Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free. The human macrophage-differentiated THP.1 cell line was employed for cytotoxicity screening and based on the calculated IC50 values, the multi-walled carbon nanotubes (MWCNTs), ZnO, Ag and SiO2 NMs were found to be the most cytotoxic while single-walled carbon nanotubes (SWCNTs), TiO2, BaSO4 and CeO2 NMs, as well as the nanocellulose materials, were non-cytotoxic (at doses up to 100 µg/mL). Multiplex profiling of cytokine and chemokine secretion indicated that the TiO2, SiO2, BaSO4, CeO2 and nanocellulose materials induced potent inflammatory responses at sub-cytotoxic doses. Hierarchical clustering of cytokine responses coupled with pathway analysis demonstrated that the panel of ENMs could be segregated into two distinct groups characterized by activation and deactivation, respectively, of PPAR (peroxisome proliferator-activated receptor)/LXR (liver X receptor/retinoid X receptor) nuclear receptor pathways (NRPs). Furthermore, using rosiglitazone, a selective PPAR-γ agonist, we could show that PPAR-γ played an important role in the activation of inflammatory responses in cells exposed to TiO2 and SiO2 NMs. These studies show that ENMs of diverse chemical compositions can be grouped according to their inflammatory potential.

中文翻译：

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对十九种纳米材料的细胞毒性筛选和细胞因子分析可以根据致炎潜力对危害进行分级和分组。

工程纳米材料（ENM）的生产正用于越来越多的应用中。因此，重要的是根据潜在危害对ENM进行评估和分类。免疫系统是抵御异物的首要防御手段。在这里，我们对从联合研究中心（JRC）和商业渠道获得的19个代表性ENM进行了细胞因子谱分析。使用动态光散射进行理化表征。所有的ENM均显示无内毒素含量。将人类巨噬细胞分化的THP.1细胞系用于细胞毒性筛选，并根据计算的IC50值，发现多壁碳纳米管（MWCNT），ZnO，Ag和SiO2 NMs具有最大的细胞毒性，而单壁碳纳米管（SWCNT），TiO2，BaSO4和CeO2 NMs，以及纳米纤维素材料均无细胞毒性（最高剂量为100 µg / mL）。细胞因子和趋化因子分泌的多重分析表明，TiO2，SiO2，BaSO4，CeO2和纳米纤维素材料在亚细胞毒性剂量下诱导了强烈的炎症反应。细胞因子应答的分层聚类和途径分析表明，ENMs可分为两个不同的组，分别以PPAR（过氧化物酶体增殖物激活的受体）/ LXR（肝X受体/类维生素X受体）的激活和失活为特征核受体途径（NRP）。此外，使用罗格列酮（一种选择性的PPAR-γ激动剂），我们可以证明PPAR-γ在激活暴露于TiO2和SiO2 NMs的细胞中的炎症反应中起着重要作用。