PMID- 22393394
OWN - NLM
STAT- MEDLINE
DCOM- 20120723
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 2
DP  - 2012
TI  - NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese 
      encephalitis.
PG  - e32270
LID - 10.1371/journal.pone.0032270 [doi]
LID - e32270
AB  - 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 beta (IL-1beta) 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-1beta 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-1beta and IL-18 maturation.
FAU - Kaushik, Deepak Kumar
AU  - Kaushik DK
AD  - National Brain Research Centre, Manesar, Haryana, India. deepakkaushiik@gmail.com
FAU - Gupta, Malvika
AU  - Gupta M
FAU - Kumawat, Kanhaiya Lal
AU  - Kumawat KL
FAU - Basu, Anirban
AU  - Basu A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120229
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*genetics/*physiology
MH  - Caspase 1/metabolism
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Encephalitis Virus, Japanese/*metabolism
MH  - Encephalitis, Japanese/*genetics/*virology
MH  - Inflammation
MH  - Interleukin-18/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Microglia/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Protein Structure, Tertiary
MH  - Reactive Oxygen Species
MH  - Signal Transduction
PMC - PMC3290554
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/03/07 06:00
MHDA- 2012/07/24 06:00
PMCR- 2012/02/29
CRDT- 2012/03/07 06:00
PHST- 2011/11/01 00:00 [received]
PHST- 2012/01/24 00:00 [accepted]
PHST- 2012/03/07 06:00 [entrez]
PHST- 2012/03/07 06:00 [pubmed]
PHST- 2012/07/24 06:00 [medline]
PHST- 2012/02/29 00:00 [pmc-release]
AID - PONE-D-11-21907 [pii]
AID - 10.1371/journal.pone.0032270 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(2):e32270. doi: 10.1371/journal.pone.0032270. Epub 2012 Feb 29.