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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 許秉寧(Ping-Ning Hsu) | |
dc.contributor.author | Ying-Chao Hsueh | en |
dc.contributor.author | 薛穎超 | zh_TW |
dc.date.accessioned | 2021-06-16T17:20:05Z | - |
dc.date.available | 2017-09-18 | |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-17 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63823 | - |
dc.description.abstract | Chronic hepatitis B infection (HBV) is closely correlated to elevated risks of liver cirrhosis and hepatocellular carcinoma. However, the underlying mechanisms leading to viral persistency are not fully understood. Among the viral factors, HBV core protein has been identified being critical for HBV persistence. On the other hand, type I interferons and TNF-α are host factors required for HBV clearance. Hence, we hypothesize that the HBV mutants might evade essential innate immune responses which lead to its persistence in human host. Using reporter assay in the hydrodynamic injection mouse model, we found that WT HBV could induce higher IFN-β promoter activity than persistent HBc mutants. The Kupffer cells also expressed more pro-inflammatory cytokine genes in response to WT HBV. As the HBV mutants harboring structural changes in the HBV core region might lead to variable outcomes of innate immune response, we then characterized the stimulatory effect of recombinant HBc in vitro with macrophage and dendritic cell line. HBc could stimulate DC to secrete TNF-α through a calcium-dependent and Syk-dependent manner in which the HBc capsid structure was also required. Furthermore, the role of Kupffer cells in viral clearance was assayed by clodronate-liposome treatment to deplete Kupffer cells in mice treated with HBV hydrodynamic injection; however, HBV was still cleared in the absence of Kupffer cells. Our study indicated that HBc had a stimulatory effect on antigen-presenting cells which leaded to the induction of innate immunity. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T17:20:05Z (GMT). No. of bitstreams: 1 ntu-101-R98449014-1.pdf: 1829912 bytes, checksum: 3399e5bf9cc9600d0a1eac26a00d6357 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 誌謝 i
Abstract ii 中文摘要 iii List of Figures vi Chapter 1 Introduction 1 1.1 background 1 1.1.1 Innate immunity in HBV 1 1.1.2 Role of HBV core protein 2 1.1.3 Tolerogenic liver environment 3 1.1.4 Innate immune responses of Kupffer cells and other antigen presenting cells against HBV 4 1.2 Rationale 6 1.3 Specific aims 7 Chapter 2 Material and methods 8 2.1 Materials 8 2.1.1 Antibodies 8 2.1.2 Reagents 9 2.1.3 Medium and Buffers 10 2.2 Methods 11 Chapter 3 Results 18 3.1 HBV DNA induces IFN-β promoter activation 18 3.2 HBV DNA up-regulates interferon-stimulated genes (ISGs) expression 19 3.3 Kupffer cells up-regulate pro-inflammatory cytokine mRNA expression in response to HBV 19 3.4 Recombinant HBc protein stimulates dendritic cells to secrete TNF-α in vitro 20 3.5 The HBc capsid structure is required for stimulating dendritic cells 22 3.6 Recombinant HBc protein induces IL-6 mRNA expression in macrophages 22 3.7 The HBV persistent rate did not change significantly in Kupffer cells-depleted BALB/c mice by clodronate-liposome treatment 23 Chapter 4 Discussion 25 4.1 WT HBV induces type I interferon response 25 4.2 The role of Kupffer cells in HBV viral clearance 26 4.3 HBc capsid activates dendritic cells to secrete TNF-α in vitro 31 Chapter 5 Conclusions and working hypothesis 38 5.1 Conclusions 38 5.2 Working hypothesis 39 Figures 40 Reference 53 | |
dc.language.iso | en | |
dc.title | 在小鼠動物模式中探討B型肝炎病毒核心蛋白所引發的先天性免疫反應 | zh_TW |
dc.title | Induction of innate immunity by HBV core protein in mouse animal model | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳培哲(Pei-Jer Chen),謝世良(Shie-Liang Hsieh),陳俊任(Chun-Jen Chen),朱清良(Ching-Liang Chu) | |
dc.subject.keyword | B型肝炎病毒,核心蛋白,先天性免疫,腫瘤壞死因子-α,脾臟酪胺酸激酶,庫氏細胞, | zh_TW |
dc.subject.keyword | hepatitis B virus,HBc,innate immunity,TNF-α,Syk,Kupffer cell, | en |
dc.relation.page | 63 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-17 | |
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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