Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sci. Signal., 19 January 2010
Vol. 3, Issue 105, p. cm1
[DOI: 10.1126/scisignal.3105cm1]
CONNECTIONS MAP OVERVIEWS
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 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 or IL-1β rapidly increase messenger RNA expression of hundreds of genes in multiple different cell types. The potent proinflammatory activities of IL-1 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 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 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, IB, IL-1, 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.
IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells.
S. Z. Ben-Sasson, A. Hogg, J. Hu-Li, P. Wingfield, X. Chen, M. Crank, S. Caucheteux, M. Ratner-Hurevich, J. A. Berzofsky, R. Nir-Paz, et al. (2013)
J. Exp. Med.
210, 491-502
|Abstract »|Full Text »|PDF »
Lysine 63-linked Ubiquitination Modulates Mixed Lineage Kinase-3 Interaction with JIP1 Scaffold Protein in Cytokine-induced Pancreatic {beta} Cell Death.
R. K. Humphrey, S. M. A. Yu, A. Bellary, S. Gonuguntla, M. Yebra, and U. S. Jhala (2013)
J. Biol. Chem.
288, 2428-2440
|Abstract »|Full Text »|PDF »
Delayed Resolution of Lung Inflammation in Il-1rn-/- Mice Reflects Elevated IL-17A/Granulocyte Colony-Stimulating Factor Expression.
K. M. Hudock, Y. Liu, J. Mei, R. C. Marino, J. E. Hale, N. Dai, and G. S. Worthen (2012) 47, 436-444
|Abstract »|Full Text »|PDF »
The E3 ubiquitin ligase MARCH8 negatively regulates IL-1{beta}-induced NF-{kappa}B activation by targeting the IL1RAP coreceptor for ubiquitination and degradation.
R. Chen, M. Li, Y. Zhang, Q. Zhou, and H.-B. Shu (2012)
PNAS
109, 14128-14133
|Abstract »|Full Text »|PDF »
Interleukin-1{beta} Promotes Proliferation and Inhibits Differentiation of Chondrocytes through a Mechanism Involving Down-Regulation of FGFR-3 and p21.
S. Simsa-Maziel and E. Monsonego-Ornan (2012)
Endocrinology
153, 2296-2310
|Abstract »|Full Text »|PDF »
Maximal Adjuvant Activity of Nasally Delivered IL-1{alpha} Requires Adjuvant-Responsive CD11c+ Cells and Does Not Correlate with Adjuvant-Induced In Vivo Cytokine Production.
A. L. Thompson, B. T. Johnson, G. D. Sempowski, M. D. Gunn, B. Hou, A. L. DeFranco, and H. F. Staats (2012)
J. Immunol.
188, 2834-2846
|Abstract »|Full Text »|PDF »
Interleukin-1{beta} (IL-1{beta}) promotes susceptibility of Toll-like receptor 5 (TLR5) deficient mice to colitis.
F. A. Carvalho, I. Nalbantoglu, S. Ortega-Fernandez, J. D. Aitken, Y. Su, O. Koren, W. A. Walters, R. Knight, R. E. Ley, M. Vijay-Kumar, et al. (2012)
Gut
61, 373-384
|Abstract »|Full Text »|PDF »
c-Jun N-terminal kinase phosphorylates DCP1a to control formation of P bodies.
K. Rzeczkowski, K. Beuerlein, H. Muller, O. Dittrich-Breiholz, H. Schneider, D. Kettner-Buhrow, H. Holtmann, and M. Kracht (2011)
J. Cell Biol.
194, 581-596
|Abstract »|Full Text »|PDF »
Serum Amyloid A Activates the NLRP3 Inflammasome and Promotes Th17 Allergic Asthma in Mice.
J. L. Ather, K. Ckless, R. Martin, K. L. Foley, B. T. Suratt, J. E. Boyson, K. A. Fitzgerald, R. A. Flavell, S. C. Eisenbarth, and M. E. Poynter (2011)
J. Immunol.
187, 64-73
|Abstract »|Full Text »|PDF »
Interleukin-1 in the pathogenesis and treatment of inflammatory diseases.
Neuropeptide Y Modulation of Interleukin-1{beta} (IL-1{beta})-induced Nitric Oxide Production in Microglia.
R. Ferreira, S. Xapelli, T. Santos, A. P. Silva, A. Cristovao, L. Cortes, and J. O. Malva (2010)
J. Biol. Chem.
285, 41921-41934
|Abstract »|Full Text »|PDF »
IL-1-induced Post-transcriptional Mechanisms Target Overlapping Translational Silencing and Destabilizing Elements in I{kappa}B{zeta} mRNA.
S. Dhamija, A. Doerrie, R. Winzen, O. Dittrich-Breiholz, A. Taghipour, N. Kuehne, M. Kracht, and H. Holtmann (2010)
J. Biol. Chem.
285, 29165-29178
|Abstract »|Full Text »|PDF »
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
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
