P2X 4 receptors influence inflammasome activation after spinal cord injury

Juan Pablo P de Rivero Vaccari, Dominic Bastien, Geoffrey Yurcisin, Isabelle Pineau, W. Dalton Dietrich, Yves De Koninck, Robert Keane, Steve Lacroix

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

P2X 4 and P2X 7 are the predominant purinergic P2X receptor subtypes expressed on immune and neural cells. These receptor subtypes traffic between intracellular compartments and the plasma membrane and form protein interactions with each other to regulate ATPdependent signaling. Our recent studies have shown that P2X 7 receptors in neurons and astrocytes activate NLRP1 inflammasomes, but whether P2X 4 receptors regulate inflammasome signaling is essentially unknown. Here, we demonstrate that P2X 4 receptors are expressed in neurons of the spinal cord. We provide direct evidence that spinal cord injury (SCI) induces an innate inflammatory response that leads to increased caspase-l cleavage and production of IL-1β but not IL-18. Consistent with these findings, P2X 4 knock-out mice showed impaired inflammasome signaling in the cord, resulting in decreased levels of IL-1 β and reduced infiltration of neutrophils and monocyte-derived M1 macrophages, resulting in significant tissue sparing and improvement in functional outcomes. These results indicate that P2X 4 receptors influence inflammasome signaling involving caspase-1 activation and IL-1β processing in neurons after SCI. P2X 4 might thus represent a potential therapeutic target to limit inflammatory responses associated with SCI and neurodegenerative disorders.

Original languageEnglish
Pages (from-to)3058-3066
Number of pages9
JournalJournal of Neuroscience
Volume32
Issue number9
DOIs
StatePublished - Feb 29 2012

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Inflammasomes
Spinal Cord Injuries
Interleukin-1
Neurons
Purinergic P2X Receptors
Caspase 1
Interleukin-18
Neutrophil Infiltration
Spinal Cord Diseases
Caspases
Knockout Mice
Astrocytes
Neurodegenerative Diseases
Blood Proteins
Spinal Cord
Membrane Proteins
Macrophages
Cell Membrane

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

P2X 4 receptors influence inflammasome activation after spinal cord injury. / de Rivero Vaccari, Juan Pablo P; Bastien, Dominic; Yurcisin, Geoffrey; Pineau, Isabelle; Dalton Dietrich, W.; De Koninck, Yves; Keane, Robert; Lacroix, Steve.

In: Journal of Neuroscience, Vol. 32, No. 9, 29.02.2012, p. 3058-3066.

Research output: Contribution to journalArticle

de Rivero Vaccari, Juan Pablo P ; Bastien, Dominic ; Yurcisin, Geoffrey ; Pineau, Isabelle ; Dalton Dietrich, W. ; De Koninck, Yves ; Keane, Robert ; Lacroix, Steve. / P2X 4 receptors influence inflammasome activation after spinal cord injury. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 9. pp. 3058-3066.
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