title: Regulation of expression of the novel IL-1 receptor family members in the mouse brain.
abstract: Members of the interleukin-1 (IL-1) family of cytokines are key mediators in the regulation of host defence responses and the development of inflammation in response to acute and chronic injury to the brain. Two major agonists, IL-1alpha and IL-1beta, bind to a membrane receptor complex composed of the type-1 IL-1 receptor (IL-1RI) and the accessory protein (IL-1RAcP). The discovery of new orphan members of the IL-1 receptor superfamily (including ST2/T1, IL-1Rrp2, TIGIRR1 and -2, SIGGIR, IL-18Ralpha and IL-18Rbeta) has increased speculation that alternative IL-1 ligands signalling pathways exist in the brain. We demonstrate here that all the IL-1R-like orphan receptors are expressed by many brain cell types including astrocytes, microglia, oligodendrocytic progenitor cells and neurons. IL-18Rbeta expression was significantly increased in response to treatment of mixed glia with bacterial lipopolysaccharide (LPS) in vitro, whereas expression of IL-1Rrp2 and TIGIRR1 was reduced. Furthermore, IL-18Rbeta, IL-1Rrp2, but not TIGIRR1 expression, was increased in the brain in vivo in response to peripheral administration of LPS or middle cerebral artery occlusion (MCA). These results suggest possible roles for newly identified members of the IL-1 receptor family in CNS diseases.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Ralph
authors.initials: R
authors.lastname: Andre
authors.forename: Dominique
authors.initials: D
authors.lastname: Lerouet
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinteaux
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rothwell
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1