Interleukin-1 Family Cytokines in Liver Diseases

Figure 3

Processing enzymes dependent on and independent of the inflammasome. Caspase-1 is an enzyme that putatively converts IL-1β and IL-18. Caspase-1 is produced as zymogen and requires cleavage. Inflammasomes are the machinery in which caspase-1, IL-1β, and IL-18 are processed. Inflammasomes are classified as canonical and noncanonical. Canonical inflammasomes can be divided into 4 main types based on differences in cytoplasmic PRRs, such as NLRP1, NLRP3, NLRC4, and AIM. Noncanonical inflammasomes activate caspase-11, caspase-8, caspase-4, and caspase-5 and often collaborate with the canonical inflammasomes. Monocyte-macrophage lineage cells, dendritic cells, and neutrophils can harbor inflammasomes. Various enzymes have the capacity to process IL-1β and IL-18 extracellularly. Neutrophil-derived proteinase 3, mast cell chymase, granzyme B produced by NK cells, and meprins produced by epithelial cells can convert pro-IL-1β and pro-IL-18 into mature ligands. AIM: absent in melanoma 2; NK: natural killer; NLRC: NACHT, leucine-rich repeat, and caspase recruitment domain-containing protein; NLRP: NACHT, leucine-rich repeat, and pyrin domain-containing protein; PRR: pattern recognition receptor.