Modulation of human microglial cell superoxide production by cytokines

C. C. Chao, S. Hu, P. K. Peterson

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Reactive oxygen intermediates (e,g., superoxide [O2-]) generated by microglia may play a role in host defense and injury within the central nervous system. We investigated the effect of cytokines on human microglial cell O2- production on stimulation with phorbol myristate acetate. Priming of microglial cell cultures with interferon-γ or tumor necrosis factor-a resulted in a dose- and time-dependent enhancement of O2- production. The priming effects of these cytokines were mediated through a protein kinase C signal transduction pathway. In contrast, astrocytes did not generate detectable O2- on phorbol myristate acetate stimulation. Treatment of microglia with transforming growth factor-β, interleukin-4, or interleukin -10 suppressed in a dose-dependent manner the priming effects of tumor necrosis factor-α and interferon-γ. The results of this study have implications for understanding the mechanisms by which cytokines and microglia contribute to processes of host defense and neurodegeneration via generation of reactive oxygen intermediates.

Original languageEnglish (US)
Pages (from-to)65-70
Number of pages6
JournalJournal of Leukocyte Biology
Volume58
Issue number1
DOIs
StatePublished - Jan 1 1995

Keywords

  • Interferon-γ
  • Interleukin-10
  • Interleukin-4
  • Microglia
  • Transforming growth factor-β
  • Tumor necrosis factor-α

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