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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 莊曜宇 | |
dc.contributor.author | Shang-Duen Wu | en |
dc.contributor.author | 吳尚暾 | zh_TW |
dc.date.accessioned | 2021-06-13T00:25:53Z | - |
dc.date.available | 2016-08-22 | |
dc.date.copyright | 2011-08-22 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-21 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28851 | - |
dc.description.abstract | 巨噬細胞能夠辨識並且消滅外來的病原體,因此在免疫系統中扮演一個非常重要的角色。巨噬細胞表面上的TLRs在與病原體物質結合之後能透過細胞內的調 控子來啟動訊息傳遞。TLR4是最主要能對脂多醣產生反應的受器,並且能藉此誘發下游的調控因子在最終活化IKK和一些MAPKs像是ERK、JNK、p38。在之前 的研究已經顯示,巨噬細胞中有一些經由脂多醣所誘發表現的基因除了NFκB之外,還需要另一個受p38影響的轉錄因子的調控。因此,本篇論文的主題是要找 出這些同時受到 NFκB 和 p38 調控的基因及其轉錄因子。
本篇研究顯示,由正常的、剔除Ikkβ基因的、利用SB202190抑制p38的三種老鼠BMDMs細胞所進行的微陣列晶片數據分析中,我們挑選出55個候選基因。其中16個和免疫細胞移動功能相關的基因之啟動子被用來進行轉錄因子結合位的預測。由預測結果顯示,在Tnfaip3和Zc3h12a這兩個基因的啟動子中預測到了NF-κB p65與C/EBPβ結合位的存在。藉由進行染色體免疫沈澱實驗,我們能夠驗證在老鼠 RAW264.7巨噬細胞中p65與C/EBPβ在這些結合位的結合活性。實驗結果顯示,p65和C/EBPβ在脂多醣刺激的四個小時後能在Tnfaip3的啟動子上觀察到最大量的結合。然而,這個結合現象卻在利用SB202190抑制p38之後受到抑制。 由此得知,C/EBPβ可能是一個受p38影響且會與NF-κB共同進行Tnfaip3轉錄調控的轉錄因子。 | zh_TW |
dc.description.abstract | Macrophages play a pivotal role in immune system through recognition and elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages interact with microbial substances and initiate signal transduction through intracellular adapters. TLR4, which is important for response to lipopolysaccharide (LPS), triggers downstream signaling mediators and eventually activates IκB kinase (IKK) and mitogen-activated protein kinases (MAPKs) such as ERKs, JNKs, and p38 MAPKs. Previous reports reveal that, in addition to NF-κB, the induction of some LPS-inducible genes in macrophages requires a second transcription factor whose activity depends on p38. Therefore, the specific aim of this thesis was to identify genes both regulated by NF-κB and p38 pathway, and their transcription factors that interact with NF-κB.
This study showed that 55 candidate genes were identified by microarray analysis using mouse bone marrow derived macrophages (BMDMs) of wild-type, IkkβΔ, and p38-inhibited by SB202190. Among these, promoters of 16 genes involved in immune cell movement were applied for transcription factor binding site prediction. As a result, NF-κB p65 and C/EBPβ binding sites were predicted in the promoters of Tnfaip3 and Zc3h12a. Chromatin immunoprecipitation (ChIP) assay was performed to validate the binding activity of p65 and C/EBPβ on predicted binding sites in mouse macrophages RAW264.7 cells. ChIP assays showed abundant bindings of p65 and C/EBPβ on Tnfaip3 promoter at 4 hours after LPS treatment. However, the binding activities of p65 and C/EBPβ were suppressed in the presence of SB202190, suggesting that C/EBPβ may be the p38-dependent synergistic transcription factor interacting with NF-κB for the regulation of Tnfaip3 expression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T00:25:53Z (GMT). No. of bitstreams: 1 ntu-100-R98945037-1.pdf: 9347575 bytes, checksum: 0fe58cb7964265aabdfd69d7f51441e0 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 中文摘要.....i
Abstract.....ii CONTENTS.....iv FIGURE CONTENTS.....v TABLE CONTENTS.....vi Chapter 1 Introduction.....1 1.1 Macrophages and TLR Signaling in Immune System .....1 1.2 Regulation of NF-κB in immune system.....2 1.3 Signaling of the p38 MAPK Pathway.....3 1.4 The Regulation Role of Tnfaip3 (A20) in Inflammatory Response.....4 1.5 Immune Response Controlled by Zc3h12a.....5 1.6 Motivation and Specific Aims.....6 Chapter 2 Materials and Methods.....7 2.1 Macrophage Preparation.....7 2.2 Microarray Experiments.....8 2.3 Microarray Data Analysis.....9 2.4 RNA Extraction and Quantitative Real-time RT-PCR.....10 2.5 Transcription Factor Binding Site (TFBS) Prediction.....11 2.6 Chromatin Immunoprecipitation (ChIP) Assay.....12 Chapter 3 Results.....14 3.1 Microarray Experiment.....14 3.2 Microarray Analysis.....17 3.3 Microarray Analysis: Identification of p38-Dependent NF-κB Target Genes in Activated Macrophages.....19 3.4 Microarray Analysis: Functional Analysis of 55 Genes Regulated Both by NF-κB and p38 pathway.....24 3.5 NFκB and p38-regulated Transcription Factor Binding Site Prediction.....26 3.6 LPS Induced the Recruitments of p65 and C/EBPβ to the Predicted Binding Sites Within Tnfaip3 Promoter.....30 Chapter 4 Discussion .....34 4.1 Preparation and Differentiation of BMDMs.....34 4.2 IkkβΔ and p38-inhibition BMDMs.....34 4.3 55 LPS-inducible Genes as Candidates of p38-depentdent NF-κB Target Genes in Macrophages.....36 4.4 Expression of Tnfaip3 Regulated by C/EBPβ and NF-κB.....38 4.5 Future Work.....39 References.....41 | |
dc.language.iso | en | |
dc.title | 於活化之巨噬細胞中鑑定共同受NF-κB及p38訊息傳遞調控的轉錄因子 | zh_TW |
dc.title | Identification of Synergistic Transcription Factors that Respond to NF-κB and p38 Signaling Pathway in Activated Macrophages | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 賴亮全 | |
dc.contributor.oralexamcommittee | 蔡孟勳,徐立中 | |
dc.subject.keyword | NF-κB,p38,巨噬細胞,脂多醣,染色體免疫沈澱,C/EBPβ,Tnfaip3, | zh_TW |
dc.subject.keyword | NF-κB,p38,macrophages,LPS,Chromatin immunoprecipitation,C/EBPβ,Tnfaip3, | en |
dc.relation.page | 50 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2011-08-21 | |
dc.contributor.author-college | 電機資訊學院 | zh_TW |
dc.contributor.author-dept | 生醫電子與資訊學研究所 | zh_TW |
顯示於系所單位: | 生醫電子與資訊學研究所 |
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