Abstract
In human astrocytoma cell lines, substance P (SP) stimulated interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor and leukemia inhibitory factor protein secretion. These SP effects were blocked by a specific NK1 tachykinin receptor antagonist. Further, SP stimulation increased the half-life of IL-6 and IL-8 messenger RNAs, suggesting that the synthesis of these cytokines is also regulated post-transcriptionally. SP-induced cytokine release was inhibited by staurosporine and phorbol 12-myristate 13-acetate desensitization suggesting protein kinase C involvement. The demonstration that SP affects cytokine production in glioma cells might be of relevance for the biology of such tumors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Astrocytoma / genetics
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Astrocytoma / metabolism
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Astrocytoma / pathology*
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology*
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Cytokines / metabolism*
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Dipeptides / pharmacology
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Neoplastic / drug effects
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Growth Inhibitors / metabolism
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Humans
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Indoles / pharmacology
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Interleukin-6 / biosynthesis
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Interleukin-8 / biosynthesis
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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Leukemia Inhibitory Factor
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Lymphokines / metabolism
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / physiology*
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Neurokinin-1 Receptor Antagonists
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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RNA, Messenger / metabolism
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RNA, Neoplasm / metabolism
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Receptors, Neurokinin-1 / physiology*
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Staurosporine / pharmacology
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Substance P / pharmacology*
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
Substances
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Cytokines
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Dipeptides
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Enzyme Inhibitors
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Growth Inhibitors
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Indoles
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Interleukin-6
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Interleukin-8
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LIF protein, human
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Leukemia Inhibitory Factor
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Lymphokines
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Neoplasm Proteins
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Neurokinin-1 Receptor Antagonists
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RNA, Messenger
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RNA, Neoplasm
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Receptors, Neurokinin-1
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FK 888
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Substance P
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Granulocyte-Macrophage Colony-Stimulating Factor
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Protein Kinase C
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Staurosporine
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Tetradecanoylphorbol Acetate