title: Contribution of interleukin-1 receptor accessory protein B to interleukin-1 actions in neuronal cells.
abstract: Interleukin (IL)-1 is an important neuroimmunomodulator and a key mediator of inflammation during brain disorders. It acts on neuronal and glial cells via binding to the IL-1 type 1 receptor and IL-1 receptor accessory protein (IL-1RAcP). More recently, a neuronal-specific isoform of IL-1RAcP, named IL-1RAcPb, has been identified. Our aim was to determine the role of IL-1RAcPb in IL-1 actions in neuronal and glial cells, and to further explore the signaling mechanisms of IL-1 in neurons. We found that IL-1RAcPb deletion had no effect on IL-1α- and IL-1β-induced activation of the extracellular signal-regulated kinase 1/2 or IL-6 release in glial cultures, although IL-6 release in response to high IL-1α concentration (30 IU/ml) was significantly reduced. We identified the p38 kinase as a key signaling element in IL-1α- and IL-1β-induced IL-6 synthesis and release in neuronal cultures. IL-1RAcPb deletion had no effect on IL-1α- and IL-1β-induced IL-6 release in neurons, but significantly reduced IL-1α- but not IL-1β-induced p38 phosphorylation. Our data demonstrate that the p38 signaling pathway plays an important role in IL-1 actions in neurons, and that IL-1RAcP may regulate some, but not all, neuronal activities in response to IL-1α.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: L
authors.initials: L
authors.lastname: Nguyen
authors.forename: N J
authors.initials: NJ
authors.lastname: Rothwell
authors.forename: E
authors.initials: E
authors.lastname: Pinteaux
authors.forename: H
authors.initials: H
authors.lastname: Boutin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053577:Interleukin-1 Receptor Accessory Protein / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000378:metabolism*
chemical_list: D053577:Interleukin-1 Receptor Accessory Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D017472:Receptors, Interleukin-1