Interleukin-1β induction of tumor necrosis factor-alpha gene expression in human astroglioma cells

John R. Bethea, Chung Il Yup, Shaun M. Sparacio, G. Yancey Gillespie, Etty N. Benveniste

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

Cells that produce tumor necrosis factor-α (TNF-α) require the presence of signaling molecules since this cytokine is not normally expressed in a constitutive manner. It has been demonstrated that glial cells can produce TNF-α; however, the specific inducing molecules and their mechanism(s) of action have not been clearly defined. In this study, we examined the effect of human recombinant interleukin-1β (IL-1β) on the expression of TNF-α by CH235-MG human malignant glioma cells. CH235-MG cells do not constitutively express TNF-α mRNA or protein; however, upon stimulation with IL-1β, these cells synthesize and secrete biologically active TNF-α. IL-1β induces the expression of a 1.9 kb TNF-α mRNA species. Kinetic analysis demonstrated optimum TNF-α mRNA expression after a 4 h exposure to IL-1β, and peak TNF-α protein production at 18 h. Cycloheximide (CHX), an inhibitor of protein synthesis, markedly increases expression of TNF-α mRNA in IL-1β stimulated CH235-MG cells, indicating that de novo protein synthesis is not required for astroglioma TNF-α gene expression. Nuclear run-off analysis demonstrates that IL-1β causes transcriptional activation of the TNF-α gene, and CHX enhances, IL-1β-induced TNF-α transcription. Studies of TNF-α mRNA stability using actinomycin D show that IL-1β-induced TNF-α mRNA has a half-life of approximately 30 min, and CHX increases the half-life of IL-1β-induced TNF-α mRNA to approximately 210 min. These results indicate that IL-1β, a cytokine present in the central nervous system during some pathological disease states, is a potent inducer of TNF-α in human malignant glioma cells.

Original languageEnglish (US)
Pages (from-to)179-191
Number of pages13
JournalJournal of Neuroimmunology
Volume36
Issue number2-3
DOIs
StatePublished - Feb 1992

Keywords

  • Astrocyte
  • Central nervous system
  • Cytokine

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

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    Bethea, J. R., Il Yup, C., Sparacio, S. M., Yancey Gillespie, G., & Benveniste, E. N. (1992). Interleukin-1β induction of tumor necrosis factor-alpha gene expression in human astroglioma cells. Journal of Neuroimmunology, 36(2-3), 179-191. https://doi.org/10.1016/0165-5728(92)90049-Q