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- 2018
A Review of Interleukin-1 in Heart Disease: Where Do We Stand Today?DOI: 10.1007/s40119-018-0104-3 Keywords: Anakinra, Arrhythmia, Canakinumab, Heart failure, Interleukin-1, Myocardial infarction, Myocarditis, Pericarditis, Sepsis-induced cardiomyopathy Abstract: IL-1β synthesis and secretion. IL-1β binds to the IL-1 receptor type 1 (IL-1R1). Then the co-receptor chain, termed the accessory protein (IL-1RAcP), is recruited. This triple complex recruits the adaptor protein MyD88 to the Toll-IL-1 receptor (TIR) domain. Several kinases are phosphorylated, nuclear factor-κB (NF-κB) translocates to the nucleus, and pro-ILβ transcription ensues. The NLRP3-inflammasome is a cytosolic molecular structure composed of an adaptor protein, pro-caspase 1, and the NLRP3 sensor molecule, which may be activated by both infectious stimuli, known as pathogen-associated molecular patterns (PAMPs) and sterile stimuli, known as damage-associated molecular patterns (DAMPs). This activation is based on either ATP binding to the P2X7 receptor with a secondary efflux of potassium to the extracellular space or reactive oxygen species (ROS) formation. Upon activation of the NLRP3-inflammasome, pro-caspase-1 is converted to an active enzyme. Active caspase-1 then cleaves the IL-1 precursor in specialized secretory lysosomes or in the cytosol, followed by secretion of “mature” IL-1
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