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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Uranga-Murillo, Iratxe | - |
dc.contributor.author | Tapia-Casellas, Elena | - |
dc.contributor.author | Garzón-Tituana, Marcela | - |
dc.contributor.author | Ramírez-Labrada, Ariel | - |
dc.contributor.author | Santiago, Llipsy | - |
dc.contributor.author | Pesini, Cecilia | - |
dc.contributor.author | Esteban, Patricia | - |
dc.contributor.author | Roig, Francisco J. | - |
dc.contributor.author | Galvez, Eva M. | - |
dc.contributor.author | Bird, Phillip Ian | - |
dc.contributor.author | Pardo, Julián | - |
dc.contributor.author | Arias, Maykel | - |
dc.date.accessioned | 2022-05-13T09:52:01Z | - |
dc.date.available | 2022-05-13T09:52:01Z | - |
dc.date.issued | 2021-10-17 | - |
dc.identifier.citation | Uranga-Murillo I, Tapia E, Garzón-Tituaña M, Ramirez-Labrada A, Santiago L, Pesini C, Esteban P, Roig FJ, Galvez EM, Bird PI, Pardo J, Arias M. Biological relevance of Granzymes A and K during E. coli sepsis. Theranostics 2021; 11(20):9873-9883. doi:10.7150/thno.59418. Available from https://www.thno.org/v11p9873.htm | es_ES |
dc.identifier.issn | 1838-7640 | es_ES |
dc.identifier.uri | https://repositorio.usj.es/handle/123456789/784 | - |
dc.description.abstract | Aims: Recent in vitro findings suggest that the serine protease Granzyme K (GzmK) may act as a proinflammatory mediator. However, its role in sepsis is unknown. Here we aim to understand the role of GzmK in a mouse model of bacterial sepsis and compare it to the biological relevance of Granzyme A (GzmA). Methods: Sepsis was induced in WT, GzmA-/- and GzmK-/- mice by an intraperitoneal injection of 2x108 CFU from E. coli. Mouse survival was monitored during 5 days. Levels of IL-1α, IL-1β, TNFα and IL-6 in plasma were measured and bacterial load in blood, liver and spleen was analyzed. Finally, profile of cellular expression of GzmA and GzmK was analyzed by FACS. Results: GzmA and GzmK are not involved in the control of bacterial infection. However, GzmA and GzmK deficient mice showed a lower sepsis score in comparison with WT mice, although only GzmA deficient mice exhibited increased survival. GzmA deficient mice also showed reduced expression of some proinflammatory cytokines like IL1-α, IL-β and IL-6. A similar result was found when extracellular GzmA was therapeutically inhibited in WT mice using serpinb6b, which improved survival and reduced IL-6 expression. Mechanistically, active extracellular GzmA induces the production of IL-6 in macrophages by a mechanism dependent on TLR4 and MyD88. Conclusions: These results suggest that although both proteases contribute to the clinical signs of E. coli-induced sepsis, inhibition of GzmA is sufficient to reduce inflammation and improve survival irrespectively of the presence of other inflammatory granzymes, like GzmK. | es_ES |
dc.format.extent | 11 p. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | IVYSPRING INT PUBLPO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA | es_ES |
dc.relation | The authors would like to thank the animal care staff and Servicios Cientifico Tecnicos del CIBA (IACS-University of Zaragoza) and Servicios de Apoyo a la Investigacion (University of Zaragoza) for the assistance during the experiments. This work was supported by grant SAF2017-83120-C2-1-R and PID2020-113963RBI00 from the Ministry of Science, Innovation and Universities and FEDER (Group B29_17R, Aragon Government). IU-M, MG-T and CP were supported by a PhD fellowships from Aragon Government, Ministry of Science, Innovation and Universities (FPI) and Asociacion Espanola contra el Cancer (AECC). MA and LS were supported by a post-doctoral fellowship "Juan de la Cierva-formacion" (MA, LS) and "Juan de la Cierva-incorporacion" (MA) from the Ministry of Science, Innovation and Universities. JP was supported by ARAID Foundation. | es_ES |
dc.relation.requires | Adobe pdf | es_ES |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Granzyme K | es_ES |
dc.subject | Granzyme A | es_ES |
dc.subject | Bacterial sepsis | es_ES |
dc.subject | Inflammation | es_ES |
dc.title | Biological relevance of Granzymes A and K during E. coli sepsis | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | https://www.thno.org/v11p9873.htm | es_ES |
dc.identifier.publicationfirstpage | 9873 | es_ES |
dc.identifier.publicationlastpage | 9883 | es_ES |
dc.identifier.doi | 10.7150/thno.59418 | es_ES |
dc.rights.accessrights | info:eu-repo/semantics/openAccess | es_ES |
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