請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49909完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 謝松洲(Song-Chou Hsieh) | |
| dc.contributor.author | Hui-Ching Hsu | en |
| dc.contributor.author | 許惠晴 | zh_TW |
| dc.date.accessioned | 2021-06-15T12:26:02Z | - |
| dc.date.available | 2019-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-10 | |
| dc.identifier.citation | 1. Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature. 2011;469(7330):323-35.
2. Zhou XJ, Zhang H. Autophagy in immunity: implications in etiology of autoimmune/autoinflammatory diseases. Autophagy. 2012;8(9):1286-99. 3. Maes H, Rubio N, Garg AD, Agostinis P. Autophagy: shaping the tumor microenvironment and therapeutic response. Trends Mol Med. 2013;19(7):428-46. 4. Gianchecchi E, Delfino DV, Fierabracci A. Recent insights on the putative role of autophagy in autoimmune diseases. Autoimmun Rev. 2014;13(3):231-41. 5. Pierdominici M, Vomero M, Barbati C, Colasanti T, Maselli A, Vacirca D, et al. Role of autophagy in immunity and autoimmunity, with a special focus on systemic lupus erythematosus. FASEB J. 2012;26(4):1400-12. 6. Bhattacharya A, Eissa NT. Autophagy and autoimmunity crosstalks. Front Immunol. 2013;4:88. 7. Deretic V. Multiple regulatory and effector roles of autophagy in immunity. Curr Opin Immunol. 2009;21(1):53-62. 8. Deretic V, Levine B. Autophagy, immunity, and microbial adaptations. Cell Host Microbe. 2009;5(6):527-49. 9. Puleston DJ, Simon AK. Autophagy in the immune system. Immunology. 2014;141(1):1-8. 10. Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan RN, et al. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell. 2007;128(5):931-46. 11. Martinez J AJ, Oberst A, Ness R, Dilloa CP, Fitzgerald P,, Hengartner MO aGD. Microtubule-associated protein 1 light chain 3 alpha(LC3)-associated phagocytosis is required for the efficient clearance of dead cells. PNAS. 2011;108(No. 42):17396-401. 12. Sanjuan MA, Dillon CP, Tait SW, Moshiach S, Dorsey F, Connell S, et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007;450(7173):1253-7. 13. Rogers NJ, Lees MJ, Gabriel L, Maniati E, Rose SJ, Potter PK, et al. A defect in Marco expression contributes to systemic lupus erythematosus development via failure to clear apoptotic cells. J Immunol. 2009;182(4):1982-90. 14. Majai G, Kiss E, Tarr T, Zahuczky G, Hartman Z, Szegedi G, et al. Decreased apopto-phagocytic gene expression in the macrophages of systemic lupus erythematosus patients. Lupus. 2014;23(2):133-45. 15. Munoz LE, Janko C, Schulze C, Schorn C, Sarter K, Schett G, et al. Autoimmunity and chronic inflammation - two clearance-related steps in the etiopathogenesis of SLE. Autoimmun Rev. 2010;10(1):38-42. 16. Liu Z, Davidson A. Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med. 2012;18(6):871-82. 17. Harley JB, Alarcon-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008;40(2):204-10. 18. Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, et al. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet. 2009;41(11):1228-33. 19. Zhou XJ, Lu XL, Lv JC, Yang HZ, Qin LX, Zhao MH, et al. Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis. 2011;70(7):1330-7. 20. Hartleben B, Godel M, Meyer-Schwesinger C, Liu S, Ulrich T, Kobler S, et al. Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. J Clin Invest. 2010;120(4):1084-96. 21. Mohan C, Putterman C. Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis. Nat Rev Nephrol. 2015;11(6):329-41. 22. Perl DFaA. mTOR Signaling: A Central Pathway to Pathogenesis in Systemic Lupus Erythematosus? Discovery Medicine. 2010;March; 9(46):173-8. 23. Sauer S, Bruno L, Hertweck A, Finlay D, Leleu M, Spivakov M, et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci U S A. 2008;105(22):7797-802. 24. Valencia X, Yarboro C, Illei G, Lipsky PE. Deficient CD4+CD25high T Regulatory Cell Function in Patients with Active Systemic Lupus Erythematosus. The Journal of Immunology. 2007;178(4):2579-88. 25. Gros F, Arnold J, Page N, Decossas M, Korganow AS, Martin T, et al. Macroautophagy is deregulated in murine and human lupus T lymphocytes. Autophagy. 2012;8(7):1113-23. 26. Alessandri C, Barbati C, Vacirca D, Piscopo P, Confaloni A, Sanchez M, et al. T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy. FASEB J. 2012;26(11):4722-32. 27. Clarke AJ, Ellinghaus U, Cortini A, Stranks A, Simon AK, Botto M, et al. Autophagy is activated in systemic lupus erythematosus and required for plasmablast development. Ann Rheum Dis. 2015;74(5):912-20. 28. Page N, Gros F, Schall N, Decossas M, Bagnard D, Briand JP, et al. HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus. Ann Rheum Dis. 2011;70(5):837-43. 29. Daniel J. Klionsky FCA, Hagai Abeliovich,. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8(4):445-544. 30. Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy. 2014;7(3):279-96. 31. Li B YY, Dong C, Shi Y and Xiong S. Blockade of macrophage autophagy ameliorates activated lymphocytes-derived DNA induced murine lupus possibly via inhibition of proinflammatory cytokine production. Clinical and Experimental Rheumatology. 2014;32:705-14. 32. Eng M. Tan ASC, James F. Fries, Alfonse T. Masi, Dennis J. McShane, Naomi F. Rothfield, Jane Green Schaller, Norman Talal and Robert J. Winchester. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25(No. 11 (November 1982)):1271-7. 33. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell. 2010;140(3):313-26. 34. Gillian S Dean JT-P, Esther Crawley, David A Isenberg. Cytokines and systemic lupus erythematosus. Ann Rheum Dis. 2000;59:243-51. 35. E Tackey PLaGI. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 2004;13:339-43. 36. Illei GG, Tackey E, Lapteva L, Lipsky PE. Biomarkers in systemic lupus erythematosus: II. Markers of disease activity. Arthritis Rheum. 2004;50(7):2048-65. 37. Shirota Y, Yarboro C, Fischer R, Pham TH, Lipsky P, Illei GG. Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus. Ann Rheum Dis. 2013;72(1):118-28. 38. Finck BK CB, Wofsy D. Interleukin 6 promotes murine lupus in NZB/NZW F1 mice. The Journal of Clinical Investigation. 1994;94(2):585-91. 39. Mihara M TN, Takeda Y, and Ohsugi Y. IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W F1 mice. Clinical and Experimental Immunology. 1998;112(3):397-402. 40. Jain S, Park G, Sproule TJ, Christianson GJ, Leeth CM, Wang H, et al. Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB.Yaa Mice. PLoS One. 2016;11(4):e0153059. 41. Birner P, Heider S, Petzelbauer P, Wolf P, Kornauth C, Kuroll M, et al. Interleukin-6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus. Exp Dermatol. 2016;25(4):305-10. 42. Robak E, Sysa-Jedrzejewska A, Dziankowska B, Torzecka D, Chojnowski K, Robak T. Association of interferon gamma, tumor necrosis factor alpha and interleukin 6 serum levels with systemic lupus erythematosus activity. Archivum immunologiae et therapiae experimentalis. 1998;46(6):375-80. 43. Sabry A, Sheashaa H, El-Husseini A, Mahmoud K, Eldahshan KF, George SK, et al. Proinflammatory cytokines (TNF-alpha and IL-6) in Egyptian patients with SLE: its correlation with disease activity. Cytokine. 2006;35(3-4):148-53. 44. Cigni A, Pileri PV, Faedda R, Gallo P, Sini A, Satta AE, et al. Interleukin 1, interleukin 6, interleukin 10, and tumor necrosis factor alpha in active and quiescent systemic lupus erythematosus. J Investig Med. 2014;62(5):825-9. 45. Sabry A, Elbasyouni SR, Sheashaa HA, Alhusseini AA, Mahmoud K, George SK, et al. Correlation between levels of TNF-alpha and IL-6 and hematological involvement in SLE Egyptian patients with lupus nephritis. Int Urol Nephrol. 2006;38(3-4):731-7. 46. Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, et al. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007;27(5):461-6. 47. Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, et al. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 2010;62(2):542-52. 48. Gabay C CN, Moral F, Roux-Lombard P, Meyer O, Dayer JM, Vischer T, Yazici H, Guerne PA. Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. J Rheumatol. 1997;24(2):303-8. 49. Herrera-Esparza R B-CO, Villalobos-Hurtado R and Avalos-Diaz E. Renal expression of IL-6 and TNF-alpha genes in lupus nephritis. Lupus. 1998;7:154-8. 50. Ronnblom L, Alm GV, Eloranta ML. The type I interferon system in the development of lupus. Semin Immunol. 2011;23(2):113-21. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49909 | - |
| dc.description.abstract | 背景：自噬作用是細胞分解自身細胞內的組成物以達到恆定的過程。自噬作用原先被視為是體內為了適應環境中營養缺乏的狀況而進行自我回收、再利用物質的機制，近年發現其在免疫以及發炎反應都佔有重要角色。細胞凋亡時，死亡細胞的清除及抗原呈現之異常，可能和自噬作用之異常有關，且可能與全身性紅斑狼瘡之致病機轉相關。細胞凋亡時，細胞核之蛋白質在分解的過程中會重新分配在細胞表面。在正常的生理狀況，這些蛋白質因巨噬細胞之迅速清除而不會引起自體免疫反應。因此巨噬細胞的功能異常，無法迅速清除自體抗原，也跟全身性紅斑狼瘡相關。第六介白質是一具有多重功能的細胞激素，可調控發炎反應，且可誘發B細胞成熟成漿細胞，在全身性紅斑狼瘡之致病機轉佔重要角色。巨噬細胞自噬作用與全身性紅斑狼瘡之致病機轉的關連現在仍不清楚。本研究探討第六介白質對於巨噬細胞自噬作用之影響。
實驗方法：THP-1細胞株衍生之巨噬細胞以及人類單核球衍生之巨噬細胞加入第六介白質或是第六介白質之受體阻抗劑培養。其自噬作用之功能由西方墨點法偵測LC3-II轉換試驗以及p62的量來衡量。 結果：由THP-1細胞株衍生之巨噬細胞上可見LC 3-II以及p62均升高，由此推論第六介白質抑制了正常的自噬作用。在使用rapamycin作為自噬作用之陽性對照組，亦呈現同樣結果。若預先加入第六介白質之受體阻抗劑，則可以抑制第六介白質對於巨噬細胞自噬作用的影響。使用人類單核球衍生之巨噬細胞進行實驗亦可以看到相似的結果。一個以關節炎以及尿中白血球增加為表現的全身性紅斑狼瘡病人其單核球衍生之巨噬細胞亦呈現自噬作用的缺陷。我們將進而探討第六介白質在全身性紅斑狼瘡對於巨噬細胞自噬作用的影響。 | zh_TW |
| dc.description.abstract | Background: Autophagy is a condition by which cells break down their own components to maintain homeostasis. Autophagy, initially viewed as a bulk-degradation mechanism in adaption to harsh environment, has been found to play a crucial role in immunity and inflammation. It has been proposed that defect in clearance of apoptotic cell debris and aberrant antigen presentation might be the link between autophagy and systemic lupus erythematosus (SLE). During apoptosis, nuclear proteins can be modified and redistributed on the cell surface. Under physiological conditions, these proteins are rapidly removed by macrophages and do not induce any autoimmunity. Therefore impaired macrophage function is also implicated in SLE. Interleukin-6 (IL-6) is a multifunctional cytokine, which plays a critical role in B cell hyperactivity and immunopathology of human SLE. The connection between impaired macrophage autophagy and SLE pathogenesis remains unclear. Here, we investigate the role of IL-6 in autophagy of macrophage.
Methods: THP-1 cell line derived macrophages and primary human monocyte-derived macrophages were treated with IL-6 and IL-6 receptor antagonist (IL-6 RA). We detected autophagy function by LC3-II turnover assay and p62 level using Western blots. Results: Impaired autophagy of THP-1 macrophages after IL-6 treatment was demonstrated by elevated LC3-II and p62 on Western blots. Using rapamycin as positive control of autophagy, the results were consistent. After pre-treatment with IL-6 receptor antagonist, the effects of IL-6 on macrophage autophagy can be reversed. Similar results were seen on primary human monocyte-derived macrophages. Monocyte-derived macrophages of a SLE patient with arthritis and pyuria also showed impaired autophagy. The role of IL-6 in macrophage autophagy in SLE will be discussed. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T12:26:02Z (GMT). No. of bitstreams: 1 ntu-105-P03421017-1.pdf: 2105355 bytes, checksum: 6bd3ed707ec42e4e0bb3956610072b9b (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 目 錄
口試委員會審定書 i 誌謝 ii 中文摘要 iii 英文摘要 iv 碩士論文內容 第一章 緒論 1.1 Overview of autophagy 1 1.2 Cytokines involved in autophagy 2 1.3 Role of macrophage in autophagy and autoimmune disease 3 1.4 Autophagy and systemic lupus erythematosus 4 1.5 Markers for autophagy 5 1.6 The connection between macrophage autophagy and pathogenesis of systemic lupus erythematosus 7 第二章 研究方法與材料 2.1 THP-1 cell culture 9 2.2 Cell treatment 9 2.3 Preparation of human monocyte-derived macrophages 9 2.4 Monocyte-derived macrophages treatment 10 2.5 Preparation of monocyte-derived macrophages of SLE patients and controls 10 2.6 Western blot analyses 11 2.7 Fluorescence microscopy to detect autophagosomes 11 2.8 Statistical analysis 12 第三章 結果 第一部份 13 3.1.1 Interleukin-6 induced autophagy in THP-1 macrophages 3.1.2 Interleukin-6 receptor antagonist reverses interleukin-6 effect on autophagy of THP-1 macrophages 3.1.3 Signaling pathway 第二部份 14 3.2 Tumor necrosis factor- and interferon-2b induced autophagy in THP-1 macrophages 第三部份 15 3.3 Fluorescence microscopy to detect LC3 and p62 on autophagosomes 第四部份 15 3.4 Interleukin-6 induced autophagy in human monocyte-derived macrophages 第五部份 16 3.5 Endogenous autophagy of macrophages in healthy control and systemic lupus erythematosus patients 第四章 討論 17 第五章 展望 22 第六章 參考文獻 23 第七章 圖表 27 第八章 附錄 52 | |
| dc.language.iso | en | |
| dc.subject | 第六介白質 | zh_TW |
| dc.subject | 自噬作用 | zh_TW |
| dc.subject | 巨噬細胞 | zh_TW |
| dc.subject | 全身性紅斑狼瘡 | zh_TW |
| dc.subject | Autophagy | en |
| dc.subject | IL-6 | en |
| dc.subject | systemic lupus erythematosus | en |
| dc.subject | macrophages | en |
| dc.title | 受第六介白質抑制之巨噬細胞自噬作用在全身性紅斑狼瘡之意義 | zh_TW |
| dc.title | Impaired Macrophage Autophagy Exerted by Interleukin-6 and its Implication in Systemic Lupus Erythematosus | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡長祐(Chang-Youh Tsai),楊宏志(Hung-Chih Yang) | |
| dc.subject.keyword | 自噬作用,巨噬細胞,全身性紅斑狼瘡,第六介白質, | zh_TW |
| dc.subject.keyword | Autophagy,macrophages,systemic lupus erythematosus,IL-6, | en |
| dc.relation.page | 52 | |
| dc.identifier.doi | 10.6342/NTU201602030 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-105-1.pdf 未授權公開取用 | 2.06 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。