Ti Ions Induce IL-1β Release by Activation of the NLRP3 Inflammasome in a Human Macrophage Cell Line
© 2022. The Author(s)..
The aim of the present study was to investigate whether titanium (Ti)-induced release of interleukin (IL)-1β acts through the assembly of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome. In addition, we examined whether particulate Ti or TiO2 activates the same intracellular pathways with the assembly of the NLRP3 inflammasome as Ti ions. Ti ions are known to induce IL-1β maturation and release by the formation of metal-protein aggregates. Wild-type THP-1 (wt.) cells and NLRP3- and ASC- (apoptosis-associated speck-like protein containing caspase recruitment domain (CARD)) knockdown cells were used in the experimental analyses. Macro- and nanoparticles (NPs) of both Ti and TiO2 were used as test agents. IL-1β release as a biomarker for inflammasome activation and cell viability was also analyzed. Periodate-oxidized adenosine triphosphate (oATP) was used to attenuate downstream signaling in NLRP3 inflammasome activation. Cellular uptake of Ti was examined using transmission electron microscopy. Cells exposed to the Ti-ion solution showed a dose-dependent increase in the release of IL-1β; conversely, exposure to particulate Ti did not result in increased IL-1β release. Cell viability was not affected by particulate Ti. Knockdown cells exposed to Ti showed a statistically significant reduction in the release of IL-1β compared with wt. cells (p < 0.001). Cellular uptake was detected in all Ti mixtures, and aggregates with various structures were observed. Ti ion-induced release of bioactive IL-1β in THP-1 cells involves the assembly of the NLRP3 inflammasome.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
Inflammation - 45(2022), 5 vom: 20. Okt., Seite 2027-2037 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pettersson, Mattias [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.09.2022 Date Revised 13.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10753-022-01672-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a The aim of the present study was to investigate whether titanium (Ti)-induced release of interleukin (IL)-1β acts through the assembly of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome. In addition, we examined whether particulate Ti or TiO2 activates the same intracellular pathways with the assembly of the NLRP3 inflammasome as Ti ions. Ti ions are known to induce IL-1β maturation and release by the formation of metal-protein aggregates. Wild-type THP-1 (wt.) cells and NLRP3- and ASC- (apoptosis-associated speck-like protein containing caspase recruitment domain (CARD)) knockdown cells were used in the experimental analyses. Macro- and nanoparticles (NPs) of both Ti and TiO2 were used as test agents. IL-1β release as a biomarker for inflammasome activation and cell viability was also analyzed. Periodate-oxidized adenosine triphosphate (oATP) was used to attenuate downstream signaling in NLRP3 inflammasome activation. Cellular uptake of Ti was examined using transmission electron microscopy. Cells exposed to the Ti-ion solution showed a dose-dependent increase in the release of IL-1β; conversely, exposure to particulate Ti did not result in increased IL-1β release. Cell viability was not affected by particulate Ti. Knockdown cells exposed to Ti showed a statistically significant reduction in the release of IL-1β compared with wt. cells (p < 0.001). Cellular uptake was detected in all Ti mixtures, and aggregates with various structures were observed. Ti ion-induced release of bioactive IL-1β in THP-1 cells involves the assembly of the NLRP3 inflammasome | ||
| 650 | 4 | |a Journal Article | |
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