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Article Dans Une Revue Journal of Immunology Année : 2016

Cutting Edge: IL-1α Is a Crucial Danger Signal Triggering Acute Myocardial Inflammation during Myocardial Infarction

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Résumé

Myocardial infarction (MI) induces a sterile inflammatory response which contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile pro-inflammatory signal activating MAP kinases 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 the implication 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-1 receptor antagonist and an IL-1α blocking antibody. Moreover, immune responses triggered by necrotic Il1a −/− cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1α in the plasma, and post-ischemic inflammation was attenuated in Il1a −/− mice. Thus, our findings identify IL-1α as a crucial early danger signal triggering post-MI inflammation.
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Dates et versions

hal-03434163 , version 1 (18-11-2021)

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Jérôme Lugrin, Roumen Parapanov, Nathalie Rosenblatt-Velin, Stéphanie Rignault-Clerc, François Feihl, et al.. Cutting Edge: IL-1α Is a Crucial Danger Signal Triggering Acute Myocardial Inflammation during Myocardial Infarction. Journal of Immunology, 2016, 194, pp.499 - 503. ⟨10.4049/jimmunol.1401948⟩. ⟨hal-03434163⟩
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