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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 朱清良(Ching-Liang Chu) | |
| dc.contributor.author | Jenn-Yeu Shin | en |
| dc.contributor.author | 忻振宇 | zh_TW |
| dc.date.accessioned | 2021-07-10T21:42:53Z | - |
| dc.date.available | 2021-07-10T21:42:53Z | - |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-07-29 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76998 | - |
| dc.description.abstract | 主要分布在粒線體基質的Lon蛋白酶扮演相當多角色，最主要的功能是分解粒線體中受損的蛋白。大多數關於Lon的研究顯示，過度表達Lon蛋白酶可以促使癌細胞增生、減緩細胞凋亡，甚至促使轉移的發生。然而，尚未有研究關注Lon如何調節免疫細胞。李岳倫老師團隊的初步數據顯示，具有抗發炎特性的M2a和M2c這兩類巨噬細胞中，Lon蛋白酶表現上升。根據此現象，我們認為Lon蛋白酶在調節型樹突細胞中，也會被誘導而表達。首先，我們透過篩選找出潛在的刺激物能夠同時培養出調節型樹突細胞，也能高度誘導Lon蛋白酶表現。其中，我們觀察到藥物地塞米松能達到上述的效果。接著，我們調整培養條件去確認骨髓衍生樹突細胞中，地塞米松能誘導Lon蛋白酶表現上升。我們列出了潛在的候選基因，來解答地塞米松和Lon蛋白酶之間的訊息路徑，發現GILZ和STAT3有參與其中。最後，我們使用粒線體電子傳遞鏈的抑制劑，發現抑制氧化磷酸化會降低抗發炎的指標。我們推測，經由地塞米松誘導的Lon蛋白酶促使樹突細胞改變代謝路徑，造成電子傳遞鏈中的氧化酶表現上升，而旺盛的氧化磷酸化則再影響了調節型的表現型和功能。 | zh_TW |
| dc.description.abstract | Lon protease, encoded by Lonp1 gene in nucleus, plays multiple roles in mitochondrial matrix. The main function of Lon protease is degradation of damaged proteins. The majority of Lon studies have demonstrated that overexpression of Lon protease promotes the proliferation, anti-apoptosis, and epithelial-mesenchymal transition (EMT) of cancer cells. However, the role of Lon in regulating immune cell has not been reported. Preliminary data from Dr. Lee group showed that Lonp1 expression was up-regulated in M2a and M2c macrophages, which possess anti-inflammatory phenotypes. Hence, we propose that Lon could also be induced in regulatory type of dendritic cells (regDCs). First of all, we managed to find the inducer for Lonp1 expression by screening different stimuli for regDC generation. Then, we observed that Lonp1 expression was highly induced in Dexamethasone (DEX)-treated bone marrow-derived dendritic cells (BMDCs). Next, we modified culturing protocol and confirmed the upregulation of Lon induced by DEX in BMDCs. In addition, we found that glucocorticoid-induced leucine zipper (GILZ) and signal transducer and activator of transcription 3 (STAT3) may take part in this signaling pathway. Last, we tried to study the role of Lon in the phenotype and function of DEX-induced regDCs. Inhibition of oxidative phosphorylation (OXPHOS) would affect M2/regDC-associated genes in DEX-induced regDCs, which suggests that metabolic pathway would affect regulatory phenotypes. We propose that the upregulation of Lon may promote OXPHOS through activation of different subunits of cytochrome c oxidase (COXs) and contribute to the regulatory phenotype. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:42:53Z (GMT). No. of bitstreams: 1 U0001-2807202014260500.pdf: 2673886 bytes, checksum: f3f372dceb74a9d76dcd1907e8e8fc00 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝 i 中文摘要 ii Abstract iii Content v Figures Content vi Tables content viii Chapter 1. Introduction 1 1.1 Lon protease 1 1.2 Dendritic cells and regulatory dendritic cells 2 1.3 Dexamethasone 4 1.4 M2/regDC-associated genes 5 1.5 Metabolic pathways in dendritic cells 6 Chapter 2. Rationale and specific aims 8 2.1 Rationale 8 2.2 Specific Aims 8 Chapter 3. Material and methods 9 3.1 Material 9 3.2 Methods 11 Chapter 4. Results 14 4.1 The inductions of Lonp1 expression in various treatments for regDC generation 14 4.2 DEX highly induced the expression of Lon 14 4.3 The mRNA expressions or protein expressions of various signaling molecules after dexamethasone treatment 16 4.4 The effects of various inhibitors on the Lonp1 expression in DEX-induced regDCs 18 4.5 Stat3 may participate in the up-regulation of Lonp1 by DEX treatment 19 4.6 Overexpression of Lon may reduce the LPS responses in DC2.4 cells 20 4.7 The level of ROS was not affected by DEX treatment 20 4.8 The expression of COX4-1 increased with the treatment of DEX. 20 4.9 Inhibition of OXPHOS would affect the expression of M2/regDC-associated genes 21 4.10 DEX also induced the expression of Lon in BMDCs from BALB/c mice 23 Chapter 5. Discussion 24 5.1 Highly-expressed M2 markers were observed in DEX-induced regDCs 24 5.2 The expression patterns of IL-10 and Lon are similar, suggesting the same signaling molecules may be involved. 24 5.3 Lon plays a key role in cancer cells under oxidative stress which is associated with the pro-inflammatory phenotype in dendritic cells. 25 5.4 Highly-expressed Lon may modulate the metabolic state through its diverse functions in DEX-induced regDCs 27 5.5 Over-expressing Lon in BMDCs can elucidate the role of Lon in regDCs 28 Chapter 6. Figures Tables 29 Chapter 7. References 53 | |
| dc.language.iso | en | |
| dc.subject | Lon蛋白酶 | zh_TW |
| dc.subject | 地塞米松 | zh_TW |
| dc.subject | 調節型樹突細胞 | zh_TW |
| dc.subject | Regulatory dendritic cells | en |
| dc.subject | Dexamethasone | en |
| dc.subject | Lon protease | en |
| dc.title | 探討Lon蛋白酶在地塞米松誘導調節型樹突細胞之角色 | zh_TW |
| dc.title | Study the Role of Lon Protease in the Dexamethasone-induced Regulatory Dendritic Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李岳倫(Alan Yueh-Luen Lee),陳俊任(Chun-Jen Chen) | |
| dc.subject.keyword | Lon蛋白酶,調節型樹突細胞,地塞米松, | zh_TW |
| dc.subject.keyword | Lon protease,Regulatory dendritic cells,Dexamethasone, | en |
| dc.relation.page | 58 | |
| dc.identifier.doi | 10.6342/NTU202001964 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-07-29 | |
| 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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