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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐立中(Li-Chung Hsu) | |
| dc.contributor.author | Tzu-Ting Tseng | en |
| dc.contributor.author | 曾慈婷 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:12:10Z | - |
| dc.date.available | 2013-03-12 | |
| dc.date.copyright | 2010-03-12 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-01-26 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45280 | - |
| dc.description.abstract | 先天性免疫(innate immunity)主要是由具有吞噬能力的細胞如macrophage和dendritic cell所執行。有別於後天性免疫系統(adaptive immunity)所使用的經過體染色體重組之receptor，這些細胞利用特殊的PRR (pattern-recognition receptor)來偵測病原的存在。PRR為germ line-encoded並且辨認的是病原體尋常且共通的成分PAMPs (pathogen-associated molecular patterns)，如LPS (lipopolysaccharide，革蘭氏陰性菌的細胞壁成分)、核酸等。偵測到病原體可引發細胞內訊息傳遞，促進細胞激素的釋放並且啟動發炎反應。發炎反應有助於病原體的清除，不過，過度的發炎反應卻是引發疾病的重要因素，諸如癌症、動脈硬化、第二型糖尿病、敗血症和自體免疫疾病皆與慢性或失控的發炎有關。研究顯示，除了病原體之外，內部組織的損傷也可以是引發先天性免疫和發炎反應的因子(DAMPs, danger-associated molecular patterns)。
TLR (Toll-like receptor)家族屬於PRR之一員，在哺乳動物中已發現13個TLR，且對其受質、下游訊息傳遞都已累積相當多的研究。其中，TLR4主要偵測LPS，並透過TRIF和MyD88兩個主要的adaptor protein來進行訊息傳遞。過去研究已知TLR4透過TRIF和下游之TRAF3、TBK1來磷酸化IRF3，進而促進干擾素IFNβ的產生。另外亦有較新的研究發現，剔除Pkr基因之細胞在受到LPS刺激之後無法正常引發IFNβ之反應，顯示PKR參與在此訊息傳遞當中，但是並不清楚其細節。因此，本篇研究旨在闡明PKR參與在TLR4下游、促進IFNβ產生的機制。我們發現TBK1會調控PKR的活性，並且PKR的活性亦對TBK1有正向影響。除此之外，PKR尚扮演著另一重要角色，橋接TBK1到TRAF3、TRIF的signaling complex。這些發現讓我們對於TLR4的訊息傳遞有了更詳細的了解，也對於治療發炎、感染等造成之疾病有莫大助益。 | zh_TW |
| dc.description.abstract | Innate immunity is of great importance not only in host defense against infections, but also has been implicated in development and tissue homeostasis. Immune cells, such as macrophages, use pattern-recognition receptors (PRR) to sense microbes and dying cells and initiate inflammatory response that helps to fight the pathogen and assist tissue repair. However, the inflammation process must be finely tuned or it may turn out to be pathogenic. Among several classes of PRR, the mammalian TLR (Toll-like receptor) family comprises 13 membrane receptors which are able to recognize a range of conserved microbial motifs termed PAMPs (pathogen-associated molecular patterns) or endogenous DAMPs (danger-associated molecular patterns) released by stressed or damaged tissues and activate immune response.
PKR (dsRNA-dependent protein kinase) has been shown to be involved in IFNβ production and apoptosis in LPS-induced macrophages previously [1]. In this study we further characterize the functional role of PKR in the TLR4 signaling pathway. We found that TBK1 regulates PKR activation, which in turn enhances TBK1 kinase activity. We also demonstrated that PKR is required for maintaining the integrity of TRIF-TRAF3-TBK1 complex. Our findings further delineate the TLR4-TRIF signaling pathway after LPS stimulation, and could shed some light in advanced understanding of certain inflammatory and infectious diseases and development of therapies. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:12:10Z (GMT). No. of bitstreams: 1 ntu-99-R96448009-1.pdf: 1550691 bytes, checksum: 526f603445af1a531099b81250dd9494 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 致謝 i
摘要 ii Abstract iv Contents v Introduction 1 Results 11 Discussion 17 Materials and Methods 22 References 29 Figures 33 | |
| dc.language.iso | en | |
| dc.title | PKR在TLR4訊息傳遞中扮演之角色 | zh_TW |
| dc.title | Characterization of PKR function in TLR4 signaling | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林琬琬(Wan-Wan Lin),陳俊任(Chun-Jen Chen) | |
| dc.subject.keyword | 發炎反應,TLR4,PKR,TBK1, | zh_TW |
| dc.subject.keyword | inflammation,TLR4,PKR,TBK1, | en |
| dc.relation.page | 41 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-01-26 | |
| 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 | |
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