title: Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation.
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.
authors.affiliation: UMR MD3, EA2405 Polarisation des Macrophages et Récepteurs Nucléaires dans les Pathologies Inflammatoires et Infectieuses, Université Paul Sabatier, Toulouse, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Meunier
authors.forename: Agnès
authors.initials: A
authors.lastname: Coste
authors.forename: David
authors.initials: D
authors.lastname: Olagnier
authors.forename: Hélène
authors.initials: H
authors.lastname: Authier
authors.forename: Lise
authors.initials: L
authors.lastname: Lefèvre
authors.forename: Christophe
authors.initials: C
authors.lastname: Dardenne
authors.forename: José
authors.initials: J
authors.lastname: Bernad
authors.forename: Maryse
authors.initials: M
authors.lastname: Béraud
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Flahaut
authors.forename: Bernard
authors.initials: B
authors.lastname: Pipy
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D008422:Materials Testing; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D037742:Nanotubes, Carbon
chemical_list: D058847:Inflammasomes; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D037742:Nanotubes, Carbon