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Sci. Signal., 19 January 2010
Vol. 3, Issue 105, p. cm1
[DOI: 10.1126/scisignal.3105cm1]

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Interleukin-1 (IL-1) Pathway

Axel Weber1, Peter Wasiliew1, and Michael Kracht1*

1 Rudolf-Buchheim-Institute of Pharmacology, Justus-Liebig-University Giessen, 35392 Giessen, Germany.

Abstract: 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-1{alpha} or IL-1β by the interleukin-1 receptor antagonist (IL-1RA) has demonstrated a central role of IL-1 in a number of human autoinflammatory diseases. IL-1{alpha} or IL-1β rapidly increase messenger RNA expression of hundreds of genes in multiple different cell types. The potent proinflammatory activities of IL-1{alpha} and IL-1β 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-1{alpha} or IL-1β, 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 {kappa}B 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, I{kappa}B{alpha}, IL-1{alpha}, IL-1β, 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.

* Corresponding author. E-mail, michael.kracht{at}pharma.med.uni-giessen.de

Citation: A. Weber, P. Wasiliew, M. Kracht, Interleukin-1 (IL-1) Pathway. Sci. Signal. 3, cm1 (2010).

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