Sistema de Salut de Catalunya
Institut Català de la Salut
[Vandebriel RJ, Vermeulen JP, Hurkmans EGE, Kevenaar K] Centre for Health Protection, National Institute for Public Health & the Environment, Bilthoven, The Netherlands. [Remy S] Health Unit, VITO NV, Mol, Belgium. [Bastús NG] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona, Bellaterra, Spain. [Puntes VF] Institut Català de Nanociència i Nanotecnologia (ICN2), Consejo Superior de Investigaciones Científicas (CSIC), The Barcelona Institute of Science and Technology (BIST), Universitat Autònoma de Barcelona, Bellaterra, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2022-09-09T07:35:02Z
2022-09-09T07:35:02Z
2022-05-20
Gold; Inflammation; Nanorod
Oro; Inflamación; Nanorod
Or; Inflamació; Nanorod
The widespread and increasing use of engineered nanomaterials (ENM) increases the risk of human exposure, generating concern that ENM may provoke adverse health effects. In this respect, their physicochemical characteristics are critical. The immune system may respond to ENM through inflammatory reactions. The NLRP3 inflammasome responds to a wide range of ENM, and its activation is associated with various inflammatory diseases. Recently, anisotropic ENM have become of increasing interest, but knowledge of their effects on the immune system is still limited. The objective of the study was to compare the effects of gold ENM of different shapes on NLRP3 inflammasome activation and related signalling pathways. Differentiated THP-1 cells (wildtype, ASC- or NLRP3-deficient), were exposed to PEGylated gold nanorods, nanostars, and nanospheres, and, thus, also different surface chemistries, to assess NLRP3 inflammasome activation. Next, the exposed cells were subjected to gene expression analysis. Nanorods, but not nanostars or nanospheres, showed NLRP3 inflammasome activation. ASC- or NLRP3-deficient cells did not show this effect. Gene Set Enrichment Analysis revealed that gold nanorod-induced NLRP3 inflammasome activation was accompanied by downregulated sterol/cholesterol biosynthesis, oxidative phosphorylation, and purinergic receptor signalling. At the level of individual genes, downregulation of Paraoxonase-2, a protein that controls oxidative stress, was most notable. In conclusion, the shape and surface chemistry of gold nanoparticles determine NLRP3 inflammasome activation. Future studies should include particle uptake and intracellular localization.
This research was funded by the EU FP7 project FutureNanoNeeds (GA N° 604602), RIVM, and VITO.
Article
Published version
English
Nanopartícules; Nanotubs; Or; TECHNOLOGY, INDUSTRY, AND AGRICULTURE::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanotubes; CHEMICALS AND DRUGS::Macromolecular Substances::Multiprotein Complexes::Inflammasomes; TECHNOLOGY, INDUSTRY, AND AGRICULTURE::Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles::Metal Nanoparticles; TECNOLOGÍA, INDUSTRIA Y AGRICULTURA::tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanotubos; COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::complejos multiproteicos::inflamasomas; TECNOLOGÍA, INDUSTRIA Y AGRICULTURA::tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas::nanopartículas metálicas
MDPI
International Journal of Molecular Sciences;23(10)
https://doi.org/10.3390/ijms23105763
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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