Abstract
Recent studies have shown that somatostatin (SOM) inhibits interleukin 6 (IL-6) and interferon gamma (IFNgamma) production by lymphocytes and peritoneal macrophages, whereas substance P (SP) enhances these cytokines production. To define the mechanism of the cytokine production enhancements and inhibitions by SOM and SP, we examined the expression of apoptosis modulator, p53, Bcl-2, Bax, inducible nitric oxide synthase (iNOS), Fas, caspase-8 and nitric oxide (NO) in thioglycolate-elicited peritoneal macrophages. SOM caused up-regulation of p53, Bcl-2, Fas and caspase-8 activities, and down-regulation of iNOS expression and NO production. On the other hand, SP slightly induces p53 and highly induces Bcl-2, iNOS expression and NO production. These data suggest that apoptosis by SOM may occur by a Bax- and NO-independent p53 accumulation, and through Fas and caspase-8 activation pathways, and that the inducible expression of Bcl-2 and NO production by SP may contribute to prevent the signals of apoptosis by Bax, and via Fas and caspase-8 activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects*
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Blotting, Western
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Caspase 8
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Caspase 9
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Caspases / biosynthesis
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Cell Nucleus / ultrastructure
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Cells, Cultured
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DNA Fragmentation / drug effects
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Down-Regulation
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Macrophage Activation / drug effects
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / immunology*
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Macrophages, Peritoneal / ultrastructure
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Mice
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Mice, Inbred C3H
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Somatostatin / pharmacology*
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Substance P / pharmacology*
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Tumor Suppressor Protein p53 / biosynthesis
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Up-Regulation
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bcl-2-Associated X Protein
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fas Receptor / biosynthesis
Substances
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Bax protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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fas Receptor
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Nitric Oxide
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Substance P
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Somatostatin
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Casp8 protein, mouse
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Casp9 protein, mouse
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Caspase 8
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Caspase 9
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Caspases