P2X7 receptor differentially couples to distinct release pathways for IL-1b in mouse macrophage

Pelegrin, Pablo; Barroso-Gutierrez, Consuelo; Surprenant, Annmarie

Publication:
P2X7 receptor differentially couples to distinct release pathways for IL-1b in mouse macrophage

dc.contributor.author	Pelegrin, Pablo
dc.contributor.author	Barroso-Gutierrez, Consuelo
dc.contributor.author	Surprenant, Annmarie
dc.contributor.department	Bioquímica y Biología Molecular B e Inmunología
dc.date.accessioned	2024-01-25T09:28:48Z
dc.date.available	2024-01-25T09:28:48Z
dc.date.issued	2008
dc.description.abstract	The pro-inflammatory IL-1 cytokines, IL-1a, IL-1b and IL-18, are key mediators of the acute immune response to injury and infection. Mechanisms underlying their cellular release remain unclear. Activation of purinergic P2X7 receptors (P2X7R) by extracellular ATP is a key physiological inducer of rapid IL-1brelease from LPS-primed macrophage. We investigated patterns of ATP-mediated release of IL-1 cytokines from three macrophage types in attempts to provide direct evidence for or against distinct release mechanisms. We used peritoneal macrophage from P2X7R-/- mice and found that release of IL-1a, IL-18, as well as IL-1b, by ATP resulted exclusively from activation of P2X7R, that release of all these IL-1 cytokines involved pannexin-1 (panx1), and that there was both a panx1-dependent and independent component to IL-1b release. We compared IL-1 release patterns from LPS-primed peritoneal macrophage, RAW264.7 macrophage and J774A.1 macrophage. We found RAW264.7 macrophage readily release pro-IL- 1b independently of panx1 but do not release mature IL-1b because they do not express apoptotic speck-like protein with a caspase-activating recruiting domain (ASC) and so have no caspase-1 inflammasome activity. We delineated two distinct release pathways: the well-known caspase-1 cascade mediating release of processed IL-1b that was selectively blocked by inhibition of caspase-1 or panx1, and a calcium-independent, caspase-1/panx1-independent release of pro-IL-1b that was selectively blocked by glycine. None of these release responses were associated with cell damage or cytolytic effects. This provides the first direct demonstration of a distinct signaling mechanism responsible for ATP-induced release of pro-IL-1b.	es
dc.format	application/pdf	es
dc.format.extent	39	es
dc.identifier.citation	The Journal of Immunology, volumen 180, nº 11, año 2008, páginas 7147-7157
dc.identifier.doi	10.4049/jimmunol.180.11.7147
dc.identifier.uri	http://hdl.handle.net/10201/137734
dc.language	eng	es
dc.publisher	The American Association of Immunologists, Inc.	es
dc.relation	Wellcome Trust y AstraZeneca Charnwood, UK	es
dc.relation.publisherversion	https://journals.aai.org/jimmunol/article/180/11/7147/84652/P2X7-Receptor-Differentially-Couples-to-Distinct	es
dc.rights.accessRights	info:eu-repo/semantics/restrictedAccess
dc.subject	Ratones	es
dc.subject	Macrófagos	es
dc.subject	Citocinas	es
dc.subject	LPS	es
dc.subject	Inflamación	es
dc.subject.other	CDU::6 - Ciencias aplicadas	es
dc.title	P2X7 receptor differentially couples to distinct release pathways for IL-1b in mouse macrophage	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es