Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-_-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-_ 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-_B (NF-_B), 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. The IL-18 signaling pathway can be freely accessed through the WikiPathways database (https://www.wikipathways.org/index.php/Pathway:WP4754).

Author Info: (1) Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India. (2) Center for Systems Biology and Molecular

Author Info: (1) Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India. (2) Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India. (3) Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India. (4) Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491, Trondheim, Norway. (5) Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India. yashwanth.subbannayya@gmail.com. Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491, Trondheim, Norway. yashwanth.subbannayya@gmail.com. (6) Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India. sneha@yenepoya.edu.in. Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491, Trondheim, Norway. sneha@yenepoya.edu.in.