Neuronal injury induces cytokine-induced neutrophil chemoattractant-1 (CINC-1) production in astrocytes

Takahiro Katayama, Hiroki Tanaka, Tadashi Yoshida, Takashi Uehara, Masabumi Minami

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Accumulating evidence indicates a pivotal role for neuroinflammation in ischemic and excitotoxic brain injury. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) is a CXC chemokine implicated in the infiltration of inflammatory cells into the brain parenchyma. In this study, we investigated the effect of N-methyl-D-aspartate (NMDA)-induced neuronal injury on CINC-1 production in the organotypic cortico-striatal slice cultures. Treatment with 50 μM NMDA for 3-4h caused devastating neuronal damage and increased CINC-1 production. Immunohistochemical analysis revealed that the CINC-1 immunoreactivity was predominantly detected in astrocytes. NMDA failed to induce CINC-1 production in enriched astrocyte cultures or neuron-depleted slice cultures, suggesting that NMDA acted on neuronal cells to induce astrocytic CINC-1 production. NMDA-induced CINC-1 mRNA expression was significantly inhibited by U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor. These results suggest that NMDA-evoked neuronal injury induced astrocytic CINC-1 production via a MEK/ERK signaling pathway. Manipulation of this signaling pathway may serve as a target for suppressing neuroinflammation and, thereby, treating ischemic brain injury.

Original languageEnglish
Pages (from-to)88-93
Number of pages6
JournalJournal of Pharmacological Sciences
Volume109
Issue number1
DOIs
Publication statusPublished - Jan 29 2009
Externally publishedYes

Keywords

  • Astrocyte
  • Chemokine
  • Mitogen-activated protein (MAP) kinase
  • N-methyl-D-aspartate (nmda)
  • Organotypic slice culture

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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