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Inhibition of nuclear factor-kappa B prevents staphylococcal enterotoxin A-induced fever

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Abstract

It has been shown that staphylococcal enterotoxin A (SEA) acts through human peripheral blood mononuclear cells (PBMC) to stimulate synthesis or release of pyrogenic cytokines. Nuclear factor-kappa B (NF-κB) is thought to play an important role in inflammatory responses through the regulation of genes encoding pro-inflammatory cytokines. The purpose of the present study was to determine whether the NF-κB mechanisms in human PBMC are involved in SEA-induced fever. Western blot evaluation revealed SEA was able to induce nuclear translocation of NF-κB from cytosol to nucleus in PBMC, which could be abolished by a NF-κB inhibitor such as pyrrolidine dithiocarbamate (PDTC), sodium pyrithione (Pyri), N-acetyl-L-cysteine (NAC), or curcumin (Cur). Electrophoretic mobility shift assay also showed that the NF-κB DNA-binding activity was increased in the SEA-treated PBMC. Again, the SEA-induced increased NF-κB binding activity was significantly attenuated by either PDTC, Pyri, NAC or Cur. The pyrogenic responses to supernatant fluids obtained from human PBMC stimulated with SEA were associated with increased levels of interleukin 1-β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in the supernatant fluids. Both the fever and the increased levels of IL-1β, IL-6, and TNF-α in supernatant fluids obtained from the SEA-stimulated PBMC were decreased by incubating SEA-PBMC with either PDTC, Pyri, NAC, or Cur. Furthermore, the fever induced by systemic or central administration of SEA in rabbits were attenuated by pre-treatment with an systemic or central dose of either PDTC, Pyri, NAC, or Cur. The data indicate that inhibition of NF-κB prevents SEA-induced fever. (Mol Cell Biochem 262: 177–185, 2004)

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Authors and Affiliations

  1. Department of Medical Research Chi-Mei Medical Center, Tainan Hsien, Taiwan, ROC

    Dong-Zi Shao & Mao-Tsun Lin

  2. Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC

    Jie-Jen Lee

  3. Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan, ROC

    Jie-Jen Lee

  4. Diwan University, Matou, Tainan Hsien, Taiwan, ROC

    Wu-Tein Huang

  5. Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC

    Jyh-Fei Liao

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  1. Dong-Zi Shao
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  4. Jyh-Fei Liao
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  5. Mao-Tsun Lin
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Shao, DZ., Lee, JJ., Huang, WT. et al. Inhibition of nuclear factor-kappa B prevents staphylococcal enterotoxin A-induced fever. Mol Cell Biochem 262, 177–185 (2004). https://doi.org/10.1023/B:MCBI.0000038233.20276.e0

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  • DOI: https://doi.org/10.1023/B:MCBI.0000038233.20276.e0

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