A comprehensive pathway map of IL-18-mediated signalling

Area of Science:

• Immunology
• Molecular Biology
• Systems Biology

Background:

• Interleukin-18 (IL-18) is a crucial cytokine in the IL-1 family, known for inducing Interferon-gamma (IFN-γ).
• IL-18 signaling activates key pathways like Nuclear Factor-kappa B (NF-κB) and Mitogen-Activated Protein Kinases (MAPKs), influencing immune responses and inflammation.
• A comprehensive resource detailing the IL-18 signaling pathway was previously unavailable.

Purpose of the Study:

• To develop and present an integrated pathway map for Interleukin-18/Interleukin-18 Receptor (IL-18/IL-18R) signaling.
• To provide a centralized, curated resource for researchers studying IL-18-mediated biological processes.
• To facilitate further investigation into the complex roles of IL-18 in immunity, inflammation, and tissue regeneration.

Main Methods:

• Literature mining of published scientific articles.
• Manual curation of data based on established guidelines (NetPath).
• Integration of various molecular events including protein-protein interactions, enzyme catalysis, translocations, activations/inhibitions, transcriptional regulation, and gene/protein expression.

Main Results:

• Development of a comprehensive IL-18/IL-18R signaling pathway map.
• The map details 16 protein-protein interactions, 38 enzyme-catalysis events, 12 protein translocations, 26 activation/inhibition events, and 230 gene regulation events.
• 84 induced protein expression events were identified and mapped.

Conclusions:

• The developed IL-18 signaling pathway map provides a valuable resource for understanding IL-18's role in host defense and inflammation.
• This integrated map can serve as a foundation for future research into IL-18-related diseases and therapeutic strategies.
• The pathway map is publicly accessible via the WikiPathways database for broad scientific use.