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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐立中(Li-Chung Hsu) | |
| dc.contributor.author | Yun-Yun Young | en |
| dc.contributor.author | 楊昀芸 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:48:07Z | - |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-03 | |
| dc.identifier.citation | Akira, S., and Takeda, K. (2004). Toll-like receptor signalling. Nature reviews Immunology 4, 499-511.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19189 | - |
| dc.description.abstract | Upon pathogen infection, inflammatory cytokines are induced to mount an inflammatory response to defend against pathogens. However, while impaired innate immunity renders the host more vulnerable to pathogenic infection, exceed and prolonged inflammation can cause many diseases. Thereby, anti-inflammatory cytokines, such as IL-10, are expressed at later stage of inflammation to counteract the effects of pro-inflammatory cytokines. To reach a disease-free state, the balance between inflammatory and anti-inflammatory responses must be spatially and temporally controlled. Previously our lab identified Zcchc6 (TUT7), a terminal uridylyltransferase, which was upregulated in murine macrophages upon Lipopolysaccharides (LPS) stimulation. Deprivation of Zcchc6 in macrophages resulted in downregulations of pro-inflammatory cytokines such as IL-6, IL12b and IFNβ, and an upregulation of anti-inflammatory cytokine IL-10. In the study we focus on how Zcchc6 regulates IL-10 expression upon LPS challenge. We found that Zcchc6 does not modulate IL-10 mRNA stability. Rather, Zcchc6 regulates IL-10 transcription. In addition, we demonstrated that STAT1, which is also induced by LPS, binds to the IL-10 promoter upon TLR4 engagement. STAT1 mRNA stability is increased in Zcchc6-deficient macrophages. Our results strongly suggest that Zcchc6 modulates STAT1 mRNA stability, which leads to regulation of IL-10 transcription in response to LPS. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:48:07Z (GMT). No. of bitstreams: 1 ntu-105-R03441015-1.pdf: 2617903 bytes, checksum: d9a8a2cb9ce5f10eab2a89d677df065a (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
Acknowledgement ii 摘要 iii Abstract iv Contents v Introduction 1 Toll-like receptor 4 (TLR4) and signaling 3 Zinc-finger containing proteins and their regulatory roles in TLR4-triggered immune responses 5 Zinc finger CCHC domain containing 6 (Zcchc6)/Terminal uridylyltransferase 7 (TUT7) 7 The function of Zcchc6 in TLR4-driven immune response 9 Specific aim 11 Materials and Methods 12 Reagents 12 Plasmids 12 Mice 13 Cell culture and transfection 13 Bone Marrow Derived Macrophages (BMDMs) preparation 14 shRNA-mediated gene silencing and lentiviral infection 15 Immunoblotting 16 Cytosolic and nuclear fractionation 17 Enzyme-Linked ImmunoSorbent Assay (ELISA) 17 Total RNA extraction and reverse transcription quantitative PCR (RT-QPCR) 18 mRNA stability assay 20 RNA immunoprecipitation 20 Chromatin immunoprecipitation 21 Electrophoretic mobility shift assay (EMSA) 23 Statistical analysis 24 Results 25 Zcchc6 is induced upon TLR4 activation and is involved in regulation of TLR4-driven cytokine productions 25 STAT1 is involved in Zcchc6-mediated IL-10 expression upon LPS stimulation 26 STAT1 is a novel transcription factor involved in IL-10 transcription in response to LPS 27 Zcchc6 regulates STAT1 mRNA stability 29 Zcchc6 plays dual regulatory roles in the induction of IL-10 expression in response to LPS 30 Dis3l2, an exonucleus, upregulates STAT1 mRNA but downregulates IL-10 mRNA upon LPS stimulation 31 Zcchc11 and Zcchc6 differentially regulates inflammatory cytokines upon LPS stimulation 32 Discussion 35 Figure 1. 41 Figure 2. 43 Figure 3. 44 Figure 4. 47 Figure 5. 48 Figure 6. 49 Figure 7. 51 Figure 8. 52 Figure 9. 53 Figure 10. 54 Figure 11. 55 Figure 12. 57 Figure 13. 58 Figure 14. 59 Figure 15. 61 Supplementary Figure 1. 62 Supplementary Figure 2. 64 Reference 65 | |
| dc.language.iso | en | |
| dc.title | 一個終端尿苷醯轉移酶調控TLR4誘導Interleukin-10的機轉 | zh_TW |
| dc.title | The Mechanism of a Terminal Uridyly Transferase in the regulation of TLR4-triggered Interleukin-10 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 譚婉玉(Woan-Yuh Tarn),詹世鵬(Shih-Peng Chan),蔡欣佑(Hsin-Yue Tsai) | |
| dc.subject.keyword | 發炎反應,第四型類鐸受體,終端尿?醯轉移?,介白素-10, | zh_TW |
| dc.subject.keyword | Inflammation,TLR4,Terminal Uridylytransferase,Interleukin-10, | en |
| dc.relation.page | 72 | |
| dc.identifier.doi | 10.6342/NTU201601806 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2016-08-03 | |
| 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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