Abstract
Pretreatment of LPS-induced RAW 264.7 cells with three PKC inhibitors suggests that induction of TNF-alpha, nitric oxide (NO), gelatinase B (Gel B) and IL-6 involves at least three distinct signalling pathways. We confirmed the PKC dependence of TNF-alpha and NO productions and found that Gel B was inhibited by Calphostin C (CAL), but potentiated by staurosporine (STAR) and CGP 41 251. IL-6 production was stimulated by the three inhibitors. Our results indicate that up-regulation of Gel B, TNF-alpha and NO seems to involve PKC at different levels, whereas up-regulation of IL-6 production appears to be PKC-independent. However, IL-6 production in RAW 264.7 cells seems to be down-regulated by a PKC-dependent feedback mechanism.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / pharmacology*
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Animals
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Biological Assay
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Blotting, Northern
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Cell Line, Transformed
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Collagenases / analysis
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Collagenases / biosynthesis*
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Gene Expression / drug effects*
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Interleukin-6 / analysis
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Interleukin-6 / biosynthesis*
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Macrophages / drug effects
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Macrophages / immunology*
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Macrophages / metabolism
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Matrix Metalloproteinase 9
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Mice
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Naphthalenes*
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Nitric Oxide / biosynthesis
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Polycyclic Compounds / pharmacology*
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Protein Kinase C / antagonists & inhibitors*
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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Staurosporine
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Alkaloids
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Interleukin-6
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Naphthalenes
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Polycyclic Compounds
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Nitric Oxide
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Protein Kinase C
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Collagenases
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Matrix Metalloproteinase 9
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Staurosporine
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calphostin C
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midostaurin