title: NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India. deepakkaushiik@gmail.com
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Kaushik
authors.forename: Malvika
authors.initials: M
authors.lastname: Gupta
authors.forename: Kanhaiya Lal
authors.initials: KL
authors.lastname: Kumawat
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004664:Encephalitis Virus, Japanese / Q000378:metabolism*; D004672:Encephalitis, Japanese / Q000235:genetics* / Q000821:virology*; D007249:Inflammation; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D020170:Caspase 1