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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 朱清良 | |
| dc.contributor.author | Tzu-Shiuan Lin | en |
| dc.contributor.author | 林子暄 | zh_TW |
| dc.date.accessioned | 2021-05-19T17:44:18Z | - |
| dc.date.available | 2023-08-30 | |
| dc.date.available | 2021-05-19T17:44:18Z | - |
| dc.date.copyright | 2018-08-30 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-14 | |
| dc.identifier.citation | 1. Pardo-Camacho, C., et al., Epithelial immunity: priming defensive responses in the intestinal mucosa. Am J Physiol Gastrointest Liver Physiol, 2018: p. G247–G255.
2. Latiff, A.H.A. and M.A. Kerr, The clinical significance of immunoglobulin A deficiency. The Association for Clinical Biochemistry, 2007. 44: p. 131–139. 3. MW, R., et al., IgA antibody as a non-inflammatory regulator of immunity.Biochem Soc Trans., 1997. 25: p. 466–70. 4. Yel, L., Selective IgA Deficiency. J Clin Immunol, 2010. 30: p. 10-16. 5. Kaetzel, C.S., Cooperativity among secretory IgA, the polymericimmunoglobulin receptor, and the gut microbiota promotes host-microbial mutualism. Immunol Lett, 2014. 162: p. 10–21. 6. AE, H., B. PJ, and H. AB, Structural insights into antibody-mediated mucosal immunity. Curr Top Microbiol Immunol, Herr AB. 308: p. 173-204. 7. R, A., et al., Signature biomarkers in Crohn's disease: toward a molecular classification. Mucosal Immunol., 2008. 1: p. 399-411. 8. Phalipon, A. and B. Corthe´sy, Novel functions of the polymeric Ig receptor: well beyond transport of immunoglobulins. TRENDS in Immunology, 2003. 24. 9. Schneeman, T.A., et al., Regulation of the Polymeric Ig Receptor by Signaling 35 through TLRs 3 and 4: Linking Innate and Adaptive Immune Responses. The Journal of Immunology, 2005. 175: p. 376-384. 10. Schjerven, H., P. Brandtzaeg, and F.-E. Johansen, A Novel NF-kB/Rel Site in Intron 1 Cooperates with Proximal Promoter Elements to Mediate TNF-alpha-Induced Transcriptio of the Human Polymeric Ig Receptor. The Journal of Immunology, 2001. 11. Cao, A.T., et al., Th17 Cells Upregulate Polymeric Ig Receptor and Intestinal IgA and Contribute to Intestinal Homeostasis. The Journal of Immunology, 2012.189: p. 4666-4673. 12. Johansen, F.-E. and C. Kaetzel, Regulation of the polymeric immunoglobulin receptor and IgA transport: new advances in environmental factors that stimulate pIgR expression and its role in mucosal immunity Mucosal Immunol., 2011. 4(6). 13. Fujino, S., et al., Increased expression of interleukin 17 in inflammatory bowel disease. Gut, 2003. 52: p. 65–70. 14. SR, T., et al., A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Brodalumab in Patients With Moderate-to-Severe Crohn's Disease. Am J Gastroenterol, 2016. 111(11). 15. Kumar, P., et al., Intestinal interleukin-17 receptor signaling mediates reciprocal control of the gut microbiota and autoimmune inflammation.Immunity, 2016. 44: p. 659–671. 16. Wu, N.-L., et al., Syk Mediates IL-17-Induced CCL20 Expression by Targeting Act1-Dependent K63-Linked Ubiquitination of TRAF6. Journal of Investigative Dermatology, 2015. 135: p. 490–498. 17. MT, A., Toll-like receptor signaling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol., 2010. 10(2): p. 131-44. 18. Leppkes, M., et al., Pleiotropic functions of TNF-α in the regulation of the intestinal epithelial reponse to inflammation. International Immunology.International Immunology, 2014. 26(9): p. 509–515. 19. Schroder, K., et al., Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol, 2004. 75(2): p. 163-89. 20. MF, N., Cytokines in inflammatory bowel disease. Nat Rev Immunol., 2014.14(5): p. 329-42. 21. P., K., et al., Interferon-γ stimulation of messenger RNA for human secretory component(poly-Ig receptor) depends on continuous intermediate protein synthesis. Scand J. Immun., 1993. 37: p. 251-256. 22. JF, P., Y. KR, and P. KM, Transcriptional regulation of the human polymeric immunoglobulin receptor gene by interferon-γ. Molec Immunol, 1997. 34: p.75-91. 23. Mócsai, A., J. Ruland, and V.L.J. Tybulewicz, The SYK tyrosine kinase: a crucial player in diverse biological functions. NATuRe ReVIewS | Immunology, 2010. 10: p. 387-402. 24. Deng, G.-M., V.C. Kyttaris, and G.C. Tsokos, Targeting Syk in Autoimmune Rheumatic Diseases. Fronties in Immunology. 7(78). 25. Friedberg, J.W. and J. Sharman, Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood, 2010. 115(15): p. 2578-2858. 26. Duta, F., et al., Differential expression of spleen tyrosine kinase Syk isoforms in tissues: Effects of the microbial flora. Histochem Cell Biol 2006. 126(4): p. 495- 505. 27. G, C., et al., The Syk Inhibitor Fostamatinib Decreases the Severity of Colonic Mucosal Damage in a Rodent Model of Colitis. J Crohns Colitis, 2015. 9(10): p.907-17. 28. S, C.-K., et al., Human intestinal epithelial cells respond to β-glucans via Dectin-1 and Syk. Eur J Immunol, 2014. 12: p. 3729-40. 29. R, C.K., et al., Cell polarity regulates the release of secretory component, the epithelial receptor for polymeric immunoglobulins, from the surface of HT-29 colon carcinoma cells. 148, 1991: p. 35-47. 30. Blanch, V.J., J.F. Piskurich, and C.S. Kaetzel, Cutting edge: coordinate regulation of IFN regulatory factor-1 and the polymeric Ig receptor by proinflammatory cytokines. 162, 1999. 3: p. 1232-1235. 31. M.D., P.B.A., et al., T-cell cytokines affect mucosal immunoglobulin A transport. The American Journal of Surgery. 194(1): p. 128-133. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7468 | - |
| dc.description.abstract | 多聚免疫球蛋白受體 (polymeric immunoglobulin receptor, pIgR) 表現在腸道表皮細胞中，其對於維持腸道免疫系統的恆定扮演相當重要的角色，主要功能為協助免疫球蛋白 (Immunoglobulin A, IgA) 轉變成為分泌型免疫球蛋白(Secretory immunoglobulin A, sIgA)，並協助運送至腸道中，幫助維持腸道系統恆定。腸道表皮細胞會受到多種不同的刺激而增加多聚免疫球蛋白受體的表現，包含類鐸配體 (Toll-like receptor ligand)、介白素-17(Interleukin17, IL-17)、腫瘤壞死因子 (Tumor necrosis factor alpha, TNF-α)等等。
脾酪胺酸激酶 (Spleen tyrosine kinase, Syk) 在免疫細胞中已有許多研究指出其在訊號傳遞中扮演重要角色，但在腸道表皮細胞中的角色尚未有深入地探討。過去曾有報導指出，在以脾酪氨酸激酶抑制劑治療發炎性疾病時，會導致腹瀉的副作用。而脾酪胺酸激酶在免疫細胞以及部分非免疫細胞中會參與在介白素-17、腫瘤壞死因子、以及類鐸配體等之訊號傳遞過程，但在腸道表皮細胞上仍未有相關研究，因此本研究即是探討脾酪胺酸激酶是否可能會參與並影響在腸道表皮細胞中多聚免疫球蛋白受體的表現。 實驗中發現，在給予腸道表皮細胞介白素-17、腫瘤壞死因子-α 等的刺激之後，降低脾酪氨酸激酶會影響部分多聚免疫球蛋白受體的蛋白質的表現量。 | zh_TW |
| dc.description.abstract | Polymeric immunoglobulin receptor (pIgR) expressed in intestinal epithelial cells, which plays an essential role to maintain the homeostasis of the gut system. The main function of pIgR is to facilitate immunoglobulin A (IgA) transform to secretory immunoglobulin A (SIgA) and transport from lamina propria to lumen. Intestinal epithelial cells are regulated by different stimulations to upregulate the expression of pIgR, which included toll-like receptors (TLRs), interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α). Spleen tyrosine kinase (Syk)has been
reported to participate in different and abundant signaling transduction, but the role of Syk in intestinal epithelial cells remains unclear. Syk has been reported to participate in the signal transduction of IL-17, TLRs, and TNF in immune and nonimmune cells, however not on intestinal epithelia. Hence we hypothesized that Syk may participate and influence the expression of pIgR and affect the homeostasis of the gut system. In this study, we found that Syk may have participated in the regulation of pIgR expression, but need further experiment to confirm the effect of Syk in pIgR regulation. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-19T17:44:18Z (GMT). No. of bitstreams: 1 ntu-107-R05449008-1.pdf: 1071611 bytes, checksum: 7973e7fd32b826a7b8ee64fd3a641634 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 誌謝 i
中文摘要 ii Abstract iii 目錄 iv 一、背景介紹 (Introduction) 1 1.腸道免疫系統恆定的維持 1 2.腸道表皮細胞 (Intestinal epithelial cell, IEC) 1 3.免疫球蛋白A (Immunoglobulin A, IgA) 2 4.免疫球蛋白A 缺失 3 5.多聚免疫球蛋白受體 (polymeric immunoglobulin receptor, pIgR) 3 6.多聚免疫球蛋白受體的調控 4 6-1 介白素-17A (Interleukin-17A) 4 6-2 類鐸受體-3 (Toll-like receptor 3, TLR-3) 5 6-3 腫瘤壞死因子 (Tumor necrosis factor alpha, TNF-α) 5 6-4 干擾素-γ (Interferon-γ) 6 7.脾酪胺酸激酶 (Spleen tyrosine kinase, Syk) 6 8.脾酪胺酸激酶在腸道中的研究 7 二、研究動機 (Rationale) 8 三、材料與方法(Materials and methods) 9 1.細胞培養 9 1.1 使用細胞株以及相關試劑 9 1.2 細胞培養方式 9 2.降低脾酪胺酸激酶 (Syk) 在細胞中的表現 9 3.細胞蛋白萃取(Protein extraction)及西方墨點法(western blot) 10 3.1 細胞蛋白萃取 10 3.2 膠體製備 (SDS-PAGE preparation) 11 3.3 電泳 (Electrophoresis) 11 3.4 轉漬 (Transfer) 11 3.5 阻攔 (Blocking) 11 3.6 檢測 12 4. RNA 純化 (RNA extraction) 及核酸序列定量偵測系統(Real-time PCR) 13 5.分離小鼠腸道表皮細胞 14 5-1. Buffer 14 5.2 分離步驟 14 6. 統計分析方法 (Statistical analysis) 15 四、實驗結果 (Results) 16 1.探討在降低腸道表皮細胞上脾酪胺酸激酶的活性下，以介白素-17、腫瘤壞死因子-α、干擾素-γ 以及聚肌胞甘酸的刺激下，大腸表皮細胞株 (HT-29) 多聚免疫球蛋白受體表現量改變。 16 2.建立以Syk shRNA 轉染降低在人類大腸表皮細胞株(HT-29)中脾酪胺酸激酶之基因表現之系統 17 3.降低脾酪胺酸激酶基因表現的細胞株在未受到刺激的情況下，多聚免疫球蛋白受體的表現量在不同天數的培養情況下並無顯著差異。 17 4.比較在不同培養時間下，同樣給予介白素-17 的刺激後，降低脾酪胺酸激酶基因表現細胞株與控制組的多聚免疫球蛋白受體表現量提升的差異性。 18 5.在同樣給予腫瘤壞死因子-α 的刺激下，相較於控制組降低脾酪胺酸激酶基因表現細胞株的多聚免疫球蛋白受體表現量提升受到抑制。 18 6.在同樣給予干擾素-γ 的刺激下，比較於控制組降低脾酪胺酸激酶基因表現細胞株的多聚免疫球蛋白受體表現量。 19 7. 在同樣給予聚肌胞甘酸的刺激下，比較於控制組降低脾酪胺酸激酶基因表現細胞株的多聚免疫球蛋白受體表現量。 19 9.以西方墨點法確認在降低脾酪胺酸激酶的組別相比於控制組，多聚免疫球蛋白受體蛋白表現量的差異。 19 10.在腸道表皮細胞脾酪胺酸激酶基因敲除小鼠中分離出來的腸道表皮細胞，分析其腸道的多聚免疫球蛋白受體基因表現量。 20 五、討論 21 六、附圖 23 七、參考資料 (Reference) 34 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討 Syk 磷酸激酶在腸道表皮細胞中調控多聚免疫球蛋白受體之角色 | zh_TW |
| dc.title | Study the role of spleen tyrosine kinase(Syk)
in regulating polymeric immunoglobulin receptor(pIgR) expression in intestinal epithelial cell(IEC) | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 余佳慧,徐志文 | |
| dc.subject.keyword | 脾酪氨酸激?,腸道表皮細胞,多聚免疫球蛋白受體,介白素-17,腫瘤壞死因子-α,干擾素-γ,聚肌胞?酸, | zh_TW |
| dc.subject.keyword | spleen tyrosine kinase (Syk),intestinal epithelial cell (IEC),Polymeric immunoglobulin receptor (pIgR),Interleukin-17A(IL-17A),Interferon-gamma(IFN- γ),Tumor necrosis factor-α(TNF-α),Polyinosinic:polycytidylic acid (Poly I:C), | en |
| dc.relation.page | 38 | |
| dc.identifier.doi | 10.6342/NTU201803361 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2018-08-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| dc.date.embargo-lift | 2023-08-30 | - |
| 顯示於系所單位： | 免疫學研究所 | |
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