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Murine Microglial Cells Produce and Respond to Interleukin‐18
Author(s) -
Prinz Marco,
Hanisch UweKarsten
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722215.x
Subject(s) - microglia , interleukin 1β , neuroscience , interleukin , microbiology and biotechnology , biology , immunology , chemistry , cytokine , inflammation
Interleukin (IL)‐18 (interferon‐δ‐inducing factor or IL‐1δ) 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‐α, whereas the production of IL‐6 and macrophage inflammatory protein‐1 a 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.