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Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release

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dc.contributor.author Martín-Sánchez, Fátima
dc.contributor.author Martínez-García, Juan José
dc.contributor.author Muñoz-García, María
dc.contributor.author Martínez-Villanueva, Miriam
dc.contributor.author Noguera-Velasco, José A.
dc.contributor.author Andreu Martínez, David
dc.contributor.author Rivas, Luis
dc.contributor.author Pelegrín, Pablo
dc.date.accessioned 2018-11-12T11:40:14Z
dc.date.available 2018-11-12T11:40:14Z
dc.date.issued 2017
dc.identifier.citation Martín-Sánchez F, Martínez-García JJ, Muñoz-García M, Martínez-Villanueva M, Noguera-Velasco JA, Andreu D et al. Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release. Cell Death Dis. 2017 Aug 10;8(8):e2984. DOI: 10.1038/cddis.2017.390
dc.identifier.issn 2041-4889
dc.identifier.uri http://hdl.handle.net/10230/35732
dc.description.abstract The nucleotide-binding domain and leucine-rich repeat-containing receptor with a pyrin domain 3 (NLRP3) inflammasome is a sensor for different types of infections and alterations of homeostatic parameters, including abnormally high levels of the extracellular nucleotide ATP or crystallization of different metabolites. All NLRP3 activators trigger a similar intracellular pathway, where a decrease in intracellular K+ concentration and permeabilization of plasma membrane are key steps. Cationic amphipathic antimicrobial peptides and peptide toxins permeabilize the plasma membrane. In fact, some of them have been described to activate the NLRP3 inflammasome. Among them, the bee venom antimicrobial toxin peptide melittin is known to elicit an inflammatory reaction via the NLRP3 inflammasome in response to bee venom. Our study found that melittin induces canonical NLRP3 inflammasome activation by plasma membrane permeabilization and a reduction in the intracellular K+ concentration. Following melittin treatment, the apoptosis-associated speck-like protein, an adaptor protein with a caspase recruitment domain (ASC), was necessary to activate caspase-1 and induce IL-1β release. However, cell death induced by melittin prevented the formation of large ASC aggregates, amplification of caspase-1 activation, IL-18 release and execution of pyroptosis. Therefore, melittin-induced activation of the NLRP3 inflammasome results in an attenuated inflammasome response that does not result in caspase-1 dependent cell death.
dc.description.sponsorship This work was supported by SAF2015-65740-R and Subdirección General de Redes y Centros de Investigación Cooperativa-FEDER, RICET RD12/0018/0007 and RD16/0027/0010. This work was also supported by grants from the European Research Council (ERC-2013-CoG 614578 to PP) and the Instituto Salud Carlos III-Fondo Europeo de Desarrollo Regional (PI13/00174 to PP). FM-S was supported by the Sara Borrell postdoctoral grant from the Instituto Salud Carlos III (CD12/00523)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Springer Nature
dc.relation.ispartof Cell Death and Disease. 2017 Aug 10;8(8):e2984
dc.rights © Fátima Martín-Sánchez et al 2017. Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Inflamasoma
dc.subject.other Interleucina-1
dc.subject.other Melitina
dc.title Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/cddis.2017.390
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-65740-R
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/614578
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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