Caspase inhibitors attenuate superantigen-induced inflammatory cytokines, chemokines, and T-cell proliferation.
Proinflammatory cytokines mediate the toxic effect of superantigenic staphylococcal exotoxins (SE). A pan-caspase inhibitor suppressed SE-stimulated T-cell proliferation and the production of cytokines and chemokines by human peripheral blood mononuclear cells. These data suggest that caspase inhibitors may represent a novel therapeutic modality for treating SE-induced toxic shock.
Krakauer
Teresa
T
Department of Immunology and Molecular Biology, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA. teresa.krakauer@det.amedd.army.mil
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D001427:Bacterial Toxins; C111835:CCL2 protein, human; D061945:Caspase Inhibitors; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; D015853:Cysteine Proteinase Inhibitors; D016207:Cytokines; D004768:Enterotoxins; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D009842:Oligopeptides; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C093260:benzyloxycarbonyl-Asp-CH2OC(O)-2,6-dichlorobenzene; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C030107:enterotoxin F, Staphylococcal; D001224:Aspartic Acid; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma; D020169:Caspases