Journal
JOURNAL OF CELL COMMUNICATION AND SIGNALING
Volume 14, Issue 2, Pages 257-266Publisher
SPRINGER
DOI: 10.1007/s12079-019-00544-4
Keywords
Inflammation; Proinflammatory cytokine; Post-translational modifications; Protein-protein interactions; Signaling pathways
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Funding
- Karnataka Biotechnology and Information Technology Services (KBITS), Government of Karnataka [ITD 02 MDA 2017]
- Indian Council of Medical Research (ICMR), Government of India
- INSPIRE Faculty Award from the Department of Science and Technology (DST), Government of India
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Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and was initially described as an IFN-gamma-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-gamma 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-kappa B (NF-kappa 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).
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