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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 丁詩同(Shih-Torng Ding) | |
| dc.contributor.author | Yu-Ju Peng | en |
| dc.contributor.author | 彭裕如 | zh_TW |
| dc.date.accessioned | 2021-06-17T06:01:56Z | - |
| dc.date.available | 2019-02-14 | |
| dc.date.copyright | 2019-02-14 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-01-31 | |
| dc.identifier.citation | Acarturk, G., Acay, A., Demir, K., Ulu, M.S., Ahsen, A., and Yuksel, S. (2015). Neutrophil-to-lymphocyte ratio in inflammatory bowel disease - As a new predictor of disease severity. Bratisl Med J 116, 213-217.
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Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease. Inflamm Bowel Dis 16, 630-637. Wera, O., Lancellotti, P., and Oury, C. (2016). The Dual Role of Neutrophils in Inflammatory Bowel Diseases. J Clin Med 5, 118-141. Xu, X., Jackson, P.L., Tanner, S., Hardison, M.T., Roda, M.A., Blalock, J.E., and Gaggar, A. (2011). A self-propagating matrix metalloprotease-9 (MMP-9) dependent cycle of chronic neutrophilic inflammation. PLos One 6, 15781-15793. Yamamoto, K., Kiyohara, T., Murayama, Y., Kihara, S., Okamoto, Y., Funahashi, T., Ito, T., Nezu, R., Tsutsui, S., Miyagawa, J.I., et al. (2005). Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease. Gut 54, 789-796. Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003). Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423, 762-769. Yoda-Murakami, M., Taniguchi, M., Takahashi, K., Kawamata, S., Saito, K., Choi-Miura, N.H., and Tomita, M. (2001). Change in expression of GBP28/adiponectin in carbon tetrachloride-administrated mouse liver. Biochem Biophys Res Commun 285, 372-377. Zhang, B., Berger, J., Hu, E.I., Szalkowski, D., WhiteCarrington, S., Spiegelman, B.M., and Moller, D.E. (1996). Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha. Mol Endocrinol 10, 1457-1466. Zhang, R., Ito, S., Nishio, N., Cheng, Z., Suzuki, H., and Isobe, K. (2011). Up-regulation of Gr1+CD11b+ population in spleen of dextran sulfate sodium administered mice works to repair colitis. Inflamm Allergy Drug Targets 10, 39-46. Zhou, G.X., and Liu, Z. (2017). Potential roles of neutrophils in regulating intestinal mucosal inflammation of inflammatory bowel disease. J Dig Di 18,495-503. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71500 | - |
| dc.description.abstract | 脂肪細胞最為人熟知的功能為透過三酸甘油脂的合成和分解來調控能量平衡，近年來的研究亦發現脂肪細胞具有內分泌功能，產生脂肪激素調節不同的生理功能。脂聯素是種脂肪細胞激素，有調控生物體能量平衡和抗發炎的功用。然而，脂聯素和其接受體在腸道發炎扮演的角色卻是有爭議之處，且對嗜中性免疫細胞的影響仍是未知。故本次研究希望釐清脂聯素一型接受體對腸炎和嗜中性免疫細胞的影響。首先以化學藥劑葡聚糖硫酸引起脂聯素一型接受體轉殖基因小鼠產生急性腸炎，並以脂聯素重組蛋白處理腸道上皮細胞株和巨噬細胞株。實驗結果顯示，脂聯素一型接受體轉殖基因小鼠會罹患較嚴重的急性腸炎，且脂聯素重組蛋白會促進腸道上皮細胞和巨噬細胞表現發炎因子。在無誘導急性腸炎的轉殖基因小鼠腸道有較高量的發炎因子環氧合酶2和嗜中性免疫細胞驅化因子 (neutrophil chemokines, CXCL1，CXCL2和CXCL5)表現，且腸道有較多的嗜中性免疫細胞浸潤。本研究結果顯示脂聯素和其一型接受體可能會藉由兩種方式惡化腸道發炎: 1. 脂聯素和其一型接受體訊號會促進發炎因子的表現。2. 脂聯素一型接受體增加嗜中性免疫細胞驅化因子，造成腸道過量的嗜中性免疫細胞浸潤，過度活化的免疫反應造成嚴重的腸道發炎。 | zh_TW |
| dc.description.abstract | Adiponectin (ADN) is an adipokine mainly derived from adipose tissue. It binds to adiponectin receptor 1 and 2 (AdipoR1 and R2) to exert its function in regulating whole-body energy homeostasis and inflammatory responses. However, the role of ADN-AdipoR1 signaling in intestinal inflammation is controversial, and its role in the regulation of neutrophils is still unclear. Our goal was to clarify the role of AdipoR1 signaling in colitis and the effects on neutrophils.
We generated porcine AdipoR1 transgenic mice (pAdipoR1 mice) and induced murine colitis using dextran sulfate sodium (DSS) to study the potential role of AdipoR1 in inflammatory bowel disease. THP-1 macrophage and HT-29 colon epithelial cells were treated with ADN recombinant protein to study the effects of ADN expression on inflammation. After inducing murine colitis, pAdipoR1 mice developed more severe pathogenesis than wild-type (WT) mice. Treatment with ADN increased the expression of pro-inflammatory factors in THP-1 and HT-29 cells in association with the increased expression of cyclooxygenase2 (cox2), neutrophil chemokines (CXCL1, CXCL2 and CXCL5), and the infiltration of neutrophils were increased in the colon of pAdipoR1 mice. Current study showed that AdipoR1 signaling exacerbated colonic inflammation through two possible mechanisms. First, ADN-AdipoR1 signaling increased pro-inflammatory factors. Second, AdipoR1 enhanced neutrophil chemokine expression and neutrophils infiltration into the colonic tissue to increase inflammation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T06:01:56Z (GMT). No. of bitstreams: 1 ntu-108-D98626001-1.pdf: 3252214 bytes, checksum: 3641dd1ca81927159c04b7c1e9a62ffd (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 目錄
序言 ................................................................I 中文摘要 ...........................................................II Abstract ............................................................III Chapter 1. Literature review .......................................................................................1 1.1 Adiponectin ....................................................................................................1 1.1.1 Adiponectin .........................................................................................1 1.1.2 Transcriptional Regulation of Adiponectin ..........................................1 1.1.3 Regulation of Adiponectin Multimerization and Secretion ..................2 1.1.4 The Activation of Adiponectin ..............................................................3 1.2 Inflammatory Bowel Disease (IBD) ...............................................................4 1.2.1 Inflammatory Bowel Disease (IBD) ......................................................4 1.2.2 Current Therapies for Inflammatory Bowel Disease .............................5 1.2.3 Neutrophils and Mucosal Immunity .......................................................6 1.2.4 Neutrophils and Inflammatory Bowel Disease .......................................8 Chapter 2. Adiponectin and adiponectin receptor 1 overexpression enhances inflammatory bowel disease ....................................................................................12 2.1 Introduction ........................................................................................................12 2.2 Materials and Methods .......................................................................................17 2.2.1 Experimental animals..............................................................................17 2.2.2 Survival study .........................................................................................17 2.2.3 Establishment of acute colitis .................................................................17 2.2.4 Histologic analysis ..................................................................................18 2.2.5 Protein extraction and Western blotting analysis ....................................18 2.2.6 Protein co-immunoprecipitation .............................................................19 2.2.7 Colon tissue culture and enzyme-linked immunosorbent assay .............20 2.2.8 Cell culture .............................................................................................20 2.2.9 Adiponectin recombinant protein treatment ...........................................21 2.2.10 RNA extraction, cDNA synthesis and reverse transcription-quantitative polymerase chain reaction (qPCR) .........................................................21 2.2.11 Immunohistochemistry quantification ....................................................22 2.2.12 Statistical analysis ...................................................................................22 2.3 Results ................................................................................................................23 2.3.1 The expression of adiponectin and adiponectin receptor 1 ....................23 2.3.2 DSS-induced colitis ................................................................................23 2.3.3 Macrophage infiltration ..........................................................................24 2.3.4 IL-6 and TNF-α in mouse serum and colonic tissue culture medium ....24 2.3.5 Adiponectin in mouse serum ..................................................................25 2.3.6 The effect of adiponectin on the cyclooxygenase/prostaglandin E2 pathway ...................................................................................................25 2.3.7 Adiponectin enhanced the expression of IL-8 ........................................26 2.3.8 The effect of adiponectin on pro-inflammatory cytokines .....................26 2.3.9 Adiponectin receptor 1 enhanced the expression of neutrophil chemokines, cox2 and elastase in mice colon tissue ..............................26 2.4 Discussion ...........................................................................................................28 2.5 Conclusions ........................................................................................................32 References ......................................................................................................................51 Appendix Docosahexaenoic acid suppresses pro-inflammatory macrophages and promotes anti-inflammatory/ regulatory macrophage polarization through regulation of cytokines .........................................................................................................................69 A.1 Abstract ....................................................................................................................69 A.2 Introduction ..............................................................................................................70 A.3 Materials and Methods .............................................................................................72 A.3.1 Cell culture ....................................................................................................72 A.3.2 DHA treatment and macrophage differentiation ...........................................72 A.3.3 RNA extraction and reverse transcription-quantitative polymerase chain reaction (qRT-PCR) ......................................................................................73 A.3.4 Experimental Animals and DHA administration ..........................................73 A.3.5 Flow cytometry .............................................................................................74 A.3.6 Enzyme-linked immunosorbent assay (ELISA) ...........................................75 A.3.7 Statistical analysis .........................................................................................75 A.4 Results ......................................................................................................................76 A.4.1 Pre-treatment with DHA reduced the expression of M1 markers in THP-1 cells ......................................................................................................................76 A.4.2 Pre-treatment with DHA increased the expression of M2 and Mreg markers in THP-cells ...............................................................................................................76 A.4.3 DHA decreased M1 and increased M2-like macrophages in mice .................77 A.4.4 DHA decreased M1-stimulating cytokines and increased M2/Mreg- stimulating cytokines in mice .........................................................................77 A.5 Discussion ................................................................................................................78 Appendix references .......................................................................................................89 List of Tables Table1-1 Dual roles of neutrophils ..................................................................................10 Table 2-1 Primer sets for quantitative real-time PCR .......................................................33 Table A1 Primers sets for quantitative real-time PCR ....................................................82 List of Figures Figure 1-1 Domains and structure of adiponectin ............................................................11 Figure 2-1 Sequence alignment of human, pig and mouse AdipoR1 ................................34 Figure 2-2. Mouse ADN recombinant protein induced the phosphorylation of AMPK in porcine adipocyte ........................................................................................................35 Figure 2-3 Mouse ADN bound to porcine AdipoR1 in pAdipoR1 mice ...........................36 Figure 2-4 Experimental design ......................................................................................37 Figure 2-5 The expression of adiponectin and adiponectin receptor 1 in wild type (WT) and porcine adiponectin receptor 1 transgenic mice (pAdipoR1) ................................38 Figure 2-6 The responses of wild type mice (WT) and porcine adiponectin receptor 1 transgenic mice (pAdipoR1) to DSS-induced colitis .................................................40 Figure 2-7 The expression of pro-inflammatory cytokines in serum and colon of wild type mice (WT) and porcine adiponectin receptor 1 transgenic mice (pAdipoR1) .................................................................................................................42 Figure 2-8 The expression of adiponectin in serum of wild type mice (WT) and porcine adiponectin receptor 1 transgenic mice (pAdipoR1) ......................................................44 Figure 2-9 The expression of inflammatory markers in a colon epithelial cell line (HT-29 cells) .......................................................................................................................45 Figure 2-10 The expression of inflammatory markers in macrophages .........................46 Figure 2-11 The expression of neutrophil chemokines in the colon of mice .................48 Figure 2-12 The expression of pro-inflammatory factors and neutrophils in the colon of mice ............................................................................................................................49 Figure 2-13 Proposed model of the ADN-AdipoR1 effect in colitis ..............................50 Figure A1 Pre-treatment with DHA reduced expression of M1 markers in THP-1 cells .............................................................................................................................83 Figure A2 Pre-treatment with DHA increased expression of M2 and Mreg markers in THP-1 cells lines ........................................................................................................84 Figure A3 Administration of DHA decreased the percentage of M1 and increased the percentage of M2-like cells in mice ...........................................................................86 Figure A4 Administration of DHA decreased M1 polarization stimulating cyto- kine secretion and increased M2 and Mreg polarization stimulating cytokine secretion in mouse plasma .............................................................................................................88 | |
| dc.language.iso | en | |
| dc.subject | 發炎性腸道疾病 | zh_TW |
| dc.subject | 脂聯素 | zh_TW |
| dc.subject | 脂聯素一型接受體 | zh_TW |
| dc.subject | 嗜中性球 | zh_TW |
| dc.subject | 介白素8 | zh_TW |
| dc.subject | 趨化因子 | zh_TW |
| dc.subject | adiponectin | en |
| dc.subject | inflammatory bowel disease | en |
| dc.subject | chemokine | en |
| dc.subject | IL-8 | en |
| dc.subject | neutrophil | en |
| dc.subject | adiponectin receptor 1 | en |
| dc.title | 激活脂聯素一型接受體惡化發炎性腸道疾病 | zh_TW |
| dc.title | Activation of adiponectin receptor 1 exacerbates inflammatory bowel disease | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 陳明汝(Ming-Ju Chen),陳洵一(Shuen-Ei Chen),陳彥伯(Yen-Po Chen),林原佑(Yuan-Yu Lin) | |
| dc.subject.keyword | 發炎性腸道疾病,脂聯素,脂聯素一型接受體,嗜中性球,介白素8,趨化因子, | zh_TW |
| dc.subject.keyword | inflammatory bowel disease,adiponectin,adiponectin receptor 1,neutrophil,IL-8,chemokine, | en |
| dc.relation.page | 93 | |
| dc.identifier.doi | 10.6342/NTU201900318 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-01-31 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 動物科學技術學研究所 | zh_TW |
| 顯示於系所單位： | 動物科學技術學系 | |
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