Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2021 Mar 1;8:639103. doi: 10.3389/fmed.2021.639103

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

Copyright © 2021 Hirooka and Nozaki.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

PMC Copyright notice

The IL-18 signaling pathway. IL-18 is stored intracellularly as biologically inactive pro-IL-18 and is secreted extracellularly as the bioactive mature molecule after being cleaved by caspase-1. IL-18 is regulated by the endogenous inhibitor IL-18BP. Since IL-18BP has high affinity for IL-18, IL-18BP binds preferentially to IL-18 and inhibits binding to the IL-18R. IL-18 first binds to the IL-18Rα; however, this binding is low-affinity, and the IL-18Rβ chain is recruited to form a high-affinity heterodimeric complex. The activation of IL-18R recruits MyD88 to the TIR domain and anchors IRAK. Phosphorylated IRAK activates TRAF6, and which in turn phosphorylates NIK. This is followed by the activation of IKK and finally NF-κB, which initiates the transcription of target genes such as IFN-γ.