Interleukin-6 production by U373 MG, a human astrocytoma cell line: different pathways involved in substance P and lipopolysaccharide activation.
Substance P (SP) and lipopolysaccharide (LPS) stimulated interleukin-6 (IL-6) gene expression, as well as IL-6 protein secretion in the human astrocytoma cell line U373 MG. Staurosporine, an inhibitor of protein kinase C (PKC), entirely blocked SP- but not LPS-induced IL-6 release. In addition, the down regulation of PKC inhibited the SP response and only marginally altered LPS activation. Differently from SP, LPS-induced IL-6 release was markedly reduced by W7, a calmodulin antagonist. Moreover, SP interacted in a synergistic manner with LPS. Thus, neural (SP) and bacterial (LPS) mediators stimulate U373 MG IL-6 release via distinct, though not antagonistic, activation pathways.
Palma
C
C
Department of Pharmacology, Menarini Ricerche Sud, Pomezia, Rome, Italy.
Urbani
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F
Manzini
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S
D000470:Alkaloids / Q000494:pharmacology; D001254:Astrocytoma / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects; D019311:Staurosporine; D013373:Substance P / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018040:Receptors, Neurokinin-1; D013449:Sulfonamides; D013373:Substance P; D000001:Calcimycin; D003994:Bucladesine; C017967:W 7; D002772:Cholera Toxin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin