کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
877587 | 911035 | 2012 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation](/preview/png/877587.png)
Because of their outstanding physical properties, carbon nanotubes (CNTs) are promising new materials in the field of nanotechnology. It is therefore imperative to assess their adverse effects on human health. Monocytes/macrophages that recognize and eliminate the inert particles constitute the main target of CNTs. In this article, we report our finding that double-walled CNTs (DWCNTs) synergize with Toll-like receptor agonists to enhance IL-1β release in human monocytes. We show that DWCNTs–induced IL-1β secretion is exclusively linked to caspase-1 and to Nlrp3 inflammasome activation in human monocytes. We also establish that this activation requires DWCNTs phagocytosis and potassium efflux, but not reactive oxygen specied (ROS) generation. Moreover, inhibition of lysosomal acidification or cathepsin-B activation reduces DWCNT-induced IL-1β secretion, suggesting that Nlrp3 inflammasome activation occurs via lysosomal destabilization. Thus, DWCNTs present a health hazard due to their capacity to activate Nlrp3 inflammasome, recalling the inflammation caused by asbestos and hence demonstrating that they should be used with caution.From the Clinical EditorThis is a very important biosafety/toxicity study regarding double walled carbon nanotubes. The investigators demonstrate that such nanotubes do represent a health hazard due to their capacity to activate Nlrp3 inflammasome, resembling the inflammation caused by asbestos. While further study of this phenomenon is definitely needed, the above findings clearly suggest that special precautions need to be taken when applying these nanoparticles in human disease research.
Graphical AbstractScheme explaining the mechanism leading to the activation of the Nlrp3 inflammasome by DWCNTs. IL-1β secretion in response to DWCNT treatment requires a first signal dependent on TLRs. This TLR-dependent signal leads to pro-IL1β synthesis. Then, the DWCNTs are phagocytosed by monocytes, causing phagosomal acidification and cathepsin B activation and finally leading to Nlrp3 inflammasome activation. This activation also requires a potassium efflux, but not ROS generation.Figure optionsDownload high-quality image (105 K)Download as PowerPoint slide
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 8, Issue 6, August 2012, Pages 987–995