Interleukin-1β induction of TNF-α gene expression: Involvement of protein kinase C

John R. Bethea, G. Yancey Gillespie, Etty N. Benveniste

Research output: Contribution to journalArticle

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Abstract

In the human astroglioma cell line CH235-MG, interleukin-1β (IL-1β) induces transcriptional activation of the tumor necrosis factor-alpha (TNF-α) gene, resulting in expression of TNF-α mRNA and biologically active TNF-α protein. This study was undertaken to elucidate intracellular signaling pathways involved in IL-1β induction of the TNF-α gene. We demonstrated that the protein kinase C (PKC) activator 4β-phorhol 12β-myristate 13α-acetate (PMA) in concert with Ca++ ionophore A23187 induced expression of TNF-α mRNA and protein, whereas an inactive PMA analogue (αPMA) had no effect. Various cyclic nucleotide activators such as 8-Bromo cAMP, cholera toxin, and forskolin had no effect on TNF-α production. Two PKC inhibitors, H7 and staurosporine (SS), abrogated IL-1β induced TNF-α expression in a dose-dependent fashion. Treatment of CH235-MG cells with a high concentration of PMA (1 μM) for an extended period of time (48 h) caused a greater than 90% reduction in total PKC activity. Further strengthening a role for PKC in this cytokine response is the fact that IL-1β was no longer able to induce TNF-α expression in these PKC depleted cells. Last, IL-1β treatment produced an increase of total PKC activity in CH235-MG cells. Taken together, these data demonstrate that IL-1β induces TNF-α gene expression in CH235-MG cells in a PKC-dependent manner.

Original languageEnglish
Pages (from-to)264-273
Number of pages10
JournalJournal of Cellular Physiology
Volume152
Issue number2
StatePublished - Aug 1 1992

Fingerprint

Interleukin-1
Gene expression
Protein Kinase C
Tumor Necrosis Factor-alpha
Gene Expression
Myristic Acid
Acetates
Genes
8-Bromo Cyclic Adenosine Monophosphate
Messenger RNA
Staurosporine
Protein C Inhibitor
Cholera Toxin
Cyclic Nucleotides
Ionophores
Astrocytoma
Calcimycin
Colforsin
Protein Kinase Inhibitors
Transcriptional Activation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Bethea, J. R., Gillespie, G. Y., & Benveniste, E. N. (1992). Interleukin-1β induction of TNF-α gene expression: Involvement of protein kinase C. Journal of Cellular Physiology, 152(2), 264-273.

Interleukin-1β induction of TNF-α gene expression : Involvement of protein kinase C. / Bethea, John R.; Gillespie, G. Yancey; Benveniste, Etty N.

In: Journal of Cellular Physiology, Vol. 152, No. 2, 01.08.1992, p. 264-273.

Research output: Contribution to journalArticle

Bethea, JR, Gillespie, GY & Benveniste, EN 1992, 'Interleukin-1β induction of TNF-α gene expression: Involvement of protein kinase C', Journal of Cellular Physiology, vol. 152, no. 2, pp. 264-273.
Bethea, John R. ; Gillespie, G. Yancey ; Benveniste, Etty N. / Interleukin-1β induction of TNF-α gene expression : Involvement of protein kinase C. In: Journal of Cellular Physiology. 1992 ; Vol. 152, No. 2. pp. 264-273.
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