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Staphylococcal enterotoxin C1‐induced pyrogenic cytokine production in human peripheral blood mononuclear cells is mediated by NADPH oxidase and nuclear factor‐kappa B
Author(s) -
Su ChunLi,
Cheng ChunChun,
Lin MaoTsun,
Yeh HsiaoChun,
Lee MengChou,
Lee JenqChang,
Won ShenJeu
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05896.x
Subject(s) - nadph oxidase , apocynin , peripheral blood mononuclear cell , enterotoxin , chemistry , pyrrolidine dithiocarbamate , cytokine , reactive oxygen species , microbiology and biotechnology , immunology , biology , biochemistry , in vitro , signal transduction , nf κb , escherichia coli , gene
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 p47 phox 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 p47 phox 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.