IL‐1F5 mediates anti‐inflammatory activity in the brain through induction of IL‐4 following interaction with SIGIRR/TIR8
- 18 February 2008
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 105 (5), 1960-1969
- https://doi.org/10.1111/j.1471-4159.2008.05304.x
Abstract
Similarity in structure and sequence homology has led to the identification of new members of the interleukin-1 (IL-1) ligand and receptor superfamilies. IL-1F6, IL-1F8 and IL-1F9 have been shown to signal through IL-1R-related protein 2 and IL-1 receptor accessory protein leading to activation of NFkappaB, while IL-1F7 and IL-1F10 interact with the IL-18 receptor and the soluble IL-1 receptor type I respectively. In contrast, identification of a biological role for IL-1F5 has remained elusive, with conflicting data relating to its possible ability to antagonize IL-1F9-stimulated activation of NFkappaB in Jurkat cells transfected with IL-1R-related protein 2. In this study, we set out to investigate a possible role for IL-1F5 in the brain and report that it antagonizes the inflammatory effects of IL-1beta and lipopolysaccharide (LPS) in vivo and in vitro including the inhibitory effect on long-term potentiation (LTP) in rat hippocampus. We demonstrate that IL-1F5 induces IL-4 mRNA and protein expression in glia in vitro and enhances hippocampal expression of IL-4 following intracerebroventricular (i.c.v.) injection. The inhibitory effect of IL-1F5 on LPS-induced IL-1beta is attenuated in cells from IL-4-defective (IL-4-/- mice). Our findings suggest that IL-1F5 mediates anti-inflammatory effects through its ability to induce IL-4 production and that this is a consequence of its interaction with the orphan receptor, single Ig IL-1R-related molecule (SIGIRR)/TIR8, as the effects were not observed in SIGIRR-/- mice. In contrast to its effects in brain tissue, IL-1F5 did not attenuate LPS-induced changes, or up-regulated IL-4 in macrophages or dendritic cells, suggesting that the effect is confined to the brain.Keywords
This publication has 40 references indexed in Scilit:
- A novel alternatively spliced interleukin-1 receptor accessory protein mIL-1RAcP687Molecular Immunology, 2007
- Interleukin-6 Facilitates Lipopolysaccharide-Induced Disruption in Working Memory and Expression of Other Proinflammatory Cytokines in Hippocampal Neuronal Cell LayersJournal of Neuroscience, 2006
- The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-β1–42 in the rat hippocampus in vivoNeuropharmacology, 2006
- Regulation of expression of the novel IL‐1 receptor family members in the mouse brainJournal of Neurochemistry, 2005
- SIGIRR Inhibits Interleukin-1 Receptor- and Toll-like Receptor 4-mediated Signaling through Different MechanismsJournal of Biological Chemistry, 2005
- Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-β-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neuronsHippocampus, 2005
- Neuroprotective actions of eicosapentaenoic acid on lipopolysaccharide‐induced dysfunction in rat hippocampusJournal of Neurochemistry, 2004
- Interleukin-1 homologues IL-1F7b and IL-18 contain functional mRNA instability elements within the coding region responsive to lipopolysaccharideBiochemical Journal, 2004
- Apoptotic Changes in the Aged Brain Are Triggered by Interleukin-1β-induced Activation of p38 and Reversed by Treatment with Eicosapentaenoic AcidPublished by Elsevier BV ,2002
- Interleukin 1 ? markedly stimulates nitric oxide formation in the absence of other cytokines or lipopolysaccharide in primary cultured rat hepatocytes but not in Kupffer cellsHepatology, 1996