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研究生:鄭貴云
研究生(外文):Guei-Yun Cheng
論文名稱:半乳糖凝集素-3與介白素-22訊號傳遞對於腸表皮細胞表現抗菌胜肽之影響
論文名稱(外文):The Effect of Galectin-3 and IL-22 Signaling on Antimicrobial Peptides Gene Expression in Intestinal Epithelial Cells
指導教授:朱清良
指導教授(外文):Ching-Liang Chu
口試日期:2017-07-24
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:免疫學研究所
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:2017
畢業學年度:105
語文別:中文
論文頁數:39
中文關鍵詞:半乳糖凝集素-3介白素-22炎症性腸病抗菌胜肽Reg3bReg3gS100A8S100A9
外文關鍵詞:galectin-3Interleukin-22nflammatory bowel diseaseantimicrobial peptidesReg3bReg3gS100A8S100A9
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Galectin-3 (Gal-3) 在生理反應上調控許多生物活性功能。在腸炎症患者中,腸道中的Gal-3 表現量明顯較健康人低。在腸道發炎情況下,Interleukin-22 (IL-22) 能透過表現抗菌蛋白,如Reg3β/3γ 及 S100A8/A9,來保護腸道避免遭受病原菌侵犯。IL-22結合到IL-22受器後,會活化下游Jak1/Tyk2-STAT3、Akt 及 MAPK 訊號路徑。許多研究顯示 Gal-3 及 IL-22 對於維持腸道生理平衡扮演重要角色,故我們假設 Gal-3 也許參與在IL-22/IL-22R 訊號傳遞,並調控腸表皮細胞的功能。我們研究中發現,Gal-3似乎不參與在IL-22/IL-22R下游主要的三條訊號路徑。在動物實驗的大腸組織中,雖然Gal-3不參與在調控 Reg3b/3g 的表現,但Gal-3會負調控 IL-22 所誘導表現的 S100A8/A9。
Galectin-3 (Gal-3) is known to exert a lot of biological function. Expression of Gal-3 is significantly downregulated in the gut of patients with inflammatory bowel disease (IBD). Interleukin-22 (IL-22) is known to protect against colitis through enhancing the production of antimicrobial peptides (AMP), such as Reg3β/3γ and S100A8/A9. Binding of IL-22 to its receptor activates Jak1/Tyk2-STAT3, Akt and MAPK signaling pathways. It has been reported that Gal-3 and IL-22 are important to maintain the intestinal homeostasis. We hypothesize that Gal-3 may participate in IL-22 signaling and regulate the functions in intestinal epithelial cells (IECs). In our study, Gal-3 seems not regulate the three major IL-22 signaling pathways. Although Gal-3 is not involved in regulating Reg3b/3g expression, it negatively regulates IL-22-induced S100A8/A9 expression in colon.
致謝 I
中文摘要 III
Abstract IV
一、 前言 1
1. Inflammatory bowel disease (IBD) 1
2. Galectin (Gal) 2
2.1 Galectins 簡介 2
表一、Galectins 依結構分類 2
表二、Galectins 在人類與小鼠的分布情形 2
2.2 Galectin-3 (Gal-3) 3
3. Interleukin-22 (IL-22) 4
4. 抗菌蛋白 (antimicrobial peptides/proteins, AMPs) 5
4.1 Reg3β/3γ 5
4.2 S100A8/A9 5
二、材料與方法 7
1. 細胞培養 7
1.1 CMT-93 (Mouse intestinal epithelial cell line) 7
1.2 HT-29 (human intestinal epithelial cell line) 7
2. 動物實驗 7
2.1 操作與培養步驟 7
2.2 組織處理配方 8
3. Knockdown 8
4. Real-time PCR 9
5. 西方墨點法 (Western Blotting) 9
6. 統計分析 10
三、結果 11
1. Galectin-3 普遍表現在 IEC 11
2. 細胞生長密度不影響 galectins profile 11
3. IL-22 不影響腸表皮細胞galectins 的表現分布 11
4. Gal-3 也許不參與在IL-22 所誘導的 AMPs之表現 in vitro 12
5. Gal-3 不影響 IL-22/IL-22R axis 的主要訊號傳遞 13
6. Gal-3 會影響 IL-22Ra1 的表現 ex vivo 13
7. Gal-3缺失不影響 IL-22 所誘導的 Reg3β/γ 之表現 ex vivo 14
8. Gal-3 缺失會促進IL-22 所誘導的 S100A8/A9 之表現 in vivo 14
四、討論 15
五、圖表 18
六、參考文獻 29
七、附件 i
附件一:名稱縮寫 i
附件二:Lgals3 shRNA sequence ii
1. Mouse ii
2. Human ii
附件三:試劑 iv
附件四:Real-time PCR Primers v
1. Mouse v
2. Human vi
附件五:實驗動物鼠品系與資訊 vii
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