Biomaterial Database

Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods. 2022

Rob J Vandebriel, and Sylvie Remy, and Jolanda P Vermeulen, and Evelien G E Hurkmans, and Kirsten Kevenaar, and Neus G Bastús, and Beatriz Pelaz, and Mahmoud G Soliman, and Victor F Puntes, and Wolfgang J Parak, and Jeroen L A Pennings, and Inge Nelissen

Centre for Health Protection, National Institute for Public Health & the Environment, 3720 BA Bilthoven, The Netherlands.

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.

UI	MeSH Term	Description	Entries
D006046	Gold	A yellow metallic element with the atomic symbol Au, atomic number 79, and atomic weight 197. It is used in jewelry, goldplating of other metals, as currency, and in dental restoration. Many of its clinical applications, such as ANTIRHEUMATIC AGENTS, are in the form of its salts.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071199	NLR Family, Pyrin Domain-Containing 3 Protein	An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME.	Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D043942	Nanotubes	Nanometer-sized tubes composed of various substances including carbon (CARBON NANOTUBES), boron nitride, or nickel vanadate.	Nanorods,Nanorod,Nanotube
D053768	Metal Nanoparticles	Nanoparticles produced from metals whose uses include biosensors, optics, and catalysts. In biomedical applications the particles frequently involve the noble metals, especially gold and silver.	Metal Nanocrystals,Metallic Nanocrystals,Metallic Nanoparticles,Metal Nanocrystal,Metal Nanoparticle,Metallic Nanocrystal,Metallic Nanoparticle,Nanocrystal, Metal,Nanocrystal, Metallic,Nanocrystals, Metal,Nanocrystals, Metallic,Nanoparticle, Metal,Nanoparticle, Metallic,Nanoparticles, Metal,Nanoparticles, Metallic
D058847	Inflammasomes	Multiprotein complexes that mediate the activation of CASPASE-1. Dysregulation of inflammasomes has also been linked to a number of autoinflammatory and autoimmune disorders.	Inflammasome,Pyroptosome,Pyroptosomes