Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods
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 rea...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/10/5763 |
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| author | Rob J. Vandebriel Sylvie Remy Jolanda P. Vermeulen Evelien G. E. Hurkmans Kirsten Kevenaar Neus G. Bastús Beatriz Pelaz Mahmoud G. Soliman Victor F. Puntes Wolfgang J. Parak Jeroen L. A. Pennings Inge Nelissen |
| author_facet | Rob J. Vandebriel Sylvie Remy Jolanda P. Vermeulen Evelien G. E. Hurkmans Kirsten Kevenaar Neus G. Bastús Beatriz Pelaz Mahmoud G. Soliman Victor F. Puntes Wolfgang J. Parak Jeroen L. A. Pennings Inge Nelissen |
| author_sort | Rob J. Vandebriel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:42:31Z |
| format | Article |
| id | doaj.art-735e9c0563464eab98cb6d485520a311 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:42:31Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-735e9c0563464eab98cb6d485520a3112023-11-23T11:28:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-05-012310576310.3390/ijms23105763Pathways Related to NLRP3 Inflammasome Activation Induced by Gold NanorodsRob J. Vandebriel0Sylvie Remy1Jolanda P. Vermeulen2Evelien G. E. Hurkmans3Kirsten Kevenaar4Neus G. Bastús5Beatriz Pelaz6Mahmoud G. Soliman7Victor F. Puntes8Wolfgang J. Parak9Jeroen L. A. Pennings10Inge Nelissen11Centre for Health Protection, National Institute for Public Health & the Environment, 3720 BA Bilthoven, The NetherlandsHealth Unit, VITO NV, 2400 Mol, BelgiumCentre for Health Protection, National Institute for Public Health & the Environment, 3720 BA Bilthoven, The NetherlandsCentre for Health Protection, National Institute for Public Health & the Environment, 3720 BA Bilthoven, The NetherlandsCentre for Health Protection, National Institute for Public Health & the Environment, 3720 BA Bilthoven, The NetherlandsInstitut 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, 08193 Barcelona, SpainCentro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Universidade de Santiago de Compostela, 15782 Santiago, SpainFachbereich Physik, CHyN, University of Hamburg, 22761 Hamburg, GermanyInstitut 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, 08193 Barcelona, SpainFachbereich Physik, CHyN, University of Hamburg, 22761 Hamburg, GermanyCentre for Health Protection, National Institute for Public Health & the Environment, 3720 BA Bilthoven, The NetherlandsHealth Unit, VITO NV, 2400 Mol, BelgiumThe 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.https://www.mdpi.com/1422-0067/23/10/5763inflammationNLRP3goldnanorodnanostarnanosphere |
| spellingShingle | Rob J. Vandebriel Sylvie Remy Jolanda P. Vermeulen Evelien G. E. Hurkmans Kirsten Kevenaar Neus G. Bastús Beatriz Pelaz Mahmoud G. Soliman Victor F. Puntes Wolfgang J. Parak Jeroen L. A. Pennings Inge Nelissen Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods International Journal of Molecular Sciences inflammation NLRP3 gold nanorod nanostar nanosphere |
| title | Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods |
| title_full | Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods |
| title_fullStr | Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods |
| title_full_unstemmed | Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods |
| title_short | Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods |
| title_sort | pathways related to nlrp3 inflammasome activation induced by gold nanorods |
| topic | inflammation NLRP3 gold nanorod nanostar nanosphere |
| url | https://www.mdpi.com/1422-0067/23/10/5763 |
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