scholarly journals Neutralization of Staphylococcal Enterotoxin B by an Aptamer Antagonist

2015 ◽  
Vol 59 (4) ◽  
pp. 2072-2077 ◽  
Author(s):  
Kaiyu Wang ◽  
Longjie Gan ◽  
Li Jiang ◽  
Xianhui Zhang ◽  
Xiangyue Yang ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Toxic Shock ◽  
Peripheral Blood Mononuclear ◽  
Systematic Evolution ◽  
Enterotoxin B ◽  
Staphylococcal Toxic Shock Syndrome ◽  
Exponential Enrichment

ABSTRACTStaphylococcal enterotoxin B (SEB) is a major virulence factor for staphylococcal toxic shock syndrome (TSS). SEB activates a large subset of the T lymphocytic population, releasing proinflammatory cytokines. Blocking SEB-initiated toxicity may be an effective strategy for treating TSS. Using a process known as systematic evolution of ligands by exponential enrichment (SELEX), we identified an aptamer that can antagonize SEB with nanomolar binding affinity (Kd= 64 nM). The aptamer antagonist effectively inhibits SEB-mediated proliferation and cytokine secretion in human peripheral blood mononuclear cells. Moreover, a PEGylated aptamer antagonist significantly reduced mortality in a “double-hit” mouse model of SEB-induced TSS, established via sensitization withd-galactosamine followed by SEB challenge. Therefore, our novel aptamer antagonist may offer potential therapeutic efficacy against SEB-mediated TSS.

scholarly journals Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine Release InVitro and In Vivo

2010 ◽  
Vol 54 (3) ◽  
pp. 1125-1131 ◽  
Author(s):  
Teresa Krakauer ◽  
Marilyn Buckley ◽  
Haleem J. Issaq ◽  
Stephen D. Fox
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Toxic Shock ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Enterotoxin B

ABSTRACT Staphylococcal enterotoxins are potent activators for human T cells and cause lethal toxic shock. Rapamycin, an immunosuppressant, was tested for its ability to inhibit staphylococcal enterotoxin B (SEB)-induced activation of human peripheral blood mononuclear cells (PBMC) in vitro and toxin-mediated shock in mice. Stimulation of PMBC by SEB was effectively blocked by rapamycin as evidenced by the inhibition of tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), IL-6, IL-2, gamma interferon (IFN-γ), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and T-cell proliferation. In vivo, rapamycin protected 100% of mice from lethal shock, even when administered 24 h after intranasal SEB challenge. The serum levels of MCP-1 and IL-6, after intranasal exposure to SEB, were significantly reduced in mice given rapamycin versus controls. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB.

scholarly journals Pirfenidone Blocks the In Vitro and In Vivo Effects of Staphylococcal Enterotoxin B

2002 ◽  
Vol 70 (6) ◽  
pp. 2989-2994 ◽  
Author(s):  
Martha L. Hale ◽  
Solomon B. Margolin ◽  
Teresa Krakauer ◽  
Chad J. Roy ◽  
Bradley G. Stiles
Keyword(s):  
Human Peripheral Blood ◽  
Biological Effects ◽  
Interleukin 1 ◽  
Staphylococcal Enterotoxin ◽  
Sublethal Dose ◽  
Staphylococcal Enterotoxin B ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Enterotoxin B

ABSTRACT Pirfenidone [5-methyl-1-phenyl-2-(1H)-pyridone] down-regulates expression of cytokines and other mediators involved in the onset and development of pulmonary fibrosis. Pirfenidone also inhibits production of tumor necrosis factor alpha (TNF-α) from macrophages incubated with endotoxin and protects mice against endotoxin shock. Pirfenidone's ability to reduce cytokine expression in these disorders led us to investigate the drug's effect on another cytokine anomaly, superantigen-induced shock. BALB/c mice were exposed to staphylococcal enterotoxin B (SEB) either systemically or by aerosol and subsequently potentiated with a sublethal dose of lipopolysaccharide. In these experiments, pirfenidone given 2 to 4.25 h after SEB resulted in 80 to 100% survival versus only 0 to 10% survival among untreated control animals. Relative to serum cytokine levels from controls given toxin but no drug, there was a 35 to 80% decrease in TNF-α, interleukin 1, and other proinflammatory cytokines. In vitro experiments with human peripheral blood lymphocytes revealed that pirfenidone reduced SEB-induced cytokine levels 50 to 80% and inhibited 95% of SEB-induced T-cell proliferation. Overall, these studies demonstrated the potential utility of pirfenidone as a therapeutic against septic shock and the biological effects of SEB.

scholarly journals Caspase Inhibitors Attenuate Superantigen-Induced Inflammatory Cytokines, Chemokines, and T-Cell Proliferation

2004 ◽  
Vol 11 (3) ◽  
pp. 621-624 ◽  
Author(s):  
Teresa Krakauer
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Therapeutic Modality ◽  
T Cell Proliferation ◽  
Toxic Shock ◽  
Peripheral Blood Mononuclear ◽  
Caspase Inhibitors ◽  
Cytokines And Chemokines

ABSTRACT 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.

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