dc.contributor.author
Miteva, Kapka
dc.contributor.author
Pappritz, Kathleen
dc.contributor.author
Sosnowski, Marzena
dc.contributor.author
El-Shafeey, Muhammad
dc.contributor.author
Müller, Irene
dc.contributor.author
Dong, Fengquan
dc.contributor.author
Savvatis, Konstantinos
dc.contributor.author
Ringe, Jochen
dc.contributor.author
Tschöpe, Carsten
dc.contributor.author
Linthout, Sophie van
dc.date.accessioned
2018-06-08T10:41:42Z
dc.date.available
2018-03-16T11:05:18.843Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20898
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24197
dc.description.abstract
Inflammation in myocarditis induces cardiac injury and triggers disease
progression to heart failure. NLRP3 inflammasome activation is a newly
identified amplifying step in the pathogenesis of myocarditis. We previously
have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in
Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly
inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18
mRNA expression in CVB3-infected mice. ASC protein expression, essential for
NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated
in MSC-treated mice. Concomitantly, CVB3 infection in vitro induced NOD2
expression, NLRP3 inflammasome activation and IL-1β secretion in HL-1 cells,
which was abolished after MSC supplementation. The inhibitory effect of MSC on
NLRP3 inflammasome activity in HL-1 cells was partly mediated via secretion of
the anti-oxidative protein stanniocalcin-1. Furthermore, MSC application in
CVB3-infected mice reduced the percentage of NOD2-, ASC-, p10- and/or IL-1β-
positive splenic macrophages, natural killer cells, and dendritic cells. The
suppressive effect of MSC on inflammasome activation was associated with
normalized expression of prominent regulators of myocardial contractility and
fibrosis to levels comparable to control mice. In conclusion, MSC treatment in
myocarditis could be a promising strategy limiting the adverse consequences of
cardiac and systemic NLRP3 inflammasome activation.
en
dc.format.extent
16 Seiten
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Cardiomyopathies
en
dc.subject
Inflammasome
en
dc.subject
Mesenchymal stem cells
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::616 Krankheiten
dc.title
Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of
Coxsackievirus B3-induced inflammatory cardiomyopathy
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
2820
dcterms.bibliographicCitation.doi
10.1038/s41598-018-20686-6
dcterms.bibliographicCitation.journaltitle
Scientific Reports
dcterms.bibliographicCitation.originalpublishername
Nature Publishing Group
dcterms.bibliographicCitation.volume
8
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000029344
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000009546
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
29434214
dcterms.isPartOf.issn
2045-2322