Interleukin-1 family precursors are cleaved by caspase-1 Authored: Ray, KP, 2010-05-17 EC Number: 3.4.22 Edited: Jupe, S, 2010-08-06 Pro-interleukin-1 beta (pro-IL1B) is the primary substrate of caspase-1. IL1B production and processing is stimulated when pathogen-associated molecular patterns (PAMPs) such as bacterial LPS are detected by cells of the innate immune system, and in response to pro-inflammatory cytokines such as TNF. Detection of PAMPs by Toll receptors leads to rapid IL1 transcription/translation and subsequent processing by caspase-1 in macrophages and monocytes. Processing is triggered by the activation of members of the NLR family and their associated inflammasome complexes. IL1B lacks a signal peptide to direct it to the Golgi for subsequent secretion, so the mode of secretion is uncertain. Once secreted, IL1B binds membrane-bound IL1 receptors, followed by recruitment of the IL1 receptor accessory protein to form a high affinity receptor complex. Ligand induced receptor activation induces the intracellular association of a number of cytosolic adapter proteins triggering intracellular signal transduction. This series of steps facilitates the induction of nuclear factor-kappa B (NFkB) and mitogen-activated protein kinase (MAPK) activity, leading to downstream transcription of additional inflammatory cytokines, including IL1B itself. A calpain-like potease has been reported to be important for the processing of pro- IL1A, but much less is known about how IL1A is released from cells and what specific roles it plays in biology. Pubmed12752666 Pubmed1574116 Pubmed8999548 Pubmed9121587 Reactome Database ID Release 43448703 Reactome, http://www.reactome.org ReactomeREACT_23804 Reviewed: Pinteaux, E, 2010-09-06 Interleukin-1 family propeptides Interleukin-1 family Interleukin-1 family N-terminal propeptides