Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods
Vandebriel, Rob J. (National Institute for Public Health & the Environment)
Remy, Sylvie (Health Unit)
Vermeulen, Jolanda P. (National Institute for Public Health & the Environment)
Hurkmans, Evelien G. E. (National Institute for Public Health & the Environment)
Kevenaar, Kirsten (National Institute for Public Health & the Environment)
Bastús, Neus G. (Institut Català de Nanociència i Nanotecnologia)
Pelaz, Beatriz (Universidade de Santiago de Compostela. Departamento de Química Inorgánica)
Soliman, Mahmoud G. (University of Hamburg)
Puntes, Víctor (Institut Català de Nanociència i Nanotecnologia)
Parak, Wolfgang J. (University of Hamburg)
Pennings, Jeroen L. A. (National Institute for Public Health & the Environment)
Nelissen, Inge (Health Unit)

Fecha:	2022
Resumen:	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.
Ayudas:	European Commission 604602
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Inflammation ; NLRP3 ; Gold ; Nanorod ; Nanostar ; Nanosphere ; Cholesterol ; Oxidative phosphorylation ; Purinergic receptor ; Paraoxonase-2
Publicado en:	International journal of molecular sciences, Vol. 23, Issue 10 (May 2022) , art. 5763, ISSN 1422-0067

DOI: 10.3390/ijms23105763
PMID: 35628574

22 p, 7.6 MB

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