Inhibition of nuclear factor-kappa B prevents staphylococcal enterotoxin A-induced fever.
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-kappaB) 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-kappaB mechanisms in human PBMC are involved in SEA-induced fever. Western blot evaluation revealed SEA was able to induce nuclear translocation of NF-kappaB from cytosol to nucleus in PBMC, which could be abolished by a NF-kappaB 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-kappaB DNA-binding activity was increased in the SEA-treated PBMC. Again, the SEA-induced increased NF-kappaB 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-beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) in the supernatant fluids. Both the fever and the increased levels of IL-1beta, IL-6, and TNF-alpha 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-kappaB prevents SEA-induced fever.
Shao
Dong-Zi
DZ
Department of Medical Research Chi-Mei Medical Center, Tainan Hsien, Taiwan, ROC.
Lee
Jie-Jen
JJ
Huang
Wu-Tein
WT
Liao
Jyh-Fei
JF
Lin
Mao-Tsun
MT
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001831:Body Temperature; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004768:Enterotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology
D016207:Cytokines; D004768:Enterotoxins; D016328:NF-kappa B; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; C026066:enterotoxin A, Staphylococcal; D011392:Proline