Staphylococcal Enterotoxin C1 Acts through NF-kB Pathway to Stimulate the Production of Pyrogenic Cytokines in Human Peripheral Blood Mononuclear Cells

• Main Authors: Hsiao-Chun Yeh, 葉孝駿
• Other Authors: Shen-Jeu Won
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/98789267987247302781

碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 88 === The pyrogenic responses to supernatant fluids obtained from human peripheral blood mononuclear cells (PBMC) stimulated with staphylococcal enterotoxin C1 (SEC1) required activation of NF-kB to trigger endogenous pyrogenic cytokine productions. In order to ascertain the possible roles of pyrogenic cytokines in the development of SEC1 fever, experiments were carried out to assess both the body temperatures in rabbits and the pyrogenic cytokine productions including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 in SEC1-treated PBMC supernatants. Intravenous injection of the supernatant fluids obtained from SEC1-treated PBMC caused a dose-related fever in rabbits. The levels of TNF, IL-1, or IL-6 in the supernatant fluids started to rise at 12 h and reached their peak levels at 72 to 96 h after SEC1 stimulation. Both of the febrile response and the increases of IL-1, IL-6, and TNF in the supernatant fluids obtained from SEC1-treated PBMC were attenuated by incubating SEC1-PBMC with dexamethasone (10-6 M, an inflammatory and immunosuppressive inhibitor), pyrrolidine dithiocarbamate (PDTC, 10-3 M), pyrithione (10-4 M) or curcumin (10-4 M) (the later three compounds are NF-kB inhibitors), but not with aminoguanidine (8×10-4 M, an inducible nitric oxide synthase inhibitor). The translocation of NF-kB from cytosols to nuclei was observed in SEC1-treated PBMC. Dexamethasone, PDTC, pyrithione, or curcumin, but not aminoguanidine, inhibited NF-kB activation. These results indicate that SEC1 may act through NF-kB pathway in PBMC to stimulate the synthesis of pyrogenic cytokines, therefore, to induce febrile response.