| http://purl.uniprot.org/citations/34815792 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34815792 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.org/dc/terms/identifier | "doi:10.7150/thno.59418"xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Tapia E."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Galvez E.M."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Pardo J."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Arias M."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Bird P.I."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Santiago L."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Roig F.J."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Esteban P."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Ramirez-Labrada A."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Uranga-Murillo I."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Garzon-Tituana M."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/author | "Pesini C."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/name | "Theranostics"xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/pages | "9873-9883"xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/title | "Biological relevance of Granzymes A and K during E. coli sepsis."xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://purl.uniprot.org/core/volume | "11"xsd:string |
| http://purl.uniprot.org/citations/34815792 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/34815792 |
| http://purl.uniprot.org/citations/34815792 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/34815792 |
| http://purl.uniprot.org/uniprot/#_P11032-mappedCitation-34815792 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34815792 |
| http://purl.uniprot.org/uniprot/#_A4FUV8-mappedCitation-34815792 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34815792 |
| http://purl.uniprot.org/uniprot/#_O35205-mappedCitation-34815792 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/34815792 |