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NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis

INTRODUCTION: Pattern recognition receptor-mediated signaling pathways have recently been elucidated to bridge the innate immune system and atherosclerosis. NLRP3 is a member of the NLR family. Upon activation, it initiates IL-1β and IL-18 processing, a key step in the inflammatory process of athero...

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Autores principales: Li, Wang Li, Hua, Li Gui, Qu, Peng, Yan, Wang Hong, Ming, Cui, Jun, Yuan Da, Yuan, Lou Da, Nan, Niu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016581/
https://www.ncbi.nlm.nih.gov/pubmed/27695484
http://dx.doi.org/10.5114/aoms.2016.61356
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author Li, Wang Li
Hua, Li Gui
Qu, Peng
Yan, Wang Hong
Ming, Cui
Jun, Yuan Da
Yuan, Lou Da
Nan, Niu
author_facet Li, Wang Li
Hua, Li Gui
Qu, Peng
Yan, Wang Hong
Ming, Cui
Jun, Yuan Da
Yuan, Lou Da
Nan, Niu
author_sort Li, Wang Li
collection PubMed
description INTRODUCTION: Pattern recognition receptor-mediated signaling pathways have recently been elucidated to bridge the innate immune system and atherosclerosis. NLRP3 is a member of the NLR family. Upon activation, it initiates IL-1β and IL-18 processing, a key step in the inflammatory process of atherosclerosis. MATERIAL AND METHODS: We used three different types of lipoproteins, ox-LDL, ox-HDL, and HDL, in Thp-1 at the concentration of 50 mg/l, 100 mg/l, and 150 mg/l respectively. Using real-time polymerase chain reaction and western blot, ELISA detected the expression of NLRP3 and downstream cytokines. NLRP3 siRNA was constructed to down-regulate expression of the NLRP3 gene via the RNA interference technique. 150 mg/l of ox-LDL, ox-HDL and HDL was added to the Thp-1 cell line respectively. We observed the changes in the expression of caspase-1, IL-1β and IL-18 when the NLRP3 gene was down-regulated. RESULTS: Ox-LDL and ox-HDL addition not only increases the expression of NLRP3, but also activates the NLRP3 downstream cytokines and caspase-1 and induces IL-1β and IL-18 secretion. Moreover, the effects of activation and induction are shown to have a dose-dependent manner. Expression of NLRP3 and its downstream inflammatory cytokines is reduced in the presence of HDL (p < 0.05). Furthermore, our data demonstrated that NLRP3 siRNA downregulates NLRP3 expression in mononuclear cells, thus leading to a dramatic reduction in the expression of caspase-1, IL-1β and IL-18 (p < 0.05). CONCLUSIONS: The data suggest that activation of the NLRP3 inflammasome is a critical step in caspase-1 activation and IL-1β and IL-18 secretion. Interference with the NLRP3 inflammasome can significantly inhibit the generation of cytokines, thus impeding the pathogenesis of inflammation.
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spelling pubmed-50165812016-10-01 NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis Li, Wang Li Hua, Li Gui Qu, Peng Yan, Wang Hong Ming, Cui Jun, Yuan Da Yuan, Lou Da Nan, Niu Arch Med Sci Basic Research INTRODUCTION: Pattern recognition receptor-mediated signaling pathways have recently been elucidated to bridge the innate immune system and atherosclerosis. NLRP3 is a member of the NLR family. Upon activation, it initiates IL-1β and IL-18 processing, a key step in the inflammatory process of atherosclerosis. MATERIAL AND METHODS: We used three different types of lipoproteins, ox-LDL, ox-HDL, and HDL, in Thp-1 at the concentration of 50 mg/l, 100 mg/l, and 150 mg/l respectively. Using real-time polymerase chain reaction and western blot, ELISA detected the expression of NLRP3 and downstream cytokines. NLRP3 siRNA was constructed to down-regulate expression of the NLRP3 gene via the RNA interference technique. 150 mg/l of ox-LDL, ox-HDL and HDL was added to the Thp-1 cell line respectively. We observed the changes in the expression of caspase-1, IL-1β and IL-18 when the NLRP3 gene was down-regulated. RESULTS: Ox-LDL and ox-HDL addition not only increases the expression of NLRP3, but also activates the NLRP3 downstream cytokines and caspase-1 and induces IL-1β and IL-18 secretion. Moreover, the effects of activation and induction are shown to have a dose-dependent manner. Expression of NLRP3 and its downstream inflammatory cytokines is reduced in the presence of HDL (p < 0.05). Furthermore, our data demonstrated that NLRP3 siRNA downregulates NLRP3 expression in mononuclear cells, thus leading to a dramatic reduction in the expression of caspase-1, IL-1β and IL-18 (p < 0.05). CONCLUSIONS: The data suggest that activation of the NLRP3 inflammasome is a critical step in caspase-1 activation and IL-1β and IL-18 secretion. Interference with the NLRP3 inflammasome can significantly inhibit the generation of cytokines, thus impeding the pathogenesis of inflammation. Termedia Publishing House 2016-07-20 2016-10-01 /pmc/articles/PMC5016581/ /pubmed/27695484 http://dx.doi.org/10.5114/aoms.2016.61356 Text en Copyright: © 2016 Termedia & Banach http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
spellingShingle Basic Research
Li, Wang Li
Hua, Li Gui
Qu, Peng
Yan, Wang Hong
Ming, Cui
Jun, Yuan Da
Yuan, Lou Da
Nan, Niu
NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis
title NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis
title_full NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis
title_fullStr NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis
title_full_unstemmed NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis
title_short NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis
title_sort nlrp3 inflammasome: a novel link between lipoproteins and atherosclerosis
topic Basic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5016581/
https://www.ncbi.nlm.nih.gov/pubmed/27695484
http://dx.doi.org/10.5114/aoms.2016.61356
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