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A comprehensive pathway map of IL-18-mediated signalling

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Journal of Cell Communication and Signaling Aims and scope


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. The IL-18 signaling pathway can be freely accessed through the WikiPathways database (

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Fig. 1





Interferon gamma




Macrophage colony-stimulating factor


Nuclear factor-κB


Protein-protein interaction


Interleukin-18 binding protein


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We thank Karnataka Biotechnology and Information Technology Services (KBITS), Government of Karnataka, for the support to Center for Systems Biology and Molecular Medicine at Yenepoya (Deemed to be University) under the Biotechnology Skill Enhancement Programme in Multiomics Technology (BiSEP GO ITD 02 MDA 2017). RDAB is a recipient of the Senior Research Fellowship from the Indian Council of Medical Research (ICMR), Government of India. SMP is a recipient of the INSPIRE Faculty Award from the Department of Science and Technology (DST), Government of India.

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Correspondence to Yashwanth Subbannayya or Sneha M. Pinto.

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Rex, D., Agarwal, N., Prasad, T.S.K. et al. A comprehensive pathway map of IL-18-mediated signalling. J. Cell Commun. Signal. 14, 257–266 (2020).

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