Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells

Introduction: Innate host defence against pathogen required NLRP3 inflammasome activation. Two steps of inflammasome complex activation are identified: Signal 1 or priming (expression of NLRP3 protein, pro-IL-1β, pro-IL-18 and pro-caspase-1), followed by Signal 2 or activation (expression of active...

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Main Authors: Abas, Razif, Wozniak, Marcin, Herbert, Karl
Format: Article
Published: Universiti Putra Malaysia 2019
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author Abas, Razif
Wozniak, Marcin
Herbert, Karl
author_facet Abas, Razif
Wozniak, Marcin
Herbert, Karl
author_sort Abas, Razif
collection UPM
description Introduction: Innate host defence against pathogen required NLRP3 inflammasome activation. Two steps of inflammasome complex activation are identified: Signal 1 or priming (expression of NLRP3 protein, pro-IL-1β, pro-IL-18 and pro-caspase-1), followed by Signal 2 or activation (expression of active IL-1β and IL-18). The purpose of this study was to investigate the possible mitochondrial role of superoxide generators and slow-release hydrogen sulfide generation in activating the NLRP3 inflammasome in THP-1 and endothelial cells (HUVEC and EA.hy926 cells). Methods: THP-1 cells were differentiated with PMA (5 ng/ml) up to 3 days. Later, LPS treatment (5 µg/ml) was administered for 24 h for Signal 1 priming followed by bzATP (300 µM) for 1 hour for Signal 2. Subsequently, the effects of intracellular generation of superoxide (mitoparaquat and paraquat at 1 and 5 µM) and hydrogen sulfide (GYY4137 and AP39) were investigated in differentiated THP-1 cells before and after LPS. Results: NLRP3 inflammasome activation were up-regulated in differentiated THP-1 cells. However, only EA.hy926 showed Signal 2 activation. The higher concentration of mitoparaquat (5 µM) was able to increase Signal 2. Interestingly, both slow-release hydrogen sulfide donors were able to reduce Signal 2 NLRP3 inflammasome. However, no active caspase-1 expression was observed. Conclusion: The effects of pro- and anti- inflammatory properties were observed by modulating IL-1β and IL-18 synthesis in differentiated THP-1 cells via redox active oxygen and sulfur species. Hence, promoting anti-atherosclerotic properties.
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spelling upm.eprints-990402023-01-31T03:38:23Z http://psasir.upm.edu.my/id/eprint/99040/ Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells Abas, Razif Wozniak, Marcin Herbert, Karl Introduction: Innate host defence against pathogen required NLRP3 inflammasome activation. Two steps of inflammasome complex activation are identified: Signal 1 or priming (expression of NLRP3 protein, pro-IL-1β, pro-IL-18 and pro-caspase-1), followed by Signal 2 or activation (expression of active IL-1β and IL-18). The purpose of this study was to investigate the possible mitochondrial role of superoxide generators and slow-release hydrogen sulfide generation in activating the NLRP3 inflammasome in THP-1 and endothelial cells (HUVEC and EA.hy926 cells). Methods: THP-1 cells were differentiated with PMA (5 ng/ml) up to 3 days. Later, LPS treatment (5 µg/ml) was administered for 24 h for Signal 1 priming followed by bzATP (300 µM) for 1 hour for Signal 2. Subsequently, the effects of intracellular generation of superoxide (mitoparaquat and paraquat at 1 and 5 µM) and hydrogen sulfide (GYY4137 and AP39) were investigated in differentiated THP-1 cells before and after LPS. Results: NLRP3 inflammasome activation were up-regulated in differentiated THP-1 cells. However, only EA.hy926 showed Signal 2 activation. The higher concentration of mitoparaquat (5 µM) was able to increase Signal 2. Interestingly, both slow-release hydrogen sulfide donors were able to reduce Signal 2 NLRP3 inflammasome. However, no active caspase-1 expression was observed. Conclusion: The effects of pro- and anti- inflammatory properties were observed by modulating IL-1β and IL-18 synthesis in differentiated THP-1 cells via redox active oxygen and sulfur species. Hence, promoting anti-atherosclerotic properties. Universiti Putra Malaysia 2019 Article PeerReviewed Abas, Razif and Wozniak, Marcin and Herbert, Karl (2019) Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells. Malaysian Journal of Medicine and Health Sciences, 15 (suppl.7). p. 4. ISSN 2636-9346 https://medic.upm.edu.my/jurnal_kami/volume_15_2019/mjmhs_vol_15_supplement_7_november_2019-53935
spellingShingle Abas, Razif
Wozniak, Marcin
Herbert, Karl
Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells
title Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells
title_full Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells
title_fullStr Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells
title_full_unstemmed Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells
title_short Mitochondrial redox modulation of NLRP3 inflammasome in differentiated THP-1 cells
title_sort mitochondrial redox modulation of nlrp3 inflammasome in differentiated thp 1 cells
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AT wozniakmarcin mitochondrialredoxmodulationofnlrp3inflammasomeindifferentiatedthp1cells
AT herbertkarl mitochondrialredoxmodulationofnlrp3inflammasomeindifferentiatedthp1cells