Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process

The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophage...

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Bibliographic Details
Published in:Scientific reports 2016-03, Vol.6 (1), p.22586-22586, Article 22586
Main Authors: de Torre-Minguela, Carlos, Barberà-Cremades, Maria, Gómez, Ana I., Martín-Sánchez, Fátima, Pelegrín, Pablo
Format: Article
Language:English
Subjects:
13/21
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96/95
Animals
Annexin A1 - genetics
Annexin A1 - immunology
Caspase 1 - genetics
Caspase 1 - immunology
Cytokines
Humanities and Social Sciences
Immunology
Inflammasomes
Inflammation
Inflammation - genetics
Inflammation - immunology
Inflammation - pathology
Macrophage Activation - immunology
Macrophages
Macrophages - immunology
Macrophages - pathology
Mice
Mice, Knockout
multidisciplinary
Receptors, Purinergic P2X7 - genetics
Receptors, Purinergic P2X7 - immunology
Science
Science (multidisciplinary)
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Summary:The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released after P2X7R stimulation goes beyond caspase-1 secretome. The characterization of P2X7R-secretome reveals a new function of this receptor through a fine-tuning of protein release. We found that P2X7R stimulation in macrophages is able to release potent anti-inflammatory proteins, such as Annexin A1, independently of their polarization state suggesting for first time a potential role for P2X7R during resolution of the inflammation and not linked to the release of pro-inflammatory cytokines. These results are of prime importance for the development of therapeutics targeting P2X7R.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep22586