title: Expression of interleukin-1 receptors and their role in interleukin-1 actions in murine microglial cells.
abstract: Interleukin (IL)-1 is an important mediator of acute brain injury and inflammation, and has been implicated in chronic neurodegeneration. The main source of IL-1 in the CNS is microglial cells, which have also been suggested as targets for its action. However, no data exist demonstrating expression of IL-1 receptors [IL-1 type-I receptor (IL-1RI), IL-1 type-II receptor (IL-1RII) and IL-1 receptor accessory protein (IL-1RAcP)] on microglia. In the present study we investigated whether microglia express IL-1 receptors and whether they present target or modulatory properties for IL-1 actions. RT-PCR analysis demonstrated lower expression of IL-1RI and higher expression of IL-1RII mRNAs in mouse microglial cultures compared with mixed glial or pure astrocyte cultures. Bacterial lipopolysaccharide (LPS) caused increased expression of IL-1RI, IL-1RII and IL-1RAcP mRNAs, induced the release of IL-1beta, IL-6 and prostaglandin-E2 (PGE2), and activated nuclear factor kappaB (NF-kappaB) and the mitogen-activated protein kinases (MAPKs) p38, and extracellular signal-regulated protein kinase (ERK1/2), but not c-Jun N-terminal kinase (JNK) in microglial cultures. In comparison, IL-1beta induced the release of PGE2, IL-6 and activated NF-kappaB, p38, JNK and ERK1/2 in mixed glial cultures, but failed to induce any of these responses in microglial cell cultures. IL-1beta also failed to affect LPS-primed microglial cells. Interestingly, a neutralizing antibody to IL-1RII significantly increased the concentration of IL-1beta in the medium of LPS-treated microglia and exacerbated the IL-1beta-induced IL-6 release in mixed glia, providing the first evidence that microglial IL-1RII regulates IL-1beta actions by binding excess levels of this cytokine during brain inflammation.
authors.affiliation: School of Biological Sciences, University of Manchester, Manchester, UK. emmanuel.pinteaux@man.ac.uk
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Pinteaux
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Parker
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: Giamal N
authors.initials: GN
authors.lastname: Luheshi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D053577:Interleukin-1 Receptor Accessory Protein; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis*; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II
chemical_list: D017077:Culture Media, Conditioned; C507767:Il1rap protein, mouse; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011506:Proteins; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D015232:Dinoprostone