Cytokine effects on glutamate uptake by human astrocytes

Shuxian Hu, Wen Sheng, Laura C. Ehrlich, Phillip K. Peterson, Chun C. Chao

Research output: Contribution to journalArticle

265 Scopus citations

Abstract

Glutamate uptake by astrocytes has been postulated to play a neuroprotective role during brain inflammation. Using primary human fetal astrocyte cultures, we investigated the influence of selected cytokines on glutamate uptake activity. Interleukin (IL)-1β and tumor necrosis factor-α dose-dependently inhibited astrocyte glutamate uptake, whereas interferon (IFN)-γ alone stimulated this activity. The nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine, blocked IL-1β-mediated inhibition of glutamate uptake, suggesting involvement of nitric oxide in the effect of IL-1β. IL-1 receptor antagonist protein totally reversed the inhibitory effect of cytokines, suggesting a critical role of IL-1β. The anti-inflammatory cytokine IFN-β blocked cytokine (IL-1β plus IFN-γ)-induced inhibition of glutamate uptake with a corresponding reduction in nitric oxide generation. Taken together, these findings suggest that proinflammatory cytokines inhibit astrocyte glutamate uptake by a mechanism involving nitric oxide, and that IFN-β may exert a therapeutically beneficial effect by blocking cytokine- induced nitric oxide production in inflammatory diseases of the brain. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalNeuroImmunoModulation
Volume7
Issue number3
DOIs
StatePublished - Apr 2000

Keywords

  • Astrocytes
  • Cytokines
  • Glutamate uptake
  • Interferon
  • Interleukin-1
  • Nitric oxide

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