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


Autoria(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.
Data(s)

2015

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_3740D52D64AE

isbn:1550-6606 (Electronic)

pmid:25505286

doi:10.4049/jimmunol.1401948

isiid:000347176700002

Idioma(s)

en

Fonte

Journal of Immunology, vol. 194, no. 2, pp. 499-503

Tipo

info:eu-repo/semantics/article

article