The potency of anti-oxidants in attenuating superantigen-induced proinflammatory cytokines correlates with inactivation of NF-kappaB.
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.
Krakauer
Teresa
T
Department of Immunology, Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA. teresa.krakauer@amedd.army.mil
Buckley
Marilyn
M
D000111:Acetylcysteine / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004768:Enterotoxins / Q000276:immunology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology*; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013859:Thiocarbamates / Q000494:pharmacology*; D000099192:CD69 Antigens
D000111:Acetylcysteine; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000975:Antioxidants; D016207:Cytokines; D004768:Enterotoxins; D005978:Glutathione; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D016328:NF-kappa B; D011759:Pyrrolidines; D018089:Superantigens; D013859:Thiocarbamates; D000099192:CD69 Antigens; C020972:pyrrolidine dithiocarbamic acid; C031818:enterotoxin B, staphylococcal