Murine microglial cells produce and respond to interleukin-18.
Interleukin (IL)-18 (interferon-gamma-inducing factor or IL-1gamma) belongs structurally to the IL-1 cytokine family and shares biological properties with IL-12. Expression, intracellular signaling, and functional relevance of IL-18 within the CNS are mostly unknown. We show that IL-18 protein is synthesized within mouse brain, preferentially during early postnatal stages, and that microglial cells but not astrocytes are a potential source. IL-18 is produced by cultured microglia on exposure to lipopolysaccharide (LPS). Microglia also express major components of the IL-1/IL-18 receptor system. On IL-18 stimulation, microglial IL-1 receptor-associated kinase (IRAK) can be coprecipitated with tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) but not with IL-1 receptor type I, indicating that IRAK recruits TRAF6 during IL-18 signaling. IL-18 inhibits the LPS-induced release of IL-12 and attenuates that of TNF-alpha, whereas the production of IL-6 and macrophage inflammatory protein-1alpha is only marginally affected. IL-18 may play a role during CNS development and can be produced by activated microglia, thus probably contributing to immune and inflammatory processes in the brain.
Prinz
M
M
Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Hanisch
U K
UK
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases; D020382:Interleukin-18 / Q000378:metabolism* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D048029:TNF Receptor-Associated Factor 6
D016207:Cytokines; D020382:Interleukin-18; D008070:Lipopolysaccharides; D011506:Proteins; D011994:Recombinant Proteins; D048029:TNF Receptor-Associated Factor 6; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases