Substance P induces secretion of immunomodulatory cytokines by human astrocytoma cells.
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.
Palma
C
C
Department of Pharmacology, Menarini Ricerche, Pomezia, Rome, Italy.
Manzini
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S
D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004151:Dipeptides; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007211:Indoles; D015850:Interleukin-6; D016209:Interleukin-8; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D009363:Neoplasm Proteins; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018040:Receptors, Neurokinin-1; C078949:FK 888; D013373:Substance P; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate