Interleukin-1 beta induction of tumor necrosis factor-alpha gene expression in human astroglioma cells.
Journal: 1992/February - Journal of Neuroimmunology
ISSN: 0165-5728
PUBMED: 1732280
Abstract:
Cells that produce tumor necrosis factor-alpha (TNF-alpha) 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-alpha; 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-1 beta (IL-1 beta) on the expression of TNF-alpha by CH235-MG human malignant glioma cells. CH235-MG cells do not constitutively express TNF-alpha mRNA or protein; however, upon stimulation with IL-1 beta, these cells synthesize and secrete biologically active TNF-alpha. IL-1 beta induces the expression of a 1.9 kb TNF-alpha mRNA species. Kinetic analysis demonstrated optimum TNF-alpha mRNA expression after a 4 h exposure to IL-1 beta, and peak TNF-alpha protein production at 18 h. Cycloheximide (CHX), an inhibitor of protein synthesis, markedly increased expression of TNF-alpha mRNA in IL-1 beta stimulated CH235-MG cells, indicating that de novo protein synthesis is not required for astroglioma TNF-alpha gene expression. Nuclear run-off analysis demonstrates that IL-1 beta causes transcriptional activation of the TNF-alpha gene, and CHX enhances IL-1 beta-induced TNF-alpha transcription. Studies of TNF-alpha mRNA stability using actinomycin D show that IL-1 beta-induced TNF-alpha mRNA has a half-life of approximately 30 min, and CHX increases the half-life of IL-1 beta-induced TNF-alpha mRNA to approximately 210 min. These results indicate that IL-1 beta, a cytokine present in the central nervous system during some pathological disease states, is a potent inducer of TNF-alpha in human malignant glioma cells.
Relations:
Citations
(9)
Grants
(311)
Diseases
(1)
Chemicals
(4)
Organisms
(1)
Processes
(3)
Anatomy
(1)
Similar articles
Articles by the same authors
Discussion board
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.