Microglia and macrophages express tumor necrosis factor receptor p75 following middle cerebral artery occlusion in mice

Kate Lykke Lambertsen, Bettina Hjelm Clausen, Claus Fenger, Helle Wulf Johansson, Trevor Owens, Frederik Dagnaes-Hansen, Michael Meldgaard, Bente Finsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The proinflammatory and potential neurotoxic cytokine tumor necrosis factor (TNF) is produced by activated CNS resident microglia and infiltrating blood-borne macrophages in infarct and peri-infarct areas following induction of focal cerebral ischemia. Here, we investigated the expression of the TNF receptors, TNF-p55R and TNF-p75R, from 1 to 10 days following permanent occlusion of the middle cerebral artery in mice. Using quantitative polymerase chain reaction (PCR), we observed that the relative level of TNF-p55R mRNA was significantly increased at 1-2 days and TNF-p75R mRNA was significantly increased at 1-10 days following arterial occlusion, reaching peak values at 5 days, when microglial-macrophage CD11b mRNA expression was also increased. In comparison, the relative level of TNF mRNA was significantly increased from 1 to 5 days, with peak levels 1 day after arterial occlusion. In situ hybridization revealed mRNA expression of both receptors in predominantly microglial- and macrophage-like cells in the peri-infarct and subsequently in the infarct, and being most marked from 1 to 5 days. Using green fluorescent protein-bone marrow chimeric mice, we confirmed that TNF-p75R was expressed in resident microglia and blood-borne macrophages located in the peri-infarct and infarct 1 and 5 days after arterial occlusion, which was supported by Western blotting. The data show that increased expression of the TNF-p75 receptor following induction of focal cerebral ischemia in mice can be attributed to expression in activated microglial cells and blood-borne macrophages.
Original languageEnglish
JournalNeuroscience
Volume144
Issue number3
Pages (from-to)934-49
Number of pages15
ISSN0306-4522
DOIs
Publication statusPublished - 9. Feb 2007

Keywords

  • Animals
  • Antigens, CD11
  • Brain
  • Brain Infarction
  • Cytokines
  • Gliosis
  • Green Fluorescent Proteins
  • Infarction, Middle Cerebral Artery
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia
  • Middle Cerebral Artery
  • RNA, Messenger
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Signal Transduction
  • Transplantation Chimera
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha
  • Up-Regulation

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