出版年:

2000

研究生:

葉孝駿

研究生(英文姓名):

Hsiao-Chun Yeh

論文名稱:

金黃色葡萄球菌腸毒素C1刺激人類週邊單核細胞經由NF-κB途徑產生致熱性細胞素

英文論文名稱:

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

指導教授:

翁舷誌 博士

指導教授(英文姓名):

Dr. Shen-Jeu Won

學位類別:

碩士

校院名稱:

國立成功大學　

系所名稱:

微生物暨免疫學研究所

學號:

s46871039

學年度:

88

語文別:

中文

論文頁數:

76

關鍵詞:

金黃色葡萄球菌腸毒素C1 ; NF-κB ; 致熱性細胞素

英文關鍵詞:

Staphylococcal Enterotoxin C1 ; NF-κB ;
Pyrogenic Cytokines

被引用次數:

0

[ 摘要 ]

金黃色葡萄球菌腸毒素C1 (SEC1)刺激人類週邊單核細胞 (human peripheral blood mononuclear cells, PBMC) 會經由活化NF-kB而使致熱性細胞素大量產生進而引起發燒。為了探討SEC1引起發燒反應中致熱性細胞素所扮演的角色，以SEC1刺激人類週邊單核細胞後所得之上清液靜脈注射兔子觀察其體溫變化，並分析此上清液是否產生致熱性細胞素，如腫瘤壞死因子 (tumor necrosis factor, TNF)、第一介白質 (interleukin-1, IL-1)、及第六介白質 (IL-6)。結果顯示，將SEC1刺激PBMC後之上清液靜脈注射到兔子體內，會引起劑量相關性的發燒反應，同時上清液中之TNF、IL-1及IL-6亦有增加的現象。致熱性細胞素TNF、IL-1及IL-6在SEC1刺激PBMC後12小時開始產生而在72至96小時左右達到最高量。SEC1刺激PBMC後在上清液中大量釋放TNF、IL-1及IL-6等致熱性細胞素及之後所引起的發燒反應會在同時加入dexamethasone (抗發炎劑及免疫抑制劑，10-6 M)及三種 NF-kB的抑制劑pyrrolidine dithiocarbamate ( PDTC, 10-3 M)、pyrithione ( 10-4 M) 和 curcumin ( 10-4 M)後而被抑制，但在加入aminoguanidine (NOS抑制劑，8×10-4 M)後並無抑制現象。而西方點墨法的結果顯示SEC1刺激PBMC後其細胞核內會有NF-kB增加的現象，且dexamethasone、PDTC、pyrithione及curcumin都會抑制SEC1刺激PBMC核內 NF-kB量的增加，若在 SEC1刺激PBMC的同時加入aminoguanidine則無此抑制現象。綜合上述實驗結果顯示，SEC1刺激PBMC後會藉由活化NF-kB途徑去刺激細胞素的合成進而媒介SEC1的發燒反應。

[ 英文摘要 ]

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.