Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes
Copyright © 2020 Kristine Midtbö et al..
Inflammasomes cleave and activate interleukin- (IL-) 1β and IL-18 which have both shared and unique biological functions. IL-1β is an important mediator of the acute phase response to infections and tissue damage, whereas IL-18 takes part in activation and tailoring of the adaptive immune response. While IL-1β has served as the prototypic indicator of inflammasome activation, few studies have compared the potential differences in IL-1β and IL-18 production during inflammasome activation. Since these cytokines partake in different immune pathways, the involvement of inflammasome activity in different conditions needs to be described beyond IL-1β production alone. To address a potential heterogeneity in inflammasome functionality, ATP, chitosan, or silica oxide (SiO2) were used to induce NLRP3 inflammasome activation in THP-1 cells and the subsequent outcomes were quantified. Despite using doses of the inflammasome inducers yielding similar release of IL-1β, SiO2-stimulated cells showed a lower concentration of released IL-18 compared to ATP and chitosan. Hence, the cells stimulated with SiO2 responded with a distinctly different IL-18 : IL-1β ratio. The difference in the IL-18 : IL-1β ratio for SiO2 was constant over different doses. While all downstream responses were strictly dependent on a functional NLRP3 inflammasome, the differences did not depend on the level of gene expression, caspase-1 activity, or pyroptosis. We suggest that the NLRP3 inflammasome response should be considered a dynamic process, which can be described by taking the ratio between IL-1β and IL-18 into account and moving away from an on/off perspective of inflammasome activation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2020 |
|---|---|
| Enthalten in: |
Mediators of inflammation - 2020(2020) vom: 01., Seite 4651090 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Midtbö, Kristine [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
8L70Q75FXE |
|---|
| Anmerkungen: |
Date Completed 06.10.2021 Date Revised 06.10.2021 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1155/2020/4651090 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM317130994 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM317130994 | ||
| 003 | DE-627 | ||
| 005 | 20231225162610.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1155/2020/4651090 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1057.xml |
| 035 | |a (DE-627)NLM317130994 | ||
| 035 | |a (NLM)33144845 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Midtbö, Kristine |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.10.2021 | ||
| 500 | |a Date Revised 06.10.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Kristine Midtbö et al. | ||
| 520 | |a Inflammasomes cleave and activate interleukin- (IL-) 1β and IL-18 which have both shared and unique biological functions. IL-1β is an important mediator of the acute phase response to infections and tissue damage, whereas IL-18 takes part in activation and tailoring of the adaptive immune response. While IL-1β has served as the prototypic indicator of inflammasome activation, few studies have compared the potential differences in IL-1β and IL-18 production during inflammasome activation. Since these cytokines partake in different immune pathways, the involvement of inflammasome activity in different conditions needs to be described beyond IL-1β production alone. To address a potential heterogeneity in inflammasome functionality, ATP, chitosan, or silica oxide (SiO2) were used to induce NLRP3 inflammasome activation in THP-1 cells and the subsequent outcomes were quantified. Despite using doses of the inflammasome inducers yielding similar release of IL-1β, SiO2-stimulated cells showed a lower concentration of released IL-18 compared to ATP and chitosan. Hence, the cells stimulated with SiO2 responded with a distinctly different IL-18 : IL-1β ratio. The difference in the IL-18 : IL-1β ratio for SiO2 was constant over different doses. While all downstream responses were strictly dependent on a functional NLRP3 inflammasome, the differences did not depend on the level of gene expression, caspase-1 activity, or pyroptosis. We suggest that the NLRP3 inflammasome response should be considered a dynamic process, which can be described by taking the ratio between IL-1β and IL-18 into account and moving away from an on/off perspective of inflammasome activation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a IL1B protein, human |2 NLM | |
| 650 | 7 | |a Interleukin-18 |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a NLRP3 protein, human |2 NLM | |
| 650 | 7 | |a Adenosine Triphosphate |2 NLM | |
| 650 | 7 | |a 8L70Q75FXE |2 NLM | |
| 700 | 1 | |a Eklund, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Särndahl, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Persson, Alexander |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Mediators of inflammation |d 1992 |g 2020(2020) vom: 01., Seite 4651090 |w (DE-627)NLM091636949 |x 1466-1861 |7 nnns |
| 773 | 1 | 8 | |g volume:2020 |g year:2020 |g day:01 |g pages:4651090 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1155/2020/4651090 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 2020 |j 2020 |b 01 |h 4651090 | ||