TY - JOUR
T1 - Interleukin-1β induction of tumor necrosis factor-alpha gene expression in human astroglioma cells
AU - Bethea, John R.
AU - Il Yup, Chung
AU - Sparacio, Shaun M.
AU - Yancey Gillespie, G.
AU - Benveniste, Etty N.
N1 - Funding Information:
This work was supported in part by grants RG 2205-A-3 and RG 2269-A-4 from the National Multiple Sclerosis Society (E.N.B), grant AI 27290 from the National Institutes of Health (E.N.B.), grants CA 51857 and NS 20023 from the National Institutes of Health (G.Y.G.) and a grant from the Preuss Foundation for Brain Tumor Research (G.Y.G.). J.R.B. is affiliated with the Graduate Training Program in Neuroscience.
PY - 1992/2
Y1 - 1992/2
N2 - 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.
AB - 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.
KW - Astrocyte
KW - Central nervous system
KW - Cytokine
UR - http://www.scopus.com/inward/record.url?scp=0026602243&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026602243&partnerID=8YFLogxK
U2 - 10.1016/0165-5728(92)90049-Q
DO - 10.1016/0165-5728(92)90049-Q
M3 - Article
C2 - 1732280
AN - SCOPUS:0026602243
VL - 36
SP - 179
EP - 191
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
SN - 0165-5728
IS - 2-3
ER -