Suppression of endotoxin- and staphylococcal exotoxin-induced cytokines and chemokines by a phospholipase C inhibitor in human peripheral blood mononuclear cells.
Excessive release of proinflammatory cytokines from cells stimulated with lipopolysaccharide (LPS) or staphylococcal exotoxin (SE) mediates the pathophysiologic manifestations of septic shock. Tricyclodecan-9-yl (D609), an inhibitor of phosphatidylcholine-specific phospholipase C, suppressed LPS- or SE-induced cytokines and chemokines in human peripheral blood mononuclear cells. These data suggest a potential role for D609 in the treatment of septic shock.
Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Maryland 21702-5011, USA. teresa.krakauer@det.amedd.army.mil
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D001952:Bridged-Ring Compounds / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism*; D054407:Chemokine CCL4; D016207:Cytokines / Q000378:metabolism*; D005098:Exotoxins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D001952:Bridged-Ring Compounds; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D016207:Cytokines; D005098:Exotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D009636:Norbornanes; D010726:Phosphodiesterase Inhibitors; D013859:Thiocarbamates; D013871:Thiones; D014409:Tumor Necrosis Factor-alpha; C416085:staphylococcal exotoxin 1; C046498:tricyclodecane-9-yl-xanthogenate; D007371:Interferon-gamma; D010738:Type C Phospholipases