Triptolide attenuates endotoxin- and staphylococcal exotoxin-induced T-cell proliferation and production of cytokines and chemokines.
Proinflammatory cytokines mediate the toxic effects of superantigenic staphylococcal exotoxins (SE) and bacterial lipopolysaccharide (LPS). Triptolide, an oxygenated diterpene derived from a traditional Chinese medicinal herb, Tripterygium wilfordii, inhibited SE-stimulated T-cell proliferation (by 98%) and expression of interleukin 1beta, interleukin 6, tumor necrosis factor, gamma interferon, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta by human peripheral blood mononuclear cells (PBMC). It also blocked the production of these cytokines and chemokines by LPS-stimulated PBMC in a dose-dependent manner. These results suggest that triptolide has potent immunosuppressive effects even counteracting the effects of superantigens and LPS. It also may be therapeutically useful for mitigating the pathogenic effects of these microbial products by downregulating the signaling pathways activated by both bacterial exotoxins and endotoxins.
Krakauer
Teresa
T
Department of Immunology and Molecular Biology, United States Army Medical Research Institute of Infectious Diseases, Bldg. 1425, Fort Detrick, Frederick, MD 21702-5011, USA. Teresa.Krakauer@det.amedd.army.mil
Chen
Xin
X
Howard
O M Zack
OM
Young
Howard A
HA
D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D001427:Bacterial Toxins; D018925:Chemokines; D016207:Cytokines; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004731:Endotoxins; D004768:Enterotoxins; D004852:Epoxy Compounds; D010616:Phenanthrenes; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C001899:triptolide