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研究生:嚴文姝
論文名稱:腸炎沙門氏桿菌的毒性質體會增進宿主細胞間素12(Interlukin-12)之次單位,p40的大量產生
論文名稱(外文):Enhanced production of p40, a subunit of interleukin-12, by mouse macrophages stimulated by Salmonella enterica serovar Enteritidis virulence plasmid
指導教授:歐炯雄
學位類別:碩士
校院名稱:長庚大學
系所名稱:基礎醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:49
中文關鍵詞:腸炎沙門氏桿菌細胞間素
外文關鍵詞:Salmonella enteritidisIL-12p40
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沙門氏菌是屬於腸內細菌科(Enterobacteriaceae),有兩千種以上的血清型,其中Salmonella enterica serovar Enteritidis是目前常見引起腸胃炎的沙門氏菌。Enteritidis以家禽類為其主要宿主,家禽如果感染Enteritidis,則所生的蛋中,也會帶有Enteritidis。人如果食用此種未煮熟的蛋,很容易引起腸胃炎,食物中毒,系統性感染,甚至是菌血症等疾病。而另一血清型, Salmonella enterica serovar Typhimurium,在之前的研究中發現其毒性質體可以刺激宿主吞噬細胞產生大量IL-12 p40 [interleukin-12(IL-12,分子量70kDa)分子量40kDa的次單位],Enteritidis的毒性質體與Typhimurium的毒性質體很相似,因此做一連串的實驗以探討Enteritidis的質體是否也具有刺激p70及p40功能,而從結果可知,Enteritidis的質體也具有同樣的功能,亦即刺激微量p70,卻刺激大量p40的產生。使用Tn5插入之突變菌株的結果,顯示其中Tn5插入位置(在H2片段上)可能與Typhimurium的質體上刺激p40的遺傳位置相同,另外尚有兩位置與刺激p40有關。Homodimer的p40也會和IL-12的receptor結合,但不具有IL-12的生物活性,不會活化該白血球細胞。因此IL-12 p40的大量產生,可造成對IL-12p70的競爭性抑制,進一步抑制宿主的免疫反應,如此IL-12p40的大量產生可能是一致病因子。以老鼠做毒性試驗結果,有一野生型Enteritidis比一Tn5突變菌株的質體,雖刺激大量的IL-12p40,卻顯示較低的毒性,其原因不明。

Non-typhoid salmonellae containing virulence plasmid are highly associated with bacteremia and disseminated infection in humans. There are more than 2000 Salmonella serovars. Salmonella enterica servoar Enteritidis is one of the 2000 serovars, and its infection is a major cause of food-born illness, causing gastroenteritis in human worldwide. The virulence plasmid of Salmonella enterica servoar Typhimurium (pSTV) has been shown to enhance IL-12p40, a subunit of IL-12p70 (the other subunit is IL-12p35), production in the mouse. DNA-DNA hybridization analysis indicates that pSTV (~90 kb) contains a region hybridizing to virtually all of the Enteritidis plasmid (pSEV) and ninety-nine percent homology is found between pSTV and pSEV. Since pSEV is a plasmid closely related to pSTV, we performed experiments to check, ex vivo, whether or not pSEV was also similarly involved in the production of IL-12p40 in the mouse peritoneal macrophage upon infection with various strains of Enteritidis. We found that pSEV also stimulated macrophages to produce IL-12p40 and the stimulation appeared to involve pSEV. The Enteritidis strains harboring Tn5-inserted pSEV generally showed a lower level of IL-12p40 production than wild type Enteritidis, indicating that pSEV might also carry some loci, that enhanced the production of IL-12p40 in mouse peritoneal macrophages. A homodimer of IL-12p40 has been shown to competitively antagonize the activity of IL-12p70. Perhaps one mechanism utilized by Salmonella to evade cell-mediated immune response is the ability to enhance IL-12p40 production, that, in turn, inhibits generation of immunity.

中文摘要2
英文摘要3
前言5
實驗方法與材料16
結果28
討論39
參考文獻45

張鑑中, 歐炯雄. 鼠傷寒沙門氏菌的毒性質體上具有基因能增進宿主細胞間素12 (Interleukin-12)之次單位,p40,的大量產生. 長庚大學基礎醫學研究所碩士論文. 1998, July
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