A Review of Interleukin-1 in Heart Disease: Where Do We Stand Today?

Fig. 1. 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-1β