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首页> 外文期刊>Nanotoxicology >Nano-sized zinc oxide and silver, but not titanium dioxide, induce innate and adaptive immunity and antiviral response in differentiated THP-1 cells
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Nano-sized zinc oxide and silver, but not titanium dioxide, induce innate and adaptive immunity and antiviral response in differentiated THP-1 cells

机译：纳米大小的氧化锌和银，但不是二氧化钛，在分化的THP-1细胞中诱导先天和自适应免疫和抗病毒反应

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Nano-sized metal oxides are currently the most manufactured nanomaterials (NMs), and are increasingly used in consumer products. Recent exposure data reveal a genuine potential for adverse health outcomes for a vast array of NMs, however the underlying mechanisms are not fully understood. To elucidate size-related molecular effects, differentiated THP-1 cells were exposed to nano-sized materials (n-TiO2, n-ZnO and n-Ag), or their bulk-sized (b-ZnO and b-TiO2) or ionic (i-Ag) counterparts, and genome-wide gene expression changes were studied at low-toxic concentrations (<15% cytotoxicity). TiO2 materials were nontoxic in MTT assay, inducing only minor transcriptional changes. ZnO and Ag elicited dose-dependent cytotoxicity, wherein ionic and particulate effects were synergistic with respect to n-ZnO-induced cytotoxicity. In gene expression analyzes, 6h and 24h samples formed two separate hierarchical clusters. N-ZnO and n-Ag shared only 3.1% and 24.6% differentially expressed genes (DEGs) when compared to corresponding control. All particles, except TiO2, activated various metallothioneins. At 6h, n-Zn, b-Zn and n-Ag induced various immunity related genes associating to pattern recognition (including toll-like receptor), macrophage maturation, inflammatory response (TNF and IL-1beta), chemotaxis (CXCL8) and leucocyte migration (CXCL2-3 and CXCL14). After 24h exposure, especially n-Ag induced the expression of genes related to virus recognition and type I interferon responses. These results strongly suggest that in addition to ionic effects mediated by metallothioneins, n-Zn and n-Ag induce expression of genes involved in several innate and adaptive immunity associated pathways, which are known to play crucial role in immuno-regulation. This raises the concern of safe use of metal oxide and metal nanoparticle products, and their biological effects.
机译：纳米大小的金属氧化物是目前最具制造的纳米材料（NMS），越来越多地用于消费产品。最近的曝光数据显示了大量NMS的不利健康结果的真正潜力，但潜在的机制尚未完全理解。为了阐明尺寸相关的分子效应，将分化的THP-1细胞暴露于纳米大小的材料（N-TiO 2，N-ZnO和N-Ag），或其体积大小（B-ZnO和B-TiO 2）或离子（I-Ag）对应物，并在低毒浓度（<15％细胞毒性）中研究了基因组基因表达变化。 TiO2材料在MTT测定中存在无毒，仅诱导轻微的转录变化。 ZnO和Ag引发剂量依赖性细胞毒性，其中离子和颗粒作用相对于N- ZnO诱导的细胞毒性是协同的。在基因表达分析中，6H和24H样品形成了两个单独的分层簇。与相应的对照相比，N-ZnO和N-AG仅共用3.1％和24.6％差异表达基因（DEGS）。除TiO2之外的所有颗粒，激活了各种金属噻嗪。在6h，N-Zn，B-Zn和N-Ag诱导与模式识别（包括Toll样受体），巨噬细胞成熟，炎症反应（TNF和IL-1Beta），趋化性（CXCL8）和白细胞相关联的各种免疫相关基因。迁移（CXCL2-3和CXCL14）。 24h暴露后，特别是N-AG诱导与病毒识别和I型干扰素反应相关的基因的表达。这些结果强烈表明，除了由金属硫蛋白蛋白介导的离子效应外，N-Zn和N-Ag诱导参与几种先天和适应性免疫相关途径的基因的表达，这已知是在免疫调节中起到至关重要的作用。这提高了安全使用金属氧化物和金属纳米粒子产品的关注及其生物学作用。

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