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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 朱清良(Ching-Liang Chu) | |
| dc.contributor.author | Wei-Ting Liao | en |
| dc.contributor.author | 廖偉廷 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:39:37Z | - |
| dc.date.available | 2020-09-08 | |
| dc.date.copyright | 2017-09-08 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-07-30 | |
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J. et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. The Journal of clinical investigation 113, 1490-1497, (2004). 25 Sturm, A. Dignass, A. U. Epithelial restitution and wound healing in inflammatory bowel disease. World journal of gastroenterology 14, 348-353 (2008). 26 Saleh, M. Trinchieri, G. Innate immune mechanisms of colitis and colitis-associated colorectal cancer. Nature reviews. Immunology 11, 9-20, (2011). 27 Ostanin, D. V. et al. T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade. American journal of physiology. Gastrointestinal and liver physiology 296, G135-146, (2009). 28 Bhan, A. K., Mizoguchi, E., Smith, R. N. Mizoguchi, A. Spontaneous chronic colitis in TCR alpha-mutant mice; an experimental model of human ulcerative colitis. International reviews of immunology 19, 123-138 (2000). 29 Keubler, L. M., Buettner, M., Hager, C. Bleich, A. A Multihit Model: Colitis Lessons from the Interleukin-10-deficient Mouse. Inflammatory bowel diseases 21, 1967-1975, (2015). 30 Antoniou, E. et al. The TNBS-induced colitis animal model: An overview. Annals of medicine and surgery (2012) 11, 9-15, (2016). 31 Chassaing, B., Aitken, J. D., Malleshappa, M. Vijay-Kumar, M. Dextran sulfate sodium (DSS)-induced colitis in mice. Current protocols in immunology 104, Unit 15.25., (2014). 32 Sabat, R., Ouyang, W. Wolk, K. Therapeutic opportunities of the IL-22-IL-22R1 system. Nature reviews. Drug discovery 13, 21-38, (2014). 33 Pickert, G. et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. The Journal of experimental medicine 206, 1465-1472, (2009). 34 Hainzl, E. et al. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis. Journal of immunology (Baltimore, Md. : 1950) 195, 5011-5024, (2015). 35 Mitra, A., Raychaudhuri, S. K. Raychaudhuri, S. P. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67600 | - |
| dc.description.abstract | 脾酪氨酸激酶(spleen tyrosin kinase, Syk)在免疫細胞中的功能及表現已被廣泛研究，其中發現Syk參與許多細胞活化或是免疫反應的訊息傳遞路徑．也有一些研究指出Syk也存在於非免疫細胞中，但有關它在腸道表皮細胞中的角色及功能都還不清楚．腸道表皮細胞在維持腸道系統恆定中扮演重要的角色，若其功能異常可能導致發炎性腸道疾病(inflammatory bowel disease, IBD)．先前的研究發現在腸道表皮細胞專一性剔除Syk的小鼠（SykΔIEC）經葡聚糖硫酸鈉(dextran sulfate sodium, DSS)引發腸炎後，其發炎情形較野生型(WT)嚴重，似乎Syk在腸道表皮細胞中具有保護的功能．因此我們假設Syk參與腸道表皮細胞中的某種訊息傳遞路徑，因而影響表皮細胞的功能．根據先前的文獻指出介白素-22（Interleukin-22, IL-22）可促進腸道表皮細胞產生抗微生物胜肽(antimicrobial peptides, AMPs)及黏液蛋白(mucin)，進而減緩腸炎的情形; 而IL-22的訊息傳遞方式主要是經由活化JAK1/3-STAT3來調控細胞反應．因此我們將研究Syk是否參與在IL-22的訊息傳遞中．此篇研究我們探討Syk的確參與在IL-22-STAT3的訊息傳遞中，並可幫助腸道表皮細胞產生抗微生物胜肽及黏液蛋白，幫助維持腸道系統的恆定． | zh_TW |
| dc.description.abstract | Spleen tyrosin kinase (Syk) is widely expressed in hematopoietic cells and regulates many immune responses. While Syk is also expressed in non- hematopoietic cells, the role of Syk in intestinal epithelial cells (IECs) is still elusive. IECs play an important role in maintaining mucosal homeostasis, so dysregulation of IECs causes the development of inflammatory Bowel disease (IBD). In previous study, we have demonstrated that IEC-specific Syk-deficient (SykΔIEC) mice are more sensitive to dextran sodium sulfate (DSS)-induced colitis compared to normal mice. Thus, we hypothesize that Syk may be involved in a protective signal in IECs. According to literature, interleukin 22 (IL-22) is known to reduce colitis through enhancing the production of antimicrobial peptides (AMPs) and mucin by IECs. These functions are mediated by activations of STAT3 and some kinases. In this study, we found that Syk may play a positive role in IL-22-STAT3 pathway and promoted secretion of AMPs and mucin in order to maintain gut homeostasis . | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:39:37Z (GMT). No. of bitstreams: 1 ntu-106-R04449004-1.pdf: 2992477 bytes, checksum: 9807265d083403e6592da083871c138e (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 中文摘要 ........................................................................................................................ i Abstract ........................................................................................................................ ii 目錄 .............................................................................................................................. iii 圖表目錄 ....................................................................................................................... v 一、背景介紹 (introduction) ..................................................................................... 1 1. 脾酪氨酸激脢（spleen tyrosin kinase, Syk） .................................................. 1 2. 腸道表皮細胞及腸道恆定 .................................................................................. 2 3. 發炎性腸道疾病(Inflammatory bowel disease) ............................................... 3 4. 腸道中IL-22 IL-22R1 系統 ............................................................................... 4 二、研究動機 (Rationale) .......................................................................................... 6 三、材料及方法 (Materials and methods) ............................................................... 8 1. 細胞培養及相關實驗 ........................................................................................ 8 1.1 細胞株及試劑： ................................................................................................ 8 1.2 培養方式： ......................................................................................................... 8 2. 細胞生存試驗（Cell viability assay） .............................................................. 9 3. 降低脾酪氨酸激脢(Syk)在細胞中的表現 ......................................................... 9 4. 細胞蛋白萃取(Protein Extraction)及西方墨點法（Western blot analysis）10 5. RNA 純化 (RNA extraction)及核酸序列定量偵測系統 (Real-time PCR) . 12 6. 實驗動物 ............................................................................................................ 13 7. 分離小鼠腸道表皮細胞 .................................................................................... 14 四、研究目標 (Aims) ................................................................................................ 16 五、實驗結果 ............................................................................................................. 18 1. 脾酪氨酸激脢（Syk）確實有參與在IL-22 的訊息傳遞路徑中 .................. 18 2. IL-22 可增加腸道表皮細胞株抗微生物胜肽mRNA 之表現，並且磷酸化下游 相關訊息傳遞蛋白 ................................................................................................. 18 3. 人類腸道表皮細胞中建立脾酪氨酸激脢降低（knockdown）之系統並再次驗 證脾酪氨酸激脢（Syk）確實參與在IL-22 的訊息傳遞路徑中 ....................... 19 4. 分離小鼠腸道表皮細胞之效率 ........................................................................ 19 5. 比較一般小鼠（wild-type, WT）和腸道專一性剔除脾酪氨酸激脢小鼠(SykΔIEC) 分離之表皮細胞，經IL-22 後刺激後，其下游相關基因及訊息傳遞蛋白之變化 ................................................................................................................................. 20 六、討論 ..................................................................................................................... 22 七、附圖 ..................................................................................................................... 24 | |
| dc.language.iso | zh-TW | |
| dc.subject | 黏液蛋白 | zh_TW |
| dc.subject | 介白素-22 | zh_TW |
| dc.subject | 抗微生物胜? | zh_TW |
| dc.subject | 腸道表皮細胞 | zh_TW |
| dc.subject | 腸炎 | zh_TW |
| dc.subject | 脾酪氨酸激? | zh_TW |
| dc.subject | mucin | en |
| dc.subject | antimicrobial peptisdes (AMPs) | en |
| dc.subject | Interleukin 22 (IL-22) | en |
| dc.subject | inflammatory bowel disease (IBD) | en |
| dc.subject | intestinal epithelial cell | en |
| dc.subject | spleen tyrosin kinase (Syk) | en |
| dc.title | 探討Syk 在腸道表皮細胞中的介白素-22 訊息傳遞及功 能之角色 | zh_TW |
| dc.title | The role of Syk in IL-22 signaling and function in the intestinal epithelial cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 余佳慧(Chia-Hui Yu),廖南詩(Nan-Shih Liao) | |
| dc.subject.keyword | 脾酪氨酸激?,腸道表皮細胞,腸炎,介白素-22,抗微生物胜?,黏液蛋白, | zh_TW |
| dc.subject.keyword | spleen tyrosin kinase (Syk),intestinal epithelial cell,inflammatory bowel disease (IBD),Interleukin 22 (IL-22),antimicrobial peptisdes (AMPs),mucin, | en |
| dc.relation.page | 34 | |
| dc.identifier.doi | 10.6342/NTU201702129 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-07-31 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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