Staphylococcal enterotoxin C1‐induced pyrogenic cytokine production in human peripheral blood mononuclear cells is mediated by NADPH oxidase and nuclear factor‐kappa B

The staphylococcal enterotoxins produced by Staphylococcus aureus are associated with pyrogenic response in humans and primates. This study investigates the role of NADPH oxidase and nuclear factor‐kappa B (NF‐κB) on enterotoxin staphylococcal enterotoxin C1 (SEC1)‐induced pyrogenic cytokine product...

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Bibliographic Details
Published in:The FEBS journal 2007-07, Vol.274 (14), p.3633-3645
Main Authors: Su, Chun‐Li, Cheng, Chun‐Chun, Lin, Mao‐Tsun, Yeh, Hsiao‐Chun, Lee, Meng‐Chou, Lee, Jenq‐Chang, Won, Shen‐Jeu
Format: Article
Language:English
Subjects:
Animals
Arachidonate 5-Lipoxygenase - metabolism
Biochemistry
Cells, Cultured
Cellular biology
Cytokines
Enterotoxins - pharmacology
Enzyme Inhibitors - pharmacology
Fever
Flap Endonucleases - metabolism
human peripheral blood mononuclear cells
Humans
Interleukin-1beta - biosynthesis
Interleukin-6 - biosynthesis
Leukocytes - drug effects
Leukocytes - metabolism
Leukocytes - secretion
Male
NADPH oxidase
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
NF-kappa B - metabolism
NF‐κB
Phosphorylation - drug effects
Primates
Protein Transport
pyrogenic cytokine
Rabbits
Reactive Oxygen Species - metabolism
staphylococcal enterotoxin C1
Staphylococcus aureus
Staphylococcus infections
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Summary:The staphylococcal enterotoxins produced by Staphylococcus aureus are associated with pyrogenic response in humans and primates. This study investigates the role of NADPH oxidase and nuclear factor‐kappa B (NF‐κB) on enterotoxin staphylococcal enterotoxin C1 (SEC1)‐induced pyrogenic cytokine production in human peripheral blood mononuclear cells (PBMC). The results indicate that the febrile response to the supernatant fluids of SEC1‐stimulated PBMC in rabbits was in parallel with the levels of interleukin‐1β and interleukin‐6 in the supernatants. The release of interleukin‐1β and interleukin‐6, nuclear translocation of NF‐κB and its DNA binding activity in the SEC1‐stimulated PBMC were time‐dependent and were completely eliminated by pyrrolidine dithiocarbamate or SN‐50 (NF‐κB inhibitors). The release of reactive oxygen species in the supernatants and translocation of the NADPH oxidase p47phox subunit to the plasma membrane of SEC1‐stimulated PBMC were time‐dependent. Administration of apocynin (NADPH oxidase inhibitor) attenuated the febrile response to the supernatants in rabbits and decreased the translocation of NADPH oxidase p47phox subunit and NF‐κB activity in the SEC1‐stimulated PBMC, and suppressed reactive oxygen species and pyrogenic cytokine production in the supernatants. Taken together, SEC1 may act through an NADPH oxidase mechanism to release reactive oxygen species, which activate NF‐κB in PBMC to stimulate the synthesis of pyrogenic cytokines that trigger a fever response in rabbits.
ISSN:1742-464X
1742-4658
DOI:10.1111/j.1742-4658.2007.05896.x