Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated T-helper (Th)1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through its binding to the IL-18 receptor complex and activation of nuclear factor-κB (NF-κB), culminating in the production and release of several cytokines, chemokines, and cellular adhesion molecules. In certain cell types, IL-18 also activates mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase/ AKT serine/threonine kinase (PI3K/AKT) signaling modules leading to the production and release of proinflammatory cytokines. IL-18-mediated signaling acts as one of the vital components of the immunomodulatory cytokine networks involved in host defense, inflammation, and tissue regeneration. Albeit its biomedical importance, a comprehensive resource of IL-18 mediated signaling pathway is currently lacking. In this study, we report on the development of an integrated pathway map of IL-18/IL-18R signaling. The pathway map was developed through literature mining from published literature based on manual curation guidelines adapted from NetPath and includes information on 16 protein-protein interaction events, 38 enzyme-catalysis events, 12 protein translocation events, 26 activations/inhibition events, transcriptional regulators, 230 gene regulation events and 84 induced protein expression events. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-γ-inducing factor derived from anti-CD3-stimulated Th1 cells. IL-18 plays a significant role in the activation of hematopoietic cell types mediating both Th1 and Th2 responses and is the primary inducer of interferon-γ in these cells. The biological activity of IL-18 is mediated through its binding to the IL-18 receptor complex (IL-18R) and activation of nuclear factor-kB (NF-kB), culminating in the production and release of several cytokines, chemokines, and cellular adhesion molecules. In certain cell types, IL-18 also activates mitogen-activated protein kinases (MAPKs) and PI3K/AKT signaling modules leading to the production and release of proinflammatory cytokines. IL-18 mediated signaling acts as one of the vital components of the immunomodulatory cytokine networks involved in host defense, inflammation, and tissue regeneration. b08 IL18RAP IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the interaction of IL-1RAcP with IL-1 alpha and type 1 IL-1 receptor complex in Sw3T3 fibroblasts and the CHO-IR/AcP cells. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the interaction of MAP3K3 and TRAF6 in mouse embryonic fibroblasts(MEF) cells. RING and zinc finger domains of TRAF6 were involved in the activation of MEKK3 IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. IL-1 stimulates the recruitment of IRAK1 to IL-1 receptor complex, followed by interaction of activated IRAK1 with TRAF6 in 293T cells, leading to NFKB activation. Interleukin mediated signaling pathway PW:0000512 Pathway Ontology interleukin-1 signaling pathway PW:0000883 Pathway Ontology oxidative phosphorylation pathway PW:0001059 Pathway Ontology signaling pathway in the adaptive immune response PW:0000820 Pathway Ontology 31863285 PubMed A comprehensive pathway map of IL-18-mediated signalling. J Cell Commun Signal 2019 Rex DAB Agarwal N Prasad TSK Kandasamy RK Subbannayya Y Pinto SM