MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author Vandendriessche, Benjaminca
- dc.contributor.author Goethals, Anca
- dc.contributor.author Simats, Albaca
- dc.contributor.author Hamme, Evelien Vanca
- dc.contributor.author Brouckaert, Peterca
- dc.contributor.author Cauwels, Anjeca
- dc.date.accessioned 2015-03-24T12:08:00Z
- dc.date.available 2015-03-24T12:08:00Z
- dc.date.issued 2014ca
- dc.description.abstract Background: MAPK-activated protein kinase 2 (MK2) plays a pivotal role in the cell response to (inflammatory) stress. Among others, MK2 is known to be involved in the regulation of cytokine mRNA metabolism and regulation of actin cytoskeleton dynamics. Previously, MK2-deficient mice were shown to be highly resistant to LPS/D-Galactosamine-induced hepatitis. Additionally, research in various disease models has indicated the kinase as an interesting inhibitory drug target for various acute or chronic inflammatory diseases. Results: We show that in striking contrast to the known resistance of MK2-deficient mice to a challenge with LPS/D-Gal, a low dose of tumor necrosis factor (TNF) causes hyperacute mortality via an oxidative stress driven mechanism. We identified in vivo defects in the stress fiber response in endothelial cells, which could have resulted in reduced resistance of the endothelial barrier to deal with exposure to oxidative stress. In addition, MK2-deficient mice were found to be more sensitive to cecal ligation and puncture-induced sepsis. Conclusions: The capacity of the endothelial barrier to deal with inflammatory and oxidative stress is imperative to allow a regulated immune response and maintain endothelial barrier integrity. Our results indicate that, considering the central role of TNF in pro-inflammatory signaling, therapeutic strategies examining pharmacological inhibition of MK2 should take potentially dangerous side effects at the level of endothelial barrier integrity into account.en
- dc.description.sponsorship Research was supported by the agency for Innovation by Science and Technology (IWT); Research Foundation Flanders (FWO); and Ghent University: Concerted Research Actions (GOA)en
- dc.format.mimetype application/pdfca
- dc.identifier.citation Vandendriessche B, Goethals A, Simats A, Van Hamme E, Brouckaert P, Cauwels A. MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock. BMC Physiology. 2014;14:5. DOI: 10.1186/s12899-014-0005-1ca
- dc.identifier.doi http://dx.doi.org/10.1186/s12899-014-0005-1
- dc.identifier.issn 1472-6793ca
- dc.identifier.uri http://hdl.handle.net/10230/23266
- dc.language.iso engca
- dc.publisher BioMed Centralca
- dc.relation.ispartof BMC Physiology. 2014;14:5
- dc.rights © 2014 Vandendriessche et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri http://creativecommons.org/licenses/by/4.0
- dc.subject.keyword MK2en
- dc.subject.keyword Inflammatory shocken
- dc.subject.keyword Tumor necrosis factoren
- dc.subject.keyword Reactive oxygen speciesen
- dc.subject.keyword Actin cytoskeletonen
- dc.subject.keyword Endothelial permeabilityen
- dc.subject.keyword Cecal ligation and punctureen
- dc.subject.other Proteïnes quinasesca
- dc.subject.other Regulació cel·lularca
- dc.subject.other RNA missatgerca
- dc.title MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shockca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca