Fiche publication
Date publication
janvier 2015
Journal
Journal of immunology (Baltimore, Md. : 1950)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr VERGELY Catherine
Tous les auteurs :
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
Lien Pubmed
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.
Mots clés
Animals, Inflammation, etiology, Interleukin-1alpha, genetics, Interleukin-1beta, genetics, Mice, Mice, Knockout, Myeloid Differentiation Factor 88, genetics, Myocardial Infarction, complications, Myocarditis, etiology, Myocytes, Cardiac, immunology, Signal Transduction, genetics, Toll-Like Receptors, genetics
Référence
J. Immunol.. 2015 Jan;194(2):499-503
