Tài liệu Báo cáo khoa học: Staphylococcal enterotoxin C1-induced pyrogenic cytokine production in

Staphylococcal enterotoxin C1-induced pyrogenic

cytokine production in human peripheral blood

mononuclear cells is mediated by NADPH oxidase and

nuclear factor-kappa B

Chun-Li Su1

, Chun-Chun Cheng2

, Mao-Tsun Lin3

, Hsiao-Chun Yeh2

, Meng-Chou Lee2

,

Jenq-Chang Lee4 and Shen-Jeu Won2

1 Department of Nursing, Chang Jung Christian University, Tainan, Taiwan

2 Department of Microbiology and Immunology, Medical College, National Cheng Kung University, Tainan, Taiwan

3 Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan

4 Department of Surgery, Medical College, National Cheng Kung University, Tainan, Taiwan

Staphylococcus aureus is a major food-borne pathogen

which produces a number of toxins and virulence fac￾tors [1]. The staphylococcal enterotoxins produced by

S. aureus are known to cause staphylococcal food

poisoning, fever, and toxic shock syndrome, and also

act as immunosuppressors and affect cytokine

Keywords

human peripheral blood mononuclear cells;

NADPH oxidase; NF-jB; pyrogenic cytokine;

staphylococcal enterotoxin C1

Correspondence

S.-J. Won, Department of Microbiology and

Immunology, Medical College, National

Cheng Kung University, no. 1, Ta-Hsueh

Road, Tainan 701, Taiwan

Fax: +886 6 2082705

Tel: +886 6 2744435

E-mail: [email protected]

(Received 2 April 2007, revised 17 May

2007, accepted 22 May 2007)

doi:10.1111/j.1742-4658.2007.05896.x

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-jB) 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 superna￾tant fluids of SEC1-stimulated PBMC in rabbits was in parallel with the

levels of interleukin-1b and interleukin-6 in the supernatants. The release

of interleukin-1b and interleukin-6, nuclear translocation of NF-jB and its

DNA binding activity in the SEC1-stimulated PBMC were time-dependent

and were completely eliminated by pyrrolidine dithiocarbamate or SN-50

(NF-jB inhibitors). The release of reactive oxygen species in the super￾natants 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 transloca￾tion of NADPH oxidase p47phox subunit and NF-jB 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-jB in PBMC to stimulate the synthesis of pyrogenic

cytokines that trigger a fever response in rabbits.

Abbreviations

Apo, apocynin; EMSA, electrophoretic mobility shift assay; ETYA, 5,8,11,14-eicosatetraynoic acid; FLAP, 5-LOX-activating protein; HBSS,

Hanks’ balanced salt solution; HIMO, 1L-6-hydroxymethyl-chiro-inositol-2(R)-2-O-methyl-3-O-octadecylcarbonate; IL, interleukin; 5-LOX,

5-lipoxygenase; MK 886, 3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-t-butylthioindol-2-yl]-2,2-dimethylpropanoic acid; NF-jB, nuclear factor-kappa B;

PBMC, human peripheral blood mononuclear cells; PDTC, pyrrolidine dithiocarbamate; PI3K, phosphatidylinositol-3-kinase; ROS, reactive

oxygen species; SEs, staphylococcal enterotoxins; SEC1, staphylococcal enterotoxin C1; SP, supernatant fluids of SEC1-stimulated PBMC;

TSST-1, toxic shock syndrome toxin-1; Wort, wortmannin.

FEBS Journal 274 (2007) 3633–3645 ª 2007 The Authors Journal compilation ª 2007 FEBS 3633