Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes
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....
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/4651090 |
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| author | Kristine Midtbö Daniel Eklund Eva Särndahl Alexander Persson |
| author_facet | Kristine Midtbö Daniel Eklund Eva Särndahl Alexander Persson |
| author_sort | Kristine Midtbö |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a9fb78160dc84fe891ea507b6034847d |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a9fb78160dc84fe891ea507b6034847d2025-02-03T06:05:44ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/46510904651090Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human MonocytesKristine Midtbö0Daniel Eklund1Eva Särndahl2Alexander Persson3School of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedenSchool of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedenSchool of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedenSchool of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, SwedenInflammasomes 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.http://dx.doi.org/10.1155/2020/4651090 |
| spellingShingle | Kristine Midtbö Daniel Eklund Eva Särndahl Alexander Persson Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes Mediators of Inflammation |
| title | Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes |
| title_full | Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes |
| title_fullStr | Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes |
| title_full_unstemmed | Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes |
| title_short | Molecularly Distinct NLRP3 Inducers Mediate Diverse Ratios of Interleukin-1β and Interleukin-18 from Human Monocytes |
| title_sort | molecularly distinct nlrp3 inducers mediate diverse ratios of interleukin 1β and interleukin 18 from human monocytes |
| url | http://dx.doi.org/10.1155/2020/4651090 |
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