IL-1Rrp2 expression and IL-1F9 (IL-1H1) actions in brain cells

Elisabet Berglöf, Ralph Andre, Blair R. Renshaw, Stuart M. Allan, Catherine B. Lawrence, Nancy J. Rothwell, Emmanuel Pinteaux

Research output: Contribution to journalArticlepeer-review

Abstract

The recently discovered IL-1F9 (IL-1H1) is a putative member of the interleukin (IL)-1 family of cytokines that has been shown to activate nuclear factor-kappa B (NFκB) in Jurkat cells transfected with the orphan receptor IL-1 receptor-related protein (IL-1Rrp)2. The aim of the present study was therefore to investigate expression of IL-1Rrp2 and to determine if IL-1F9 induces known IL-1 signaling pathways in the different cell types of the mouse brain in culture. Messenger RNA for IL-1Rrp2 was not detected in primary neurones by RT-PCR, but significant constitutive expression was found in mixed glial cells, particularly in astrocytes and microglia, which was strongly decreased by exposure to bacterial lipopolysaccharide (LPS). LPS induced the release of IL-6, and activated NFκB and the mitogen-activated protein kinases (MAPKs) p38, extracellular signal-regulated protein kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) in microglial cultures. IL-1β induced release of IL-6 and activated NFκB, p38, JNK and ERK1/2 in mixed glial cultures, which was completely abolished in the presence of IL-1 receptor antagonist (IL-1ra). When injected intracerebroventrically in the rat, IL-1β increased core body temperature, and reduced body weight and food intake. In contrast, IL-1F9 failed to induce any of these responses either in vivo or in vitro. These results demonstrate that glial cells may be a target for the new ligand IL-1F9, since high expression of IL-1Rrp2 mRNA was detected in these cells. However, IL-1F9 failed to induce any of the classical IL-1β responses, suggesting that it may trigger alternative pathway(s). © 2003 Elsevier Science B.V. All rights reserved.
Original languageEnglish
Pages (from-to)36-43
Number of pages7
JournalJournal of neuroimmunology
Volume139
Issue number1-2
DOIs
Publication statusPublished - Jun 2003

Keywords

  • CNS
  • IL-1F
  • Interleukin-1
  • New ligands
  • Novel receptor
  • Signaling

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