Cutting edge: IL-1α is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction.

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Ressource 1Télécharger: BIB_3740D52D64AE.P001.pdf (1126.40 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_3740D52D64AE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Cutting edge: IL-1α is a crucial danger signal triggering acute myocardial inflammation during myocardial infarction.
Périodique
Journal of Immunology
Auteur(s)
Lugrin J., Parapanov R., Rosenblatt-Velin N., Rignault-Clerc S., Feihl F., Waeber B., Müller O., Vergely C., Zeller M., Tardivel A., Schneider P., Pacher P., Liaudet L.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
194
Numéro
2
Pages
499-503
Langue
anglais
Résumé
Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-κB in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88(-/-) fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1α, but not IL-1β, and the immune activation of cardiac fibroblasts was abrogated by an IL-1R antagonist and an IL-1α-blocking Ab. Moreover, immune responses triggered by necrotic Il1a(-/-) cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1α in the plasma, and postischemic inflammation was attenuated in Il1a(-/-) mice. Thus, our findings identify IL-1α as a crucial early danger signal triggering post-MI inflammation.
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/12/2014 13:57
Dernière modification de la notice
08/05/2019 17:04
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