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. b08IL18RAPIL-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 MEKK3IL-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 pathwayPW:0000512Pathway Ontologyinterleukin-1 signaling pathwayPW:0000883Pathway Ontologyoxidative phosphorylation pathwayPW:0001059Pathway Ontologysignaling pathway in the adaptive immune responsePW:0000820Pathway Ontology31863285PubMedA comprehensive pathway map of IL-18-mediated signalling.J Cell Commun Signal2019Rex DABAgarwal NPrasad TSKKandasamy RKSubbannayya YPinto SM