF-alpha, by MH-S cells. Exogenous Klotho inhibited the expression of CSE-induced inflammatory mediators. Furthermore, we showed that Klotho interacts with I kappa B alpha of the NF-kappa B pathway. Dexamethasone treatment increased the expression and release level of Klotho in MH-S cells. Our findings suggest that Klotho plays a role in sustained inflammation of the lungs, which in turn may have therapeutic implications in COPD.