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

ABSTRACT: 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-?B 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-1?, but not IL-1?, and the immune activation of cardiac fibroblasts was abrogated by an IL-1R antagonist and an IL-1?-blocking Ab. Moreover, immune responses triggered by necrotic Il1a(-/-) cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1? in the plasma, and postischemic inflammation was attenuated in Il1a(-/-) mice. Thus, our findings identify IL-1? as a crucial early danger signal triggering post-MI inflammation.

SUBMITTER: Lugrin J 

PROVIDER: S-EPMC4278196 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature