Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation

Our plain-English summary of Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation, by E. Meunier, A. Coste, D. Olagnier, et al (Nanomedicine, 2012).

The study

• Authors: E. Meunier, A. Coste, D. Olagnier, H. Authier, L. Lefèvre, C. Dardenne, J. Bernad, M. Béraud, E. Flahaut, B. Pipy
• Journal: Nanomedicine
• Published: 2012;8(6):987-95
• Cited by: 87 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

In plain English

In this laboratory study, the authors exposed monocytes (a type of white blood cell) from the blood of healthy donors in Toulouse, France, to double-walled carbon nanotubes. The sample was about 80% double-walled tubes, with 15% single-walled tubes and 5% of a type the article labels TWCNTs. Asbestos was not tested. In cells first primed with a bacterial substance (LPS), the nanotubes caused a strong increase in release of the inflammatory proteins IL-1β and IL-18, but not TNFα or IL-6. The nanotubes did not induce IL-1β or IL-18 release in unprimed cells, and carbon black did not induce it either. IL-1β release fell when the authors blocked the enzyme caspase-1, the Nlrp3 gene, potassium loss from cells, particle uptake, lysosome acidification, or cathepsin-B. The nanotubes did not trigger reactive oxygen production. Cytokine levels were shown in figures, without numbers in the text. The authors concluded that the nanotubes present a health hazard because they activate the Nlrp3 inflammasome, recalling the inflammation caused by asbestos (a comparison based on other researchers' studies), and that they should be used with caution.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on human cells
• Who was studied: Primary human monocytes from healthy blood donors, obtained through the Etablissement Français du Sang, Toulouse, France. The number of donors is not stated. Some cells were also differentiated into macrophages.
• Exposure: Double-walled carbon nanotubes (DWCNTs), raw and oxidized. The sample was about 80% DWCNTs, 15% single-walled CNTs and 5% TWCNTs. They were compared with carbon black and ATP in cells primed with LPS or other Toll-like receptor agonists. No asbestos was tested.
• Main results:
  • DWCNTs did not induce IL-1β or IL-18 secretion in unprimed monocytes. In LPS-primed monocytes they produced a strong increase in IL-1β and IL-18 release.
  • Carbon black did not induce IL-1β or IL-18 secretion.
  • In LPS-primed monocytes, DWCNTs did not increase TNFα or IL-6 secretion compared with LPS alone.
  • IL-1β mRNA levels did not differ between LPS alone and LPS plus DWCNTs.
  • The caspase-1 inhibitor significantly decreased DWCNT-induced IL-1β secretion. The caspase-3 inhibitor did not.
  • Silencing Nlrp3 decreased IL-1β secretion in DWCNT-treated monocytes.
  • Preventing potassium efflux abolished DWCNT-induced IL-1β secretion.
  • Blocking actin-mediated phagocytosis (particle uptake) with Latrunculin A suppressed DWCNT-induced IL-1β secretion.
  • DWCNTs did not induce reactive oxygen species (ROS) production in the monocytes.
  • A non-specific cathepsin inhibitor significantly reduced DWCNT-induced IL-1β secretion. A specific inhibitor pointed to cathepsin-B as the main protease involved.
  • Bafilomycin A1, which blocks lysosomal acidification, significantly reduced the DWCNT-induced IL-1β response.
  • Oxidizing the DWCNT surface with nitric acid did not affect their ability to induce IL-1β release.
• The authors' conclusion: The authors concluded that DWCNTs present a health hazard because they activate the Nlrp3 inflammasome, recalling the inflammation caused by asbestos, and that they should be used with caution. The asbestos comparison rests on earlier studies by others cited in the article, not on asbestos tested here.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Phagocytosis, Inflammation.

Related studies

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• Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism — J. Palomäki, E. Välimäki, et al. (2011)
• Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β — A.S. Yazdi, G. Guarda, et al. (2010)
• High-temperature calcined fullerene nanowhiskers as well as long needle-like multi-wall carbon nanotubes have abilities to induce NLRP3-mediated IL-1β secretion — H. Cui, W. Wu, et al. (2014)
• Asbestos stimulation triggers differential cytokine release from human monocytes and alveolar macrophages — L.J. Geist, L.S. Powers, et al. (2000)
• Multi-walled carbon nanotubes induce stronger migration of inflammatory cells in vitro than asbestos or granular particles but a similar pattern of inflammatory mediators — G.A. Westphal, N. Rosenkranz, et al. (2019)

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