银纳米颗粒影响肺上皮细胞系的炎症反应

A. Fehaid, R. Fujii, Takeshi Sato, A. Taniguchi
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引用次数: 16

摘要

银纳米粒子(AgNPs)具有炎症和抗炎双重作用;然而,其抗炎作用的分子机制尚不清楚。在本研究中,我们研究了AgNPs对炎症反应的影响。我们使用肿瘤坏死因子-α (tnf -α)作为体外炎症模型,在肺上皮细胞系中诱导炎症反应。观察AgNPs对tnf α诱导的炎症反应的影响。促炎因子IL-1β和IL-18 mRNA表达上调。然而,AgNPs降低了tnf α诱导的IL-1β和IL-18的上调。AgNPs降低tnf α诱导的NF-KB应答、活性氧(ROS)生成、Nod样受体家族- pyrin结构域3 (NLRP3)基因表达和caspase-1激活,表明AgNPs的抗炎作用是通过抑制NF-KB转录和炎症小体途径实现的。相反,AgNPs单独诱导NF-KB转录和炎性体途径的激活,提示它们参与AgNPs炎症作用的分子机制。总之,这些发现表明,AgNPs单独的剂量依赖性炎症作用和AgNPs对tnf α诱导的炎症反应的抗炎作用的分子机制涉及两种不同的途径。了解这一机制将有助于提高AgNPs的医学应用,并提示其作为TNFα抑制剂治疗TNFα诱导的炎症性疾病的潜力。
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Silver Nanoparticles Affect the Inflammatory Response in a Lung Epithelial Cell Line
Silver nanoparticles (AgNPs) have a dual effect showing both inflammatory and anti-inflammatory effects; however, the molecular mechanism of their anti-inflammatory effect is not clearly understood. In this study, we investigated the effect of AgNPs on the inflammatory response. We induced an inflammatory response in a lung epithelial cell line using tumor necrosis factor-α (TNFα) as an in vitro inflammatory model. Then the effect of AgNPs on the TNFα-induced inflammatory response was observed. The mRNA expression of pro-inflammatory cytokines (IL-1β and IL-18) showed upregulation of IL-1β by AgNPs alone. However, AgNPs reduced the TNFα-induced upregulation of IL-1β and IL-18. AgNPs reduced the TNFα-induced NF-KB response, reactive oxygen species (ROS) generation, Nod Like Receptor Family-Pyrin domain containing 3 (NLRP3) gene expression, and caspase-1 activation, indicating that the anti-inflammatory effect of AgNPs was by inhibition of both NF-KB transcriptional and inflammasome pathways. Conversely, AgNPs alone induced the activation of both NF-KB transcriptional and inflammasome pathways, suggesting their involvement in the molecular mechanism of the inflammatory effect of AgNPs. Altogether, these findings show that two different pathways are involved in the molecular mechanism of both the dose-dependent inflammatory effect of AgNPs alone and the anti-inflammatory effect of AgNPs against the TNFα-induced inflammatory response. Understanding this mechanism will help to improve the medical applications of AgNPs and suggest their potential as a TNFα inhibitor to treat TNFα-induced inflammatory diseases.
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