title: Interleukin-18 induces expression and release of cytokines from murine glial cells: interactions with interleukin-1 beta.
abstract: Interleukin (IL)-18, a member of the IL-1 cytokine family, is an important mediator of peripheral inflammation and host defence responses. IL-1 is a key proinflammatory cytokine in the brain, but the role of IL-18 in the CNS is not yet clear. The objective of this study was to investigate the actions of IL-18 on mouse glial cells. IL-18 induced intracellular expression of IL-1 alpha and proIL-1 beta, and release of IL-6 from mixed glia. Treatment of lipopolysaccharide-primed microglia with adenosine triphosphate (ATP), an endogenous secondary stimulus, induced IL-1 beta and IL-18 release. Although deletion of the IL-18 gene did not affect IL-1 beta expression or release in this experimental paradigm, IL-1 beta knockout microglia released significantly less IL-18 compared to wild-type microglia. In addition, ATP induced release of mature IL-1 beta from IL-18-primed microglia. These data suggest that IL-18 may contribute to inflammatory responses in the brain, and demonstrate that, in spite of several common features, IL-18 and IL-1 beta differ in their regulation and actions.
authors.affiliation: School of Biological Sciences, University of Manchester, Oxford Road, Manchester, UK. rachel.wheeler@mail.mcgill.ca
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Wheeler
authors.forename: David
authors.initials: D
authors.lastname: Brough
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Le Feuvre
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Giamal N
authors.initials: GN
authors.lastname: Luheshi
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rothwell
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D053727:Interleukin-18 Receptor alpha Subunit; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053724:Receptors, Interleukin-18
chemical_list: D016207:Cytokines; C508573:Il18r1 protein, mouse; D007375:Interleukin-1; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D008070:Lipopolysaccharides; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D000255:Adenosine Triphosphate