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Interleukin-1 (IL-1) pathway.

Authors: Weber, Axel  Wasiliew, Peter  Kracht, Michael 
Citation: Weber A, etal., Sci Signal. 2010 Jan 19;3(105):cm1. doi: 10.1126/scisignal.3105cm1.
Pubmed: (View Article at PubMed) PMID:20086235
DOI: Full-text: DOI:10.1126/scisignal.3105cm1

The interleukin-1 (IL-1) family of cytokines comprises 11 proteins (IL-1F1 to IL-1F11) encoded by 11 distinct genes in humans and mice. IL-1-type cytokines are major mediators of innate immune reactions, and blockade of the founding members IL-1alpha or IL-1beta by the interleukin-1 receptor antagonist (IL-1RA) has demonstrated a central role of IL-1 in a number of human autoinflammatory diseases. IL-1alpha or IL-1beta rapidly increase messenger RNA expression of hundreds of genes in multiple different cell types. The potent proinflammatory activities of IL-1alpha and IL-1beta are restricted at three major levels: (i) synthesis and release, (ii) membrane receptors, and (iii) intracellular signal transduction. This pathway summarizes extracellular and intracellular signaling of IL-1alpha or IL-1beta, including positive- and negative-feedback mechanisms that amplify or terminate the IL-1 response. In response to ligand binding of the receptor, a complex sequence of combinatorial phosphorylation and ubiquitination events results in activation of nuclear factor kappaB signaling and the JNK and p38 mitogen-activated protein kinase pathways, which, cooperatively, induce the expression of canonical IL-1 target genes (such as IL-6, IL-8, MCP-1, COX-2, IkappaBalpha, IL-1alpha, IL-1beta, MKP-1) by transcriptional and posttranscriptional mechanisms. Of note, most intracellular components that participate in the cellular response to IL-1 also mediate responses to other cytokines (IL-18 and IL-33), Toll-like-receptors (TLRs), and many forms of cytotoxic stresses.

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CRRD Object Information
CRRD ID: 5490215
Created: 2011-09-08
Species: All species
Last Modified: 2017-01-03
Status: ACTIVE



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