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

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 dif...

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Autores: Martín-Sánchez, Fátima, Martínez-García, Juan José, Muñoz-García, María, Martínez-Villanueva, Miriam, Noguera-Velasco, José A., Andreu Martínez, David, Rivas, Luis, Pelegrín, Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/35732
Acceso en línea:http://hdl.handle.net/10230/35732
http://dx.doi.org/10.1038/cddis.2017.390
Access Level:acceso abierto
Palabra clave:Inflamasoma
Interleucina-1
Melitina
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spelling Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β releaseMartín-Sánchez, FátimaMartínez-García, Juan JoséMuñoz-García, MaríaMartínez-Villanueva, MiriamNoguera-Velasco, José A.Andreu Martínez, DavidRivas, LuisPelegrín, PabloInflamasomaInterleucina-1MelitinaThe 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.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)Springer Nature201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/35732http://dx.doi.org/10.1038/cddis.2017.390reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésCell Death and Disease. 2017 Aug 10;8(8):e2984info:eu-repo/grantAgreement/ES/1PE/SAF2015-65740-Rinfo:eu-repo/grantAgreement/EC/FP7/614578© 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 Licensehttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/357322026-06-12T07:21:37Z
dc.title.none.fl_str_mv Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
title Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
spellingShingle Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
Martín-Sánchez, Fátima
Inflamasoma
Interleucina-1
Melitina
title_short Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
title_full Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
title_fullStr Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
title_full_unstemmed Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
title_sort Lytic cell death induced by melittin bypasses pyroptosis but induces NLRP3 inflammasome activation and IL-1β release
dc.creator.none.fl_str_mv Martín-Sánchez, Fátima
Martínez-García, Juan José
Muñoz-García, María
Martínez-Villanueva, Miriam
Noguera-Velasco, José A.
Andreu Martínez, David
Rivas, Luis
Pelegrín, Pablo
author Martín-Sánchez, Fátima
author_facet Martín-Sánchez, Fátima
Martínez-García, Juan José
Muñoz-García, María
Martínez-Villanueva, Miriam
Noguera-Velasco, José A.
Andreu Martínez, David
Rivas, Luis
Pelegrín, Pablo
author_role author
author2 Martínez-García, Juan José
Muñoz-García, María
Martínez-Villanueva, Miriam
Noguera-Velasco, José A.
Andreu Martínez, David
Rivas, Luis
Pelegrín, Pablo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Inflamasoma
Interleucina-1
Melitina
topic Inflamasoma
Interleucina-1
Melitina
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/35732
http://dx.doi.org/10.1038/cddis.2017.390
url http://hdl.handle.net/10230/35732
http://dx.doi.org/10.1038/cddis.2017.390
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Cell Death and Disease. 2017 Aug 10;8(8):e2984
info:eu-repo/grantAgreement/ES/1PE/SAF2015-65740-R
info:eu-repo/grantAgreement/EC/FP7/614578
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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