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NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis

BACKGROUND: Japanese Encephalitis virus (JEV) is a common cause of acute and epidemic viral encephalitis. JEV infection is associated with microglial activation resulting in the production of pro-inflammatory cytokines including Interleukin-1 β (IL-1β) and Interleukin-18 (IL-18). The Pattern Recogni...

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Autores principales: Kaushik, Deepak Kumar, Gupta, Malvika, Kumawat, Kanhaiya Lal, Basu, Anirban
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290554/
https://www.ncbi.nlm.nih.gov/pubmed/22393394
http://dx.doi.org/10.1371/journal.pone.0032270
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author Kaushik, Deepak Kumar
Gupta, Malvika
Kumawat, Kanhaiya Lal
Basu, Anirban
author_facet Kaushik, Deepak Kumar
Gupta, Malvika
Kumawat, Kanhaiya Lal
Basu, Anirban
author_sort Kaushik, Deepak Kumar
collection PubMed
description BACKGROUND: Japanese Encephalitis virus (JEV) is a common cause of acute and epidemic viral encephalitis. JEV infection is associated with microglial activation resulting in the production of pro-inflammatory cytokines including Interleukin-1 β (IL-1β) and Interleukin-18 (IL-18). The Pattern Recognition Receptors (PRRs) and the underlying mechanism by which microglia identify the viral particle leading to the production of these cytokines is unknown. METHODOLOGY/PRINCIPAL FINDINGS: For our studies, we have used murine model of JEV infection as well as BV-2 mouse microglia cell line. In this study, we have identified a signalling pathway which leads to the activation of caspase-1 as the key enzyme responsible for the maturation of both IL-1β and IL-18 in NACHT, LRR and PYD domains-containing protein-3 (NLRP3) dependent manner. Depletion of NLRP3 results in the reduction of caspase-1 activity and subsequent production of these cytokines. CONCLUSION/SIGNIFICANCE: Our results identify a mechanism mediated by Reactive Oxygen Species (ROS) production and potassium efflux as the two danger signals that link JEV infection to caspase-1 activation resulting in subsequent IL-1β and IL-18 maturation.
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spelling pubmed-32905542012-03-05 NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis Kaushik, Deepak Kumar Gupta, Malvika Kumawat, Kanhaiya Lal Basu, Anirban PLoS One Research Article BACKGROUND: Japanese Encephalitis virus (JEV) is a common cause of acute and epidemic viral encephalitis. JEV infection is associated with microglial activation resulting in the production of pro-inflammatory cytokines including Interleukin-1 β (IL-1β) and Interleukin-18 (IL-18). The Pattern Recognition Receptors (PRRs) and the underlying mechanism by which microglia identify the viral particle leading to the production of these cytokines is unknown. METHODOLOGY/PRINCIPAL FINDINGS: For our studies, we have used murine model of JEV infection as well as BV-2 mouse microglia cell line. In this study, we have identified a signalling pathway which leads to the activation of caspase-1 as the key enzyme responsible for the maturation of both IL-1β and IL-18 in NACHT, LRR and PYD domains-containing protein-3 (NLRP3) dependent manner. Depletion of NLRP3 results in the reduction of caspase-1 activity and subsequent production of these cytokines. CONCLUSION/SIGNIFICANCE: Our results identify a mechanism mediated by Reactive Oxygen Species (ROS) production and potassium efflux as the two danger signals that link JEV infection to caspase-1 activation resulting in subsequent IL-1β and IL-18 maturation. Public Library of Science 2012-02-29 /pmc/articles/PMC3290554/ /pubmed/22393394 http://dx.doi.org/10.1371/journal.pone.0032270 Text en Kaushik et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kaushik, Deepak Kumar
Gupta, Malvika
Kumawat, Kanhaiya Lal
Basu, Anirban
NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis
title NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis
title_full NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis
title_fullStr NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis
title_full_unstemmed NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis
title_short NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis
title_sort nlrp3 inflammasome: key mediator of neuroinflammation in murine japanese encephalitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290554/
https://www.ncbi.nlm.nih.gov/pubmed/22393394
http://dx.doi.org/10.1371/journal.pone.0032270
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