TY - JOUR
T1 - IL-1F5 mediates anti-inflammatory activity in the brain through induction of IL-4 following interaction with SIGIRR/TIR8
AU - Costelloe, Ceire
AU - Watson, Melanie
AU - Murphy, Aine
AU - McQuillan, Keith
AU - Loscher, Christine
AU - Armstrong, Michelle E.
AU - Garlanda, Cecilia
AU - Mantovani, Alberto
AU - O'Neill, Luke A J
AU - Mills, Kingston H G
AU - Lynch, Marina A.
PY - 2008/6
Y1 - 2008/6
N2 - 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 NFκB, 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 NFκB 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-1β 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-1β 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.
AB - 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 NFκB, 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 NFκB 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-1β 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-1β 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.
KW - Cytokine
KW - Cytokine receptor
KW - Interleukin-1β
KW - Interleukin-4
KW - Single Ig IL-1 receptor-related molecule
UR - http://www.scopus.com/inward/record.url?scp=43549123287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43549123287&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2008.05304.x
DO - 10.1111/j.1471-4159.2008.05304.x
M3 - Article
C2 - 18284608
AN - SCOPUS:43549123287
VL - 105
SP - 1960
EP - 1969
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -