系統識別號 U0026-0812200910443084
論文名稱(中文) NADPH oxidase抑制劑apocynin抑制 葡萄球菌腸內毒素C1誘導致熱性細胞素之產生
論文名稱(英文) NADPH oxidase inhibitor apocynin suppresses pyrogenic cytokine productions induced by Staphylococcal enterotoxin C1
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 91
學期 2
出版年 92
研究生(中文) 鄭淳淳
研究生(英文) Chun-Chun Cheng
電子信箱 sonatinen1109@yahoo.com.tw
學號 s4690405
學位類別 碩士
語文別 中文
論文頁數 88頁
口試委員 口試委員-林忠男
中文關鍵字 活性氧化物  致熱性毒素  發燒  葡萄球菌腸內毒素C1 
英文關鍵字 SEC1  NADPH oxidase  NF-κB  pyrogenic cytokine 
中文摘要 本實驗首度證明葡萄球菌腸內毒素C1 (staphylococcal enterotoxin C1, SEC1) 刺激人類週邊單核細胞後,可藉由活化NADPH oxidase產生superoxide anion (O2.-),繼而活化下游的NF-κB相關路徑,誘導致熱性細胞素的產生,導致兔子的發燒反應。實驗中以SEC1刺激PBMC後,所收集的上清液,將其以靜脈注射至兔子體內,可觀察到兔子發燒的情形。此外,上清液中也可以偵測到O2.-的產生、與大量的IL-1β 和TNF-α 致熱性細胞激素。以西方墨點法 (Western blot analysis) 觀察到IKK-β 與IκB-α 有被磷酸化的情形,同時IκB-α 也有漸減的情況;並且也觀察到NADPH oxidase的次分子p47phox從細胞質轉移到細胞膜的情況。然而由Western blot analysis與EMSA的分析,觀察到NF-κB/p65有從細胞質移入細胞核的現象並且具有與DNA結合的能力。當處理NDAPH oxidase的抑制劑-apocynin與NF-κB的抑制劑-PDTC或SN-50,可使經SEC1刺激PBMC所產生的IL-1β、TNF-α 與O2.-的量受到抑制。SEC1刺激PBMC後可誘導p47phox移動到膜上與NF-κB入核,這樣的情形也會受到apocynin、PDTC、與SN-50給抑制。同樣的,SEC1刺激PBMC後的上清液會引起兔子發燒的情形也可被apocynin、PDTC與SN-50所抑制。因此經由實驗證實SEC1可能透過NADPH oxidase的活化進而導致NF-kB相關路徑活化,誘導致熱性細胞素的產生導致兔子的發燒情形。
英文摘要 Staphylococal enterotoxins (SEs), produced by Staphylococcus aureus, are known to cause most common staphylococcal food poisoning, fever, toxic shock syndrome, and causes the productions of cytokines in humans and primates. In order to investigate the mechanism of SEC1-induced pyrogenic response, rabbits were intravenously injected with the supernatants of obtained from SEC1-treated human peripheral blood mononuclear cells (PBMC). The concentration of O2.- and pyrogenic cytokines such as IL-1β and TNF-α in the supernatant fluids obtained from the SEC1-treated PBMC were increased in a dose- and time-dependent manner. Time dependency study exhibited SEC1 subsequently caused the movement of NADPH oxidase p47phox subunit from the cytosol to cell membrane, phosphorylation of IKK-β and IkB-α, translocation of p65 subunit of NF-κB, and increased NF-κB- DNA binding activity. Moreover, apocynin, a NADPH oxidase inhibitor, inhibited the translocation of NADPH oxidase p47phox, and also the O2.- production in SEC1-treated PBMC. NF-κB inhibitor, PDTC or SN-50, did not suppressed the production of O2.- but decreased the releases of pyrogenic cytokines in the supernatant fluids of the SEC1-treated PBMC. Nuclear p65 expression and NF-κB DNA binding activity were inhibited by PDTC, SN-50 in SEC1 PBMC. The febrile responses induced by intravenous administration of the supernatant fluids obtained from the SEC1-treated PBMC were significantly reduced by adding apocynin or PDTC into the SEC1-treated PBMC incubation. Thus, it appears that apocynin inhibits the SEC1 induced NADPH oxidase to release O2.- , which in turn activating the NF-κB related pathway and the synthesis and releases of pyrogenic cytokines in the PBMC to trigger febrile response.
論文目次 中文摘要…………………………………………………………….. II
英文摘要…………………………………………………………….. III
表目錄……………………………………………………….…….… IV
圖目錄……………………………………….………….…………… VI
誌謝………………………………………………………………….. VIII
緒論…………………………………………………………………. 1
材料與方法………………………………………………………….. 11
結果………………………………………………………………….. 28
討論……………………………………………………………….…. 36
參考文獻…………………………………………………………….. 39
附表…………………………………………………………..……… 58
附圖………………………………………………………………….. 69
參考文獻 黃戊田 (民87) 葡萄球菌腸內毒素A之致熱作用。國立成功大學微生物及免疫學研究所博士論文,頁1-16。中華民國,台南。
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