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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 莊立民(Lee-Ming Chuang) | |
dc.contributor.author | Kuan-Hsun Chen | en |
dc.contributor.author | 陳冠勳 | zh_TW |
dc.date.accessioned | 2021-06-15T00:33:24Z | - |
dc.date.available | 2011-02-10 | |
dc.date.copyright | 2009-02-10 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-01-12 | |
dc.identifier.citation | 1. Economic costs of diabetes in the U.S. In 2007. Diabetes Care, 2008. 31(3): p. 596-615.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/41828 | - |
dc.description.abstract | 第2型糖尿病現今已成為威脅全人類健康的一種疾病,目前第2型糖尿病已被廣泛的認為與肥胖所導致的輕微慢性發炎有關,此種發炎的特徵在於脂肪組織中出現大量巨噬細胞及其所分泌的炎症性細胞激素。介白素10是一種多功能性的細胞激素,可借由抑制炎症性的細胞激素來調控免疫及發炎反應,在脂肪組織中的巨噬細胞所釋放的介白素10可結抗發炎反應,並且保護脂肪細胞免於傷害。在本篇研究中,藉由PMA所誘導分化的人類巨噬細胞,吾人發現15-keto-PGE2 可誘使抗發炎的介白素10之生成,但不會誘使發炎反應的細胞激素生成。而15-keto-PGE2主要是藉由PI3K/AKT/GSK-3β的訊息傳遞途徑來誘使介白素10之生成。15-keto-PGE2 可藉由增強轉錄因子CREB及Sp1對於介白素10 promoter的結合能力來調控介白素10,除此之外,15-keto-PGE2 也經由過氧化氫受體γ之途徑來調控介白素10。綜合以上,這些結果開拓了15-keto-PGE2於調控抗發炎上之重要角色,以及增強了前列腺素代謝反應在免疫反應調控上之重要性。 | zh_TW |
dc.description.abstract | Type 2 diabetes (T2D) mellitus is currently one of the main health treats for humans. It is now broadly accepted that low-grade chronic inflammation associated with obesity leads to the onset of type 2 diabetes. Obesity-associated inflammation is characterized by an increased abundance of macrophages in adipose tissue along with the production of inflammatory cytokines. Interleuikin-10 (IL-10) is a pleiotropic cytokine that mediate immune and inflammatory responses by inhibiting the synthesis of pro-inflammatory cytokines. IL-10 secreted from macrophages in adipose tissue may counteract the inflammatory effects and protect adipose tissue from injuring. In this study, by using PMA-differentiated THP-1 macrophages, we demonstrated that 15-keto-PGE2 could induce the anti-inflammatory cytokine IL-10 production, but not the pro-inflammatory cytokines (TNF-α, IL-6 and IL-12). The capacity of 15-keto-PGE2 to elevate IL-10 expression level was mediated through PI3K/AKT/GSK-3β signaling pathway. 15-keto-PGE regulated IL-10 promoter activation by increasing the binding activities of transcription factors, CREB and Sp1. Furthermore, 15-keto-PGE2 also induced IL-10 production through partial PPARγ-dependent pathway. Taken together, these findings explore the crucial role of 15-keto-PGE2 in anti-inflammatory effect and enforce the importance of PGE2 catabolism in the immune response. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T00:33:24Z (GMT). No. of bitstreams: 1 ntu-98-R95448011-1.pdf: 1100319 bytes, checksum: d9e47f6989a342e2802b43423b13a00e (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 謝誌 I
中文摘要 II Abstract III Table of contents IV Introduction 1 I. Obesity, insulin resistance and Type 2 Diabetes 2 II. Inflammation – linked obesity to Type 2 Diabetes 3 The main origin of the systemic inflammatory response is located in adipose tissue 3 The infiltration of macrophage causes local inflammation in adipose tissue 5 III. Peroxisome proliferator-activated receptors (PPARs) 8 Macrophage PPARγ is a crucial regulator of inflammation and insulin resistance 9 IV. Anti-inflammatory cytokine - Interleukin-10 (IL-10) 11 V. Prostaglandins (PGs) 12 Prostaglandin E2 and its metabolites 13 Materials and methods 15 Reagents 15 Cell culture 15 Prepare whole cell extraction 15 Western blot analysis 16 RNA isolation and Real-Time PCR 17 Enzyme-Linked Immunosorbent Assay (ELISA) 18 Chromatin Immunoprecipitation (ChIP) Assay 18 Statistical Analysis 19 Results 20 PMA induced differentiation of human THP-1 cells 20 15-keto-PGE2 induced the anti-inflammatory cytokine IL-10 mRNA and protein levels in human THP-1 derived macrophages 20 Differential effects of 15-keto-PGE2 and other PPARγ agonists on IL-10 production in human THP-1 cells 21 15-keto-PGE2 stimulated IL-10 expression through PPARγ-dependent pathway 22 The effect of 15-keto-PGE2 on IL-10 production was mediated by PI3K/AKT pathway 22 Role of MAPK family in the 15-keto-PGE2 activated IL-10 production 23 Transcription factors binding to the IL-10 promoter in situ 24 Conclusion and Discussion 26 PPARγ ligands in immune regulation 26 Prostaglandin and its receptor on the cytokine regulation 28 Transcriptional control of IL-10 production 28 Our findings in drug discovery for the Type 2 diabetes mellitus therapy 30 Figures and Tables 31 FIG. 1 Characterization of human THP-1 derived macrophages. 31 FIG. 2 15-keto-PGE2 up-regulates the anti-inflammatory cytokine IL-10, but not pro-inflammatory cytokines in human THP-1 cells. 32 FIG. 3 15-keto-PGE2 induces IL-10 mRNA and protein expression in a dose- and time-dependent manner in human THP-1 derived macrophages. 33 FIG. 4 Effects of different PPARγ agonists on the IL-10 production by THP-1 cells. 34 FIG. 5 Effect of 15-keto-PGE2 on IL-10 production is mediated through PPARγ-dependent pathway. 35 FIG. 6 Effect of 15-keto-PGE2 on IL-10 production is mediated through PI3K/AKT but not PKA signaling pathway. 37 FIG. 7 Role of MAPK family in the 15-keto-PGE2 activated IL-10 production 39 FIG. 8 Activation of CREB and Sp1 binding at the IL-10 promoter by 15-keto-PGE2 in THP-1 derived macrophages. 41 FIG. 9 Proposed model for regulation of IL-10 production by 15-keto-PGE2 42 Supplemental Data 43 Figure S1. Effects of different PPARγ agonists in various dose on the IL-10 production by THP-1 derived macrophages. 43 Figure S2. The expression of PTGR-2 during THP-1 derived macrophage differentiation. 44 Table 1. Nucleotide sequence of the promoter region of hIL-10 gene 45 References 46 | |
dc.language.iso | en | |
dc.title | 探討15-keto-PGE2於人類巨噬細胞中對介白素10的影響 | zh_TW |
dc.title | The effects of 15-keto-PGE2 on IL-10 production in human macrophages | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林琬琬,余家利 | |
dc.subject.keyword | 第2型糖尿病,介白素10,15-keto-PGE2,巨噬細胞,過氧化氫受體γ, | zh_TW |
dc.subject.keyword | 15-keto-PGE2,Interleukin-10,PPARγ,THP-1 cell,macrophage, | en |
dc.relation.page | 58 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-01-13 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
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ntu-98-1.pdf 目前未授權公開取用 | 1.07 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。