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研究生:張建仁
研究生(外文):Chien-Jen Chang
論文名稱:Nod2基因突變增強巨噬細胞的NF-kappaB活動及殺菌活動
論文名稱(外文):Nod2 Mutation Enhances NF-kappaB activity and Bacterial Killing Activity of Macrophages
指導教授:陳理維陳理維引用關係
指導教授(外文):Lee-Wei Chen
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:急重症醫學研究所
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:2009
畢業學年度:97
語文別:中文
論文頁數:62
中文關鍵詞:巨噬細胞殺菌活動
外文關鍵詞:NOD2IL-1bbacterial killing activityTNFaNF-kB
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NOD2蛋白是細胞內的細菌感應器,它和 Crohn’s Disease (CD) 患者容易被細菌刺激有關聯,主要表現是在巨噬細胞 (macrophage) 和樹突狀細胞 (dendritic cells) 。本研究的目的是要檢視 NOD2 在巨噬細胞被細菌刺激時,所表現的原始反應中扮演的角色。首先,我們先從 wild type (WT)、Nod2 2939iC 型、及 TLR4-/- 型的老鼠腹膜腔和肺泡中獲取巨噬細胞,再拿來和大腸桿菌 (E. coli) 及綠膿桿菌(Pseudomonas aeruginosa)一起作用。之後,分別分析巨噬細胞的殺菌活動 (bacterial killing activity) , IL-1β 及 Toll-like receptor 4 (TLR4) 蛋白質的表現, NF-κB DNA 結合活動 (NF-κB DNA binding activity) 和 IL-1β、TNFα、TLR2、 TLR4、及TLR9 的 mRNA 表現。結果,我們發現 Nod2 2939iC 型老鼠的腹膜腔及肺泡巨噬細胞對大腸桿菌作用後,呈現較強的殺菌活性,但在 WT 及 TLR4-/- 型的老鼠就無此現象。在和細菌作用後, Nod2 2939iC 型老鼠的腹膜腔巨噬細胞也表現出較高的 pro-IL-1β 蛋白質產量、 較強的NF-κB DNA 結合活動、及較增多的 IL-1β、TNFα mRNA 表現量。總括,在 Nod2 2939iC 型老鼠的巨噬細胞所發現的增強的殺菌活動、增強的 IL-1β 表現、及 NF-κB的DNA 結合活動,都顯示, NOD2 是 CD 患者在受到細菌刺激時,藉由 NF-κB/IL-1β 媒介路徑所產生的原始免疫反應 (innate response) 中的正向調控因子。並且 Nod2 2939iC 造成老鼠巨噬細胞產生較為強烈的殺菌活動。
NOD2, an intracellular sensor of bacteria, are linked to increased susceptibility to bacteria in Crohn’s disease (CD). The NOD2 protein is expressed mainly by macrophages and dendritic cells. This study is to examine the role of NOD2 in the innate response of macrophages to bacterial challenge. First, peritoneal macrophages and alveolar macrophages were harvested from WT, Nod22939iC, as well as TLR4-/- mice and incubated with E. coli or P. aeruginosa. Bacterial killing activity; IL-1b and TLR4 protein expression; NF-kB DNA binding activity assay; as well as IL-1b, TNFa, TLR2, TLR4 and TLR9 mRNA expression of macrophages were examined. We found that alveolar macrophages and peritoneal macrophages of Nod22939iC mice but not WT mice or TLR4-/- mice demonstrated a significant increase of E. coli killing activity. Bacterial challenge also induced a significant increase of pro-IL-1b protein expression; NF-kB DNA binding activity; as well as IL-1b and TNFa mRNA expression of the peritoneal macrophages in Nod22939iC mice. Colletively, the increase of bacterial killing activity, IL-1b expression, and NF-kB DNA binding activity of macrophages in Nod22939iC mice suggests that NOD2 is a positive regulator of NF-kB/IL-1b-mediated innate response to bacteria challenge in Crohn’s disease. Nod22939iC also cause increased bacterial killing activity in macrophage of mice.
目錄


中文摘要 9
英文摘要 10
緒論
文獻回顧 1
第一章
介紹 11
第二章
方法 14
第三章
結果 18
第四章
討論 21

參考文獻 25

圖解 28

附錄 40
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