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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡欣祐(Hsin-Yue Tsai) | |
| dc.contributor.author | Tianyi-Yi Lim | en |
| dc.contributor.author | 林恬伊 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:55:05Z | - |
| dc.date.copyright | 2020-08-27 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-18 | |
| dc.identifier.citation | Aartsen, M.G., Ackermann, M., Adams, J., Aguilar, J.A., Ahlers, M., Ahrens, M., Altmann, D., Anderson, T., Arguelles, C., Arlen, T.C., et al. (2014). Observation of high-energy astrophysical neutrinos in three years of IceCube data. Phys Rev Lett 113, 101101. Almanza, A., Carlesso, A., Chintha, C., Creedican, S., Doultsinos, D., Leuzzi, B., Luis, A., McCarthy, N., Montibeller, L., More, S., et al. (2019). Endoplasmic reticulum stress signalling - from basic mechanisms to clinical applications. FEBS J 286, 241-278. Ayaub, E.A., Tandon, K., Padwal, M., Imani, J., Patel, H., Dubey, A., Mekhael, O., Upagupta, C., Ayoub, A., Dvorkin-Gheva, A., et al. (2019). IL-6 mediates ER expansion during hyperpolarization of alternatively activated macrophages. Immunol Cell Biol 97, 203-217. Bo Shan, Xiaoxia Wang, and Liu, Y. (2017). The metabolic ER stress sensor IRE1 suppresses alternative activation of macrophages and impairs energy expenditure in obesity. nature immunology 18, 519–529. Cao, J., Dong, R., Jiang, L., Gong, Y., Yuan, M., You, J., Meng, W., Chen, Z., Zhang, N., Weng, Q., et al. (2019). LncRNA-MM2P Identified as a Modulator of Macrophage M2 Polarization. Cancer Immunol Res 7, 292-305. Diaz-Bulnes, P., Saiz, M.L., Lopez-Larrea, C., and Rodriguez, R.M. (2019). Crosstalk Between Hypoxia and ER Stress Response: A Key Regulator of Macrophage Polarization. Front Immunol 10, 2951. Freemerman, A.J., Johnson, A.R., Sacks, G.N., Milner, J.J., Kirk, E.L., Troester, M.A., Macintyre, A.N., Goraksha-Hicks, P., Rathmell, J.C., and Makowski, L. (2014). Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype. J Biol Chem 289, 7884-7896. Gao, Z., Li, Y., Wang, F., Huang, T., Fan, K., Zhang, Y., Zhong, J., Cao, Q., Chao, T., Jia, J., et al. (2017). Mitochondrial dynamics controls anti-tumour innate immunity by regulating CHIP-IRF1 axis stability. Nat Commun 8, 1805. Grootjans, J., Kaser, A., Kaufman, R.J., and Blumberg, R.S. (2016). The unfolded protein response in immunity and inflammation. Nat Rev Immunol 16, 469-484. He, C., and Carter, A.B. (2015). The Metabolic Prospective and Redox Regulation of Macrophage Polarization. J Clin Cell Immunol 6. He, C., Ryan, A.J., Murthy, S., and Carter, A.B. (2013). Accelerated development of pulmonary fibrosis via Cu,Zn-superoxide dismutase-induced alternative activation of macrophages. J Biol Chem 288, 20745-20757. Huang, S.C., Everts, B., Ivanova, Y., O'Sullivan, D., Nascimento, M., Smith, A.M., Beatty, W., Love-Gregory, L., Lam, W.Y., O'Neill, C.M., et al. (2014). Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol 15, 846-855. Iwasaki, Y., Suganami, T., Hachiya, R., Shirakawa, I., Kim-Saijo, M., Tanaka, M., Hamaguchi, M., Takai-Igarashi, T., Nakai, M., Miyamoto, Y., et al. (2014). Activating transcription factor 4 links metabolic stress to interleukin-6 expression in macrophages. Diabetes 63, 152-161. Izquierdo, E., Cuevas, V.D., Fernandez-Arroyo, S., Riera-Borrull, M., Orta-Zavalza, E., Joven, J., Rial, E., Corbi, A.L., and Escribese, M.M. (2015). Reshaping of Human Macrophage Polarization through Modulation of Glucose Catabolic Pathways. J Immunol 195, 2442-2451. Jan Van den Bossche, Jeroen Baardman, and Winther, M.P.J.d. (2016). Mitochondrial Dysfunction Prevents Repolarization of Inflammatory Macrophages. Cell Reports 17, 684–696. Jha, A.K., Huang, S.C., Sergushichev, A., Lampropoulou, V., Ivanova, Y., Loginicheva, E., Chmielewski, K., Stewart, K.M., Ashall, J., Everts, B., et al. (2015). Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42, 419-430. Kapoor, N., Niu, J., Saad, Y., Kumar, S., Sirakova, T., Becerra, E., Li, X., and Kolattukudy, P.E. (2015). Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP. J Immunol 194, 6011-6023. Lerner, A.G., Upton, J.P., Praveen, P.V., Ghosh, R., Nakagawa, Y., Igbaria, A., Shen, S., Nguyen, V., Backes, B.J., Heiman, M., et al. (2012). IRE1alpha induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab 16, 250-264. Li, Y., He, Y., Miao, K., Zheng, Y., Deng, C., and Liu, T.M. (2020). Imaging of macrophage mitochondria dynamics in vivo reveals cellular activation phenotype for diagnosis. Theranostics 10, 2897-2917. Liu, P.S., Wang, H., Li, X., Chao, T., Teav, T., Christen, S., Di Conza, G., Cheng, W.C., Chou, C.H., Vavakova, M., et al. (2017). alpha-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol 18, 985-994. Mantovani, A., Biswas, S.K., Galdiero, M.R., Sica, A., and Locati, M. (2013). Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 229, 176-185. Maurel, M., Chevet, E., Tavernier, J., and Gerlo, S. (2014). Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem Sci 39, 245-254. Michelucci, A., Cordes, T., Ghelfi, J., Pailot, A., Reiling, N., Goldmann, O., Binz, T., Wegner, A., Tallam, A., Rausell, A., et al. (2013). Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci U S A 110, 7820-7825. Mills, E.L., Kelly, B., Logan, A., Costa, A.S.H., Varma, M., Bryant, C.E., Tourlomousis, P., Dabritz, J.H.M., Gottlieb, E., Latorre, I., et al. (2016). Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell 167, 457-470 e413. Mosser, D.M., and Edwards, J.P. (2008). Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8, 958-969. Murphy, M.P. (2009). How mitochondria produce reactive oxygen species. Biochem J 417, 1-13. Ramirez, M.U., Hernandez, S.R., Soto-Pantoja, D.R., and Cook, K.L. (2019). Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response. Int J Mol Sci 21. Sirunyan, A.M., Tumasyan, A., Adam, W., Ambrogi, F., Bergauer, T., Brandstetter, J., Dragicevic, M., Ero, J., Escalante Del Valle, A., Flechl, M., et al. (2020). Mixed higher-order anisotropic flow and nonlinear response coefficients of charged particles in PbPb collisions at s NN = 2.76 and 5.02 TeV. Eur Phys J C Part Fields 80, 534. Soto-Pantoja, D.R., Wilson, A.S., Clear, K.Y., Westwood, B., Triozzi, P.L., and Cook, K.L. (2017). Unfolded protein response signaling impacts macrophage polarity to modulate breast cancer cell clearance and melanoma immune checkpoint therapy responsiveness. Oncotarget 8, 80545-80559. Tavakoli, S., Zamora, D., Ullevig, S., and Asmis, R. (2013). Bioenergetic profiles diverge during macrophage polarization: implications for the interpretation of 18F-FDG PET imaging of atherosclerosis. J Nucl Med 54, 1661-1667. Viola, A., Munari, F., Sanchez-Rodriguez, R., Scolaro, T., and Castegna, A. (2019). The Metabolic Signature of Macrophage Responses. Front Immunol 10, 1462. Wynn, T.A., Chawla, A., and Pollard, J.W. (2013). Macrophage biology in development, homeostasis and disease. Nature 496, 445-455. Yang, F., Liu, Y., Ren, H., Zhou, G., Yuan, X., and Shi, X. (2019). ER-stress regulates macrophage polarization through pancreatic EIF-2alpha kinase. Cell Immunol 336, 40-47. Yang, F., Wang, S., Liu, Y., Zhou, Y., Shang, L., Feng, M., Yuan, X., Zhu, W., and Shi, X. (2018). IRE1alpha aggravates ischemia reperfusion injury of fatty liver by regulating phenotypic transformation of kupffer cells. Free Radic Biol Med 124, 395-407. Zanluqui NG, Wowk PF, and P, P.-F. (2015). Macrophage Polarization in Chagas Disease. J Clin Cell Immunol 6, 317. Zhang, K., and Kaufman, R.J. (2008). From endoplasmic-reticulum stress to the inflammatory response. Nature 454, 455-462. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19354 | - |
| dc.description.abstract | 巨噬細胞是一個具有高度可塑性的先天性免疫細胞，在病原體防禦和組織修復的中扮演重要的角色。巨噬細胞在接受不同環境刺激後會活化為兩種不同的狀態： 促進發炎狀態(M1)或是抗發炎狀態(M2)。先前研究指出內質網壓力所產生的ER Unfolded protein response(ER-UPR，未摺疊蛋白反應)參與在巨噬細胞的活化過程中，但是目前對於內質網壓力如何影響巨噬細胞活化仍有爭議。同時，細胞內養份的代謝途徑也會因巨噬細胞的活化而改變。M1 巨噬細胞主要依賴糖解作用來產生能量，同時會阻斷檸檬酸循環；M2 巨噬細胞則會透過氧化脂肪酸來促進粒線體的呼吸作用進而產生能量。因此，本研究的目的是想要利用檢測粒腺體呼吸作用(mt-ROS)的活性來區分不同狀態的巨噬細胞，並且藉此來了解在ER-UPR失效的情況下粒線體呼吸作用的活性是否參與巨噬細胞活化。我們研究發現,M2 巨噬細胞相較於M0有較高的mt-ROS，則M1巨噬細胞有較的的mt-ROS。接著，在不朽化骨髓源性巨噬細胞(immortalized BMDMs) 基因敲弱(gene silenncing，基因沉默)來抑制UPR 途經中幾個重要的蛋白。希望在接下來的研究中，藉由這個系統可以讓我們釐清內質網壓力所產生的UPR會如何影響巨噬細胞活化以及粒線體呼吸作用。 | zh_TW |
| dc.description.abstract | Macrophages are high plasticity innate immune cells which are important for host defenses and maintain tissue homeostasis, by polarizing into two statuses; pro-inflammatory(M1) profile or anti-inflammatory(M2), respectively. Endoplasmic reticulum (ER) stress responses have been reported to participate in macrophage polarization. The regulation between ER stress responses and macrophage polarization is controversial, although they had been studied for a while. Moreover, the metabolic profile has also shown affected by macrophage polarization. For instance, M1 macrophage mainly produces energy by aerobic glycolysis but broken TAC cycle, whereas M2 macrophage prefers fatty acid oxidation(FAO) and oxidative phosphorylation(OXPHOS). Therefore, the goal for this study is to generate mitochondria detection system to distinguish naïve, M1 and M2 macrophage using the differences in their respiratory status and further examine whether there is a similar correlation between mitochondria respiratory status(mt-ROS) and macrophage polarity in ER-UPR defective system. In our finding, we had detected the strongest mt-ROS level in M2 macrophage follow by naïve and M1 macrophage. Then, we generated knocking down key protein in the major ER stress response pathway in immortalized bone marrow cell lines. Our ongoing data will help to clarify whether and how ER stress participates in macrophage polarization as well as their differential mtROS response. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:55:05Z (GMT). No. of bitstreams: 1 U0001-1708202011490600.pdf: 2985262 bytes, checksum: e457fd241165e8e4f04820a5ea724a1a (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | Acknowledgements i 中文摘要 ii Abstract iii Table of Contents v Chapter 1. Introduction 1 1.1 Overview of macrophage polarizations 1 1.2 The genetic and functional profile of macrophage polarizations 2 1.3 Unfolded protein responses(UPR) in the endoplasmic reticulum(ER) manipulate macrophage polarizations 4 1.4 Metabolic regulation of macrophage polarizations 8 Chapter 2 Materials and methods 11 2.1 Mice 11 2.2 Bone marrow-derived macrophages(BMDMs) 11 2.3 Immortalized bone marrow-derived macrophages(iBMDMs) 12 2.4 Cell culture conditions 13 2.5 MitoSOX staining and cell imaging 13 2.6 Mitotracker deep red FM staining 14 2.7 MitoSOX staining for Flow cytometry 14 2.8 RNA extraction and quantitation real time-PCR 15 2.9 Statistical analysis 16 Chapter 3. Result 17 3.1 BMDMs and immortalized BMDMs show distinct mitochondria ROS response between naïve macrophages and polarized macrophages 17 3.2 Examination of the quantity and quality of mitochondrial in Naïve, M1 and M2 BMDMs 19 3.3 BMDM showed low discrimination of MitoSOX examined by flow cytometry 20 3.4 Establish ER-UPR pathway knock down system in iBMs 21 3.5 M2 polarization is affected in iBMDMs-XBP1KD 22 Chapter 4 Discussion 24 4.1 The possibility of MitoSOX intensity for discrimination of naïve, M1 and M2 macrophages 24 4.2 XBP1 knock down in iBMDMs affected M2 polarization but not M1 polarization. 25 Chapter 5 Figures 26 Figure 1. MitoSOX staining analysis in BMDMs. 29 Figure 2. MitoSOX staining analysis in iBMDMs 32 Figure 3 Mitochondria quantity and function determination in various status macrophages 35 Figure 4 Flow cytometry analysis of MitoSOX intensity in BMDMs 37 Figure 5 ER-UPR pathway knock down- iBMs cell lines. 38 Figure 6 MitoSOX staining in iBMDMs-XBP1KD 41 Table 42 Table-Ⅰ primers for qRT-PCR. 42 References 43 | |
| dc.language.iso | en | |
| dc.title | 探討內質網壓力如何調控巨噬細胞及其粒線體呼吸作用 | zh_TW |
| dc.title | How ER stress modulates different macrophage polarization and their mitochondria status. | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 劉雅雯(Ya-Wen Liu),吳青錫(Ching-Shyi Wu),張壯榮(Chuang-Rung Chang) | |
| dc.subject.keyword | 巨噬細胞活化,內質網壓力,粒線體呼吸作用, | zh_TW |
| dc.subject.keyword | Macrophage polarization,ER stress response,Mitochondrial respiratory status, | en |
| dc.relation.page | 43 | |
| dc.identifier.doi | 10.6342/NTU202003707 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-08-18 | |
| 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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