Signalling-Dependent Adverse Health Effects of Carbon Nanoparticles Are Prevented by the Compatible Solute Mannosylglycerate (Firoin) In Vitro and In Vivo
Signalling-Dependent Adverse Health Effects of Carbon Nanoparticles Are Prevented by the Compatible Solute Mannosylglycerate (Firoin) In Vitro and In Vivo
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DOI：
10.1371/journal.pone.0111485
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发表时间：
2014-11-21
期刊：
影响因子：
3.7
通讯作者：
Unfried, Klaus
中科院分区：
文献类型：
--
作者：
Autengruber, Andrea;Sydlik, Ulrich;Unfried, Klaus
吸入燃烧产生的纳米颗粒会对呼吸道产生不良健康影响。在这种情况下，膜偶联信号传导的诱导被认为是组织稳态和促炎反应变化的原因。这些分子细胞反应的鉴定允许寻求干扰这些不良反应的策略。在当前的研究中，我们研究了来自嗜热细菌的结构不同的相容性溶质甘露糖基甘油酸酯（firoin）和来自嗜盐细菌的四氢嘧啶，以减少由肺中靶细胞中的碳纳米颗粒触发的信号通路的能力。用这两种物质预处理肺上皮细胞可降低丝裂原活化蛋白激酶的颗粒特异性活化，并降低增殖和凋亡终点。Firoin应用到动物的肺中，如四氢嘧啶，导致颗粒暴露诱导的嗜肺性肺部炎症显著减少。通过减少抗凋亡膜依赖性信号传导，两种物质均显著降低了碳纳米颗粒对离体人中性粒细胞的促炎作用。本研究的数据以及早期的研究表明，两种结构上不相关的相容性溶质能够通过干扰信号传导事件来防止气道对碳纳米颗粒的致病反应。研究结果强调了相容性溶质对气道颗粒暴露引起的不良健康影响的预防或治疗潜力。
The inhalation of combustion-derived nanoparticles leads to adverse health effects in the airways. In this context the induction of membrane-coupled signalling is considered as causative for changes in tissue homeostasis and pro-inflammatory reactions. The identification of these molecular cell reactions allowed to seek for strategies which interfere with these adverse effects. In the current study, we investigated the structurally different compatible solutes mannosylglycerate (firoin) from thermophilic bacteria and ectoine from halophilic bacteria for their capability to reduce signalling pathways triggered by carbon nanoparticles in target cells in the lung. The pre-treatment of lung epithelial cells with both substances decreased the particle-specific activation of mitogen-activated protein kinases and also the endpoints proliferation and apoptosis. Firoin applied into the lungs of animals, like ectoine, led to a significant reduction of the neutrophilic lung inflammation induced by particle exposure. The pro-inflammatory effect of carbon nanoparticles on human neutrophil granulocytes ex vivo was significantly reduced by both substances via the reduction of the anti-apoptotic membrane-dependent signalling. The data of this study together with earlier studies demonstrate that two structurally non-related compatible solutes are able to prevent pathogenic reactions of the airways to carbon nanoparticles by interfering with signalling events. The findings highlight the preventive or therapeutic potential of compatible solutes for adverse health effects caused by particle exposure of the airways.