Interleukin-1 Family Cytokines in Liver Diseases

Figure 1

IL-1 family agonists and antagonists. The IL-1 family is divided into three subfamilies based on the length of the N-terminal pro-pieces. The IL-1 subfamily consists of IL-1α, IL-β, IL-1 receptor antagonist (IL-1Ra), and IL-33. The IL-18 subfamily is composed of IL-18 and IL-37. IL-36α, IL-36β, IL-36γ, and IL-38 belong to the IL-36 subfamily. The receptor for each IL-1 family cytokine is a heterodimer of the proper or common subunits. IL-1R1, ST2, IL-18Rα, and IL-36R are ligand-binding subunits, whereas IL-1R accessory protein (IL-1LRAcP), IL-18Rβ, and SIGIRR (TIR8) are signaling subunits. Upon engagement of the binding subunits with the corresponding ligands, they recruit the corresponding signaling receptor subunit, which, except in IL-37 signaling, ultimately translocates nuclear factor- (NF-) κB to the nucleus and activates MAPKs such as p38 and JNK. IL-38, IL-1Ra, IL-18-binding protein (IL-18BP), and IL-36Ra inhibit IL-36, IL-1, IL-18, and IL-36 signaling, respectively. IL-37 inhibits the signal pathways of the innate and acquired immune responses via mechanisms that are poorly identified. IL-1R2 acts as a decoy receptor for IL-1α and IL-1β. Stop signs indicate proteins that inhibit corresponding ligand signaling or those that negatively regulate other signal pathways as well. JNK: c-jun-N-terminal kinase; MAPK: mitogen-activated protein kinase; SIGIRR: single immunoglobulin IL-1-related receptor; ST2: suppression of tumorigenicity 2.