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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 | Hung-An Ting | en |
dc.contributor.author | 丁竑安 | zh_TW |
dc.date.accessioned | 2021-06-08T05:10:08Z | - |
dc.date.copyright | 2011-10-05 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-07-18 | |
dc.identifier.citation | REFERENCE
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23789 | - |
dc.description.abstract | PSTPIP2是一個37kD的蛋白質,屬於Pombe cdc 15 homology family,這個家族的蛋白質主要的功能是扮演細胞膜和細胞骨架之間的coordinator的角色。之前已經有文獻報導,在ENU老鼠突變模式中,PSTPIP2的點突變所造成的兩種錯義突變—I282N和L98P的老鼠,在骨頭和皮膚會有自體發炎的症狀,而且突變對老鼠巨噬細胞的增殖能力和脂多醣引起的細胞激素分泌有影響。但是對於PSTPIP2是否會直接影響在巨噬細胞脂多醣引起的發炎反應和產生發炎所需的訊息傳導路徑,仍然不清楚。我們利用RAW264.7這個細胞株作為研究材料,看在用siRNA降低PSTPIP2的表現時,脂多醣所引發的發炎反應是否有影響。我們發現脂多醣所引起的腫瘤壞死因子α,介白素第六因子和inducible Nitric Oxide Synthase分泌量減少了,而介白素第十因子分泌量有些微上升。我們進一步去看訊息傳導。在脂多醣所引起的發炎反應中,先看對於發炎細胞激素產生很重要的NF-κB和MAPK訊息傳遞路徑,發現IKK, IκB的磷酸化和NF-κB入核的情況並沒有明顯的差異,p38, JNK, ERK的磷酸化也沒有減少。由於之前的文獻指出,PSTPIP2 和PI[4,5]P2有很高的親合力,所以猜測PSTPIP2是否會影響PI3K-Akt 訊息傳遞路徑。發現siRNA降低PSTPIP2的表現時,Akt和GSK3β磷酸化增加了。另外因為脂多醣所引起的腫瘤壞死因子α在2小時沒有因為抑制PSTPIP2表現而減少,這樣的情況在IFN regulator看到類似的結果,所以我們也猜測PSTPIP2可以調控TRIF訊息傳遞路徑。脂多醣所引起的TRIF訊息傳遞路徑可以活化IRF3,我們發現在siRNA降低Pspip2的表現時,脂多醣所引起的干擾素β產生和IRF3磷酸化、雙體化會被抑致,但是聚肌苷酸聚胞苷酸所引起的IRF3磷酸化和雙體化卻不會被抑致。從以上的初步實驗結果我們發現,PSTPIP2可以調控TLR4而非TLR3訊息傳遞路徑其下游的IRF3活化和干擾素β產生,也影響腫瘤壞死因子α,介白素第六因子,inducible Nitric Oxide Synthase 和PI3K-Akt 訊息傳遞路徑。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-08T05:10:08Z (GMT). No. of bitstreams: 1 ntu-100-R98449001-1.pdf: 4772588 bytes, checksum: f2e8d4dadabeb460bae68c755842b2f7 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 iii ABSTRACT iiii CONTENTS iv ChapterⅠ Introduction 1 1.1 Background 2 1.1.1 Proline, Serine, Threonine Phosphatase Interacting Protein 2(PSTPIP2) 2 1.1.2 Mutation of Pstpip and Autoinflammatory Diseases. 4 1.1.3 Toll-like Receptor 4 and Inflammation. 6 1.1.4 PI3K-Akt Axis in Regulating LPS-induced inflammatory responses and signaling pathways. 10 1.2 Motivations and Aims of this study 11 ChapterⅡ Materials and Methods 13 2.1 Materials 14 2.1.1 Antibodies 14 2.1.2 Chemicals and Reagents 15 2.1.3 Medium and Buffer 17 2.1.4 General Materials 18 2.2 Methods 19 2.2.1 Cell Culture 19 2.2.2 RNA-mediated Interference 19 2.2.3 Site-directed Mutagenesis 19 2.2.4 Vector Transfection 20 2.2.5 Cell Lysate Preparation 21 2.2.6 Immunoblot Analysis 21 2.2.7 Enzyme-linked Immunosorbent Assay (ELISA) 22 2.2.8 Quantitative Real-time Polymerase Chain Reaction 22 2.2.9 Electrophoretic Mobility Shift Assay (EMSA) 24 2.2.10 IRF3-dimerization Assay 25 2.2.11 Statistical Analysis 25 ChapterⅢ Results 26 3.1 PSTPIP2 positively regulates TLR2,3,4 ligand-induced TNF-α, TLR4 ligand-induced IL-6 production and negatively regulates LPS-induced IL-10 production 27 3.2 LPS-induced iNOS, but not COX-2, is positively regulated by PSTPIP2 28 3.3 PSTPIP2 has different roles in a dose-dependent manner to modulate LPS-induced NF-kB translocation and IkB phosphorylation 29 3.4 PSTPIP2 do not regulate LPS-induced P38, JNK, ERK phosphorylation 31 3.5 LPS-induced Akt and GSK3β phosphorylation are increased in Pstpip2-knockdown RAW264.7 31 3.6 PSTPIP2 modulates LPS-induced IRF3 phosphorylation, dimerization and IFNβ production 32 3.7 LPS-induced STAT1 phosphorylation has no conspicuous differences in Pstpip2-knockdown RAW264.7 33 Chapter Ⅳ Discussions 35 4.1 PSTPIP2 36 4.1.1 PSTPIP2 and PTP-PEST/ PTP-HSCF 36 4.1.2 The different role of PSTPIP2 in ENU mouse model and RAW264.7 in LPS-induced TNF-α and IL-6 production 37 4.2 Effect of PSTPIP2 on NF-κB and IRF3 39 4.2.1 Modifications of LPS-induced NF-κB activity 39 4.2.2 TLR3- and TLR4-triggered IRF3 activation 40 4.3 Akt-GSK3β axis in regulating NF-κB, IRF3, and cytokine production 44 4.4 Conclusions and Working Hypothesis 46 REFERENCE 47 FIGURES 57 | |
dc.language.iso | en | |
dc.title | PSTPIP2調控脂多醣在鼠巨噬細胞所引起的發炎反應 | zh_TW |
dc.title | PSTPIP2 Modulates Lipopolysaccharide-induced Inflammatory Responses in Murine Macrophage | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林琬琬(Wan-Wan Lin),陳俊任(Chun-Jen Chen) | |
dc.subject.keyword | 脂多醣,發炎,訊息傳導, | zh_TW |
dc.subject.keyword | lipopolysaccharide,inflammation,signaling transduction,toll-like receptor 4,tlr4, | en |
dc.relation.page | 72 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-07-18 | |
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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