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双层碳纳米管对固有免疫系统的生物学效应:对THP-1人单核细胞的体外研究

Biological effects of double-walled carbon nanotubes on the innate immune system: An in vitro study on THP-1 human monocytes.

作者信息

Dekali Samir, Bachelet Christine, Maunoir-Regimbal Séverine, Flahaut Emmanuel, Debouzy Jean-Claude, Crouzier David

机构信息

Institut de Recherche Biomédicale des Armées (IRBA), Département EBR/Unité des Risques Technologiques Emergents, 1, place du Général Valérie André, BP73, 91223 Brétigny-sur-Orge Cedex, France.

Institut de Recherche Biomédicale des Armées (IRBA), Département EBR/Unité des Risques Technologiques Emergents, 1, place du Général Valérie André, BP73, 91223 Brétigny-sur-Orge Cedex, France.

出版信息

Toxicology. 2016 Jul 15;365:1-8. doi: 10.1016/j.tox.2016.07.019. Epub 2016 Jul 27.

Abstract

DWCNTs have numerous industrial and biomedical applications and several studies reported that they could act as immunomodulator systems. The immune system is the first line of defence of the human body when exposed to particulate matter. In order to investigate DWCNTs' role on innate immunity, we used THP-1 monocytic cells for the purpose of this study. We showed that DWCNTs were not cytotoxic until 6h, 24h, 48h and 72h of incubation with THP-1 monocytic cells (concentrations tested from 10 to 50μg/mL). From 6h to 72h of incubation of THP-1 cells with DWCNTs, we measured a significant increase of the baseline cell index using xCELLigence(®) technology showing cell adhesion. After 24h of exposure, DWCNTs agglomerates were localized in THP-1 monocyte cytoplasm and cell adhesion was observed simultaneously with a significant increase in the expression of CD11b and CD14 cell surface proteins. Pro-inflammatory cytokine secretion (IL-1β, IL-6, IL-8, TNF-α and IL-10) was also measured in supernatants after 6h or 24h of exposure to DWCNTs. This pro-inflammatory response was increased in THP-1 monocytic cells pre-treated with LPS. Altogether, our data indicate that DWCNTs induce an increased pro-inflammatory response of THP-1 monocytes and seem to modulate cell surface protein expression confirming that DWCNTs could act as stimulators of innate immunity.

摘要

双壁碳纳米管(DWCNTs)有众多工业和生物医学应用,多项研究报道它们可作为免疫调节系统。免疫系统是人体接触颗粒物时的第一道防线。为了研究双壁碳纳米管对固有免疫的作用,本研究使用了THP - 1单核细胞。我们发现,在与THP - 1单核细胞孵育6小时、24小时、48小时和72小时(测试浓度为10至50μg/mL)时,双壁碳纳米管没有细胞毒性。在THP - 1细胞与双壁碳纳米管孵育6小时至72小时期间,我们使用xCELLigence(®)技术测量基线细胞指数显著增加,表明细胞发生黏附。暴露24小时后,双壁碳纳米管团聚物定位于THP - 1单核细胞胞质中,同时观察到细胞黏附,且细胞表面蛋白CD11b和CD14的表达显著增加。在暴露于双壁碳纳米管6小时或24小时后,还测量了上清液中促炎细胞因子的分泌(IL - 1β、IL - 6、IL - 8、TNF - α和IL - 10)。在用脂多糖(LPS)预处理的THP - 1单核细胞中,这种促炎反应增强。总之,我们的数据表明双壁碳纳米管可诱导THP - 1单核细胞的促炎反应增强,似乎还能调节细胞表面蛋白表达,证实双壁碳纳米管可作为固有免疫的刺激物。

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