Abstract
In this study, we demonstrated evidence for the induction of CD80+ monocytes by staphylococcal enterotoxin B (SEB) via caspase actions. Pre-treatment with pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappaB, resulted in a significant reduction in the percentage of SEB- and interferon-gamma (IFN-gamma) (produced by SEB) -induced CD80+ monocytes. SEB and IFN-gamma activated NF-kappaB, which was inhibited by PDTC. SEB induced the activation of caspase-3 and -8, and pre-treatment with z-VAD-fmk, a broad-spectrum inhibitor of caspases, prevented the induction of apoptosis. Treating with z-VAD-fmk resulted in a reduction of the generation of CD80+ monocytes. These results indicated that CD80 driven by NF-kappaB is regulated by the enzymatic actions of caspases, which allows monocytes to participate in massive T-cell activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Amino Acid Chloromethyl Ketones / pharmacology
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Antibodies, Monoclonal / chemistry
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Apoptosis
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B7-1 Antigen / biosynthesis*
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B7-1 Antigen / chemistry
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Caspase 3
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Caspase 8
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Caspases / metabolism
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Caspases / physiology*
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Cells, Cultured
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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Enterotoxins / metabolism
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Enzyme Activation
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Humans
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Interferon-gamma / metabolism
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Leukocytes, Mononuclear / metabolism
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Middle Aged
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Monocytes / metabolism*
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NF-kappa B / metabolism
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Pyrrolidines / pharmacology
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RNA / chemistry
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Reverse Transcriptase Polymerase Chain Reaction
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Superantigens / metabolism*
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T-Lymphocytes / metabolism
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Thiocarbamates / pharmacology
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Up-Regulation
Substances
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Amino Acid Chloromethyl Ketones
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Antibodies, Monoclonal
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B7-1 Antigen
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DNA, Complementary
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Enterotoxins
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Enzyme Inhibitors
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NF-kappa B
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Pyrrolidines
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Superantigens
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Thiocarbamates
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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pyrrolidine dithiocarbamic acid
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enterotoxin B, staphylococcal
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RNA
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Interferon-gamma
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CASP3 protein, human
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CASP8 protein, human
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Caspase 3
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Caspase 8
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Caspases