Human Scavenger Receptor A1-Mediated Inflammatory Response to Silica Particle Exposure Is Size Specific.
Human Scavenger Receptor A1-Mediated Inflammatory Response to Silica Particle Exposure Is Size Specific.
复制标题
DOI：
10.3389/fimmu.2017.00379
复制
发表时间：
2017
影响因子：
7.3
通讯作者：
Tsutsumi Y
中科院分区：
文献类型：
--
作者：
Nishijima N;Hirai T;Misato K;Aoyama M;Kuroda E;Ishii KJ;Higashisaka K;Yoshioka Y;Tsutsumi Y
纳米技术在医疗保健领域的应用有许多潜在的好处;然而，我们对纳米颗粒与免疫系统之间相互作用的理解仍然不完整。尽管纳米颗粒的许多生物效应与粒径呈负相关，但有些明显具有尺寸特异性，并且这些尺寸特异性生物效应的机制仍然未知。在这里，我们检查了二氧化硅颗粒在THP-1细胞中的促炎作用与颗粒尺寸有关;使用了大的总体尺寸范围，颗粒直径之间的间隔很窄（颗粒直径：10、30、50、70、100、300和1，000 nm）。暴露于二氧化硅颗粒诱导的促炎细胞因子白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的分泌呈钟形分布，其中直径为50 nm的二氧化硅纳米颗粒诱导的分泌最大，直径较小或较大的颗粒的影响逐渐减弱。我们发现，阻断IL-1β分泌可显著抑制TNF-α分泌，表明IL-1β在暴露于二氧化硅颗粒诱导的炎症级联反应中位于TNF-α的上游，并且IL-1β分泌的诱导依赖于NLRP 3炎性小体和二氧化硅颗粒通过内吞作用进入细胞的摄取。然而，二氧化硅颗粒摄取的定量分析表明，IL-1β分泌与细胞摄取的二氧化硅颗粒量无关。进一步的研究表明，直径为50或100 nm但不是10或1,000 nm的二氧化硅纳米颗粒对IL-1β分泌和摄取的诱导依赖于清道夫受体（SR）A1。此外，在检查的二氧化硅颗粒中，只有直径为50 nm的二氧化硅颗粒通过激活Mer受体酪氨酸激酶（SR A1的信号介体）诱导强烈的IL-1β分泌。总之，我们的研究结果表明，SR A1介导的促炎反应是依赖于配体的大小和SR A1介导的内吞作用和受体介导的信号传导需要产生最大的促炎反应暴露于二氧化硅颗粒。
The application of nanotechnology in the health care setting has many potential benefits; however, our understanding of the interactions between nanoparticles and our immune system remains incomplete. Although many of the biological effects of nanoparticles are negatively correlated with particle size, some are clearly size specific and the mechanisms underlying these size-specific biological effects remain unknown. Here, we examined the pro-inflammatory effects of silica particles in THP-1 cells with respect to particle size; a large overall size range with narrow intervals between particle diameters (particle diameter: 10, 30, 50, 70, 100, 300, and 1,000 nm) was used. Secretion of the pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced by exposure to the silica particles had a bell-shaped distribution, where the maximal secretion was induced by silica nanoparticles with a diameter of 50 nm and particles with smaller or larger diameters had progressively less effect. We found that blockade of IL-1β secretion markedly inhibited TNF-α secretion, suggesting that IL-1β is upstream of TNF-α in the inflammatory cascade induced by exposure to silica particles, and that the induction of IL-1β secretion was dependent on both the NLRP3 inflammasome and on uptake of the silica particles into the cells via endocytosis. However, a quantitative analysis of silica particle uptake showed that IL-1β secretion was not correlated with the amount of silica particles taken up by the cells. Further investigation revealed that the induction of IL-1β secretion and uptake of silica nanoparticles with diameters of 50 or 100 nm, but not of 10 or 1,000 nm, was dependent on scavenger receptor (SR) A1. In addition, of the silica particles examined, only those with a diameter of 50 nm induced strong IL-1β secretion via activation of Mer receptor tyrosine kinase, a signal mediator of SR A1. Together, our results suggest that the SR A1-mediated pro-inflammatory response is dependent on ligand size and that both SR A1-mediated endocytosis and receptor-mediated signaling are required to produce the maximal pro-inflammatory response to exposure to silica particles.