Tumor necrosis factor-α enhances interferon-γ-mediated class II antigen expression on astrocytes

Etty N. Benveniste, Shaun M. Sparacio, John R. Bethea

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Astrocytes can function as antigen-presenting cells (APC) upon expression of class II antigens, which are induced by interferon-γ (IFN-γ). Tumor necrosis factor-α (TNF-α) can act synergistically with IFN-γ with respect to class II expression on a variety of cells. As brain cells themselves can secrete TNF-like factors upon stimulation, we examined the effect of TNF-α on IFN-γ-mediated class II induction on astrocytes. TNF-α alone had no effect on class II expression, but did synergize with IFN-γ for enhanced expression of class II antigens. The specificity of TNF-α activity was demonstrated by blocking the amplifying effect of TNF-α with a polyclonal anti-TNF-α antibody. Kinetic analysis of the synergistic effect indicated that optimal TNF-α enhancement of class II expression was observed when astrocytes were pretreated with IFN-γ 12-24 h prior to TNF-α addition. A possible mechanism for the synergistic action between IFN-γ and TNF-α may be increased TNF-α receptor expression by IFN-γ. Astrocytes treated with IFN-γ for 24 h express more TNF-α receptors (3900/cell) than do untreated astrocytes (2483/cell), with no significant change in the binding affinity (Kd). These results suggest that the synergistic activity of TNF-α requires an inductive signal from IFN-γ, which in part may be increased TNF-α receptor expression. Altogether, our observations indicate that TNF-α enhances ongoing class II major histocompatibility complex gene expression in rat astrocytes, which in this system is initially induced by IFN-γ. TNF-α exerts its effect by binding to high affinity TNF-α receptors on astrocytes, whose expression is also enhanced by IFN-γ. These two cytokines work in concert to elevate class II expression on astrocytes, an event which can contribute to initiation and/or perpetuation of intracerebral immune responses.

Original languageEnglish (US)
Pages (from-to)209-219
Number of pages11
JournalJournal of Neuroimmunology
Volume25
Issue number2-3
DOIs
StatePublished - Dec 1989

Keywords

  • Astrocyte
  • Interferon-γ
  • Major histocompatibility complex
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

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