Abstract
Excessive release of proinflammatory cytokines and chemokines mediates the toxic effects of superantigenic staphylococcal exotoxins (SE). We evaluated the potency of two anti-oxidants, N-acetyl-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) in inhibiting the staphylococcal enterotoxin B and staphylococcal toxic shock syndrome-1-induced activation of human peripheral blood mononuclear cells (PBMC). Both NAC and PDTC dose-dependently inhibited SE-stimulated T-cell proliferation (by 98%), production of cytokines and chemokines by PBMC and expression of SE-induced cell surface activation markers. The potency of both NAC and PDTC corresponded to their ability to inhibit NF-kappaB activation. Our results suggest that anti-oxidants might be useful to mitigate the pathogenic effects of SE by blocking transcriptional signaling activated by superantigens.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acetylcysteine / pharmacology*
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Antigens, CD / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Antioxidants / pharmacology*
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Cells, Cultured
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Cytokines / antagonists & inhibitors*
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Enterotoxins / immunology
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Glutathione / metabolism
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Humans
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Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
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Lectins, C-Type
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Lymphocyte Activation / drug effects
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Monocytes / drug effects
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Monocytes / immunology
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NF-kappa B / antagonists & inhibitors*
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Pyrrolidines / pharmacology*
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Superantigens / immunology
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology
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Thiocarbamates / pharmacology*
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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Antioxidants
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CD69 antigen
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Cytokines
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Enterotoxins
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Interleukin-2 Receptor alpha Subunit
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Lectins, C-Type
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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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pyrrolidine dithiocarbamic acid
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enterotoxin B, staphylococcal
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Glutathione
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Acetylcysteine