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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄭景暉 | |
dc.contributor.author | Szu-I Lin | en |
dc.contributor.author | 林思儀 | zh_TW |
dc.date.accessioned | 2021-06-15T11:13:06Z | - |
dc.date.available | 2019-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-20 | |
dc.identifier.citation | Adcock IM, Chung KF, Caramori G, Ito K (2006). Kinase inhibitors and airway inflammation. European journal of pharmacology 533(1-3):118-132.
Akira S, Takeda K. 2004. Toll-like receptor signalling. Nat Rev Immunol. 4(7):499-511. Artlett CM (2013). Inflammasomes in wound healing and fibrosis. The Journal of pathology 229(2):157-167. Barkhordar RA, Ghani QP, Russell TR, Hussain MZ (2002). Interleukin-1beta activity and collagen synthesis in human dental pulp fibroblasts. Journal of endodontics 28(3):157-159. Brandt E, Petersen F, Flad HD (1992). Recombinant tumor necrosis factor-alpha potentiates neutrophil degranulation in response to host defense cytokines neutrophil-activating peptide 2 and IL-8 by modulating intracellular cyclic AMP levels. Journal of immunology (Baltimore, Md : 1950) 149(4):1356-1364. Brikos C, Wait R, Begum S, O'Neill LA, Saklatvala J (2007). Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88, and IRAK-4 as the stable components. Molecular & cellular proteomics : MCP 6(9):1551-1559. Cao Z, Henzel WJ, Gao X (1996a). IRAK: a kinase associated with the interleukin-1 receptor. Science (New York, NY) 271(5252):1128-1131. Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (1996b). TRAF6 is a signal transducer for interleukin-1. Nature 383(6599):443-446. Casadio R, Frigimelica E, Bossu P, Neumann D, Martin MU, Tagliabue A et al. (2001). Model of interaction of the IL-1 receptor accessory protein IL-1RAcP with the IL-1beta/IL-1R(I) complex. FEBS letters 499(1-2):65-68. Chang MC, Tsai YL, Chang HH, Lee SY, Lee MS, Chang CW et al. (2016). IL-1beta-induced MCP-1 expression and secretion of human dental pulp cells is related to TAK1, MEK/ERK, and PI3K/Akt signaling pathways. Archives of oral biology 61(16-22. Cheung PC, Campbell DG, Nebreda AR, Cohen P (2003). Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha. The EMBO journal 22(21):5793-5805. Culver C, Sundqvist A, Mudie S, Melvin A, Xirodimas D, Rocha S. 2010. Mechanism of hypoxia-induced nf-kappab. Molecular and cellular biology. 30(20):4901-4921. Deng L, Wang C, Spencer E, Yang L, Braun A, You J et al. (2000). Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103(2):351-361. Dinarello CA (1992). The role of interleukin-1 in host responses to infectious diseases. Infectious agents and disease 1(5):227-236. Dinarello CA (1996). Biologic basis for interleukin-1 in disease. Blood 87(6):2095-2147. Dou H, Song Y, Liu X, Yang L, Jiang N, Chen D et al. (2014). A novel benzenediamine derivate rescued mice from experimental sepsis by attenuating proinflammatory mediators via IRAK4. American journal of respiratory cell and molecular biology 51(2):191-200. Feinstein E, Kimchi A, Wallach D, Boldin M, Varfolomeev E. 1995. The death domain: A module shared by proteins with diverse cellular functions. Trends in biochemical sciences. 20(9):342-344. Fraczek J, Kim TW, Xiao H, Yao J, Wen Q, Li Y, Casanova JL, Pryjma J, Li X. 2008. The kinase activity of il-1 receptor-associated kinase 4 is required for interleukin-1 receptor/toll-like receptor-induced tak1-dependent nfkappab activation. The Journal of biological chemistry. 283(46):31697-31705. Hinz M, Stilmann M, Arslan SC, Khanna KK, Dittmar G, Scheidereit C. 2010. A cytoplasmic atm-traf6-ciap1 module links nuclear DNA damage signaling to ubiquitin-mediated nf-kappab activation. Molecular cell. 40(1):63-74. Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B et al. (1988). Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. European journal of immunology 18(11):1797-1801. Hoffmann E, Dittrich-Breiholz O, Holtmann H, Kracht M (2002). Multiple control of interleukin-8 gene expression. Journal of leukocyte biology 72(5):847-855. Holzberg D, Knight CG, Dittrich-Breiholz O, Schneider H, Dorrie A, Hoffmann E et al. (2003). Disruption of the c-JUN-JNK complex by a cell-permeable peptide containing the c-JUN delta domain induces apoptosis and affects a distinct set of interleukin-1-induced inflammatory genes. The Journal of biological chemistry 278(41):40213-40223. Hosoya S, Matsushima K, Ohbayashi E, Yamazaki M, Shibata Y, Abiko Y (1996). Stimulation of interleukin-1beta-independent interleukin-6 production in human dental pulp cells by lipopolysaccharide. Biochemical and molecular medicine 59(2):138-143. Huang GT, Potente AP, Kim JW, Chugal N, Zhang X (1999). Increased interleukin-8 expression in inflamed human dental pulps. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics 88(2):214-220. Inokuchi S, Aoyama T, Miura K, Osterreicher CH, Kodama Y, Miyai K et al. (2010). Disruption of TAK1 in hepatocytes causes hepatic injury, inflammation, fibrosis, and carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 107(2):844-849. Jiang Y, Russell TR, Schilder H, Graves DT (1998). Endodontic pathogens stimulate monocyte chemoattractant protein-1 and interleukin-8 in mononuclear cells. Journal of endodontics 24(2):86-90. Kajino-Sakamoto R, Inagaki M, Lippert E, Akira S, Robine S, Matsumoto K et al. (2008). Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis. Journal of immunology (Baltimore, Md : 1950) 181(2):1143-1152. Kellesarian SV, Al-Kheraif AA, Vohra F, Ghanem A, Malmstrom H, Romanos GE et al. (2016). Cytokine profile in the synovial fluid of patients with temporomandibular joint disorders: A systematic review. Cytokine 77(98-106. Keyel PA (2014). How is inflammation initiated? Individual influences of IL-1, IL-18 and HMGB1. Cytokine 69(1):136-145. Kollewe C, Mackensen AC, Neumann D, Knop J, Cao P, Li S, Wesche H, Martin MU. 2004. Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. The Journal of biological chemistry. 279(7):5227-5236. Kondo M, Tahara A, Hayashi K, Abe M, Inami H, Ishikawa T et al. (2014). Renoprotective effects of novel interleukin-1 receptor-associated kinase 4 inhibitor AS2444697 through anti-inflammatory action in 5/6 nephrectomized rats. Naunyn-Schmiedeberg's archives of pharmacology 387(10):909-919. Lamkanfi M, Dixit VM (2012). Inflammasomes and their roles in health and disease. Annual review of cell and developmental biology 28(137-161. Lamkanfi M, Dixit VM (2014). Mechanisms and functions of inflammasomes. Cell 157(5):1013-1022. Lertchirakarn V, Birner R, Messer HH (1998). Effects of interleukin-1 beta on human pulpal fibroblast proliferation and collagen synthesis. Journal of endodontics 24(6):409-413. Li S, Strelow A, Fontana EJ, Wesche H. 2002. Irak-4: A novel member of the irak family with the properties of an irak-kinase. Proceedings of the National Academy of Sciences of the United States of America. 99(8):5567-5572. Liu HH, Xie M, Schneider MD, Chen ZJ. 2006. Essential role of tak1 in thymocyte development and activation. Proceedings of the National Academy of Sciences of the United States of America. 103(31):11677-11682. Ma FY, Tesch GH, Ozols E, Xie M, Schneider MD, Nikolic-Paterson DJ (2011). TGF-beta1-activated kinase-1 regulates inflammation and fibrosis in the obstructed kidney. American journal of physiology Renal physiology 300(6):F1410-1421. Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA et al. (2002). Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. The Journal of clinical investigation 110(6):851-860. Muzio M, Natoli G, Saccani S, Levrero M, Mantovani A (1998). The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). The Journal of experimental medicine 187(12):2097-2101. Nakao S, Ogata Y, Shimizu-Sasaki E, Yamazaki M, Furuyama S, Sugiya H (2000). Activation of NFkappaB is necessary for IL-1beta-induced cyclooxygenase-2 (COX-2) expression in human gingival fibroblasts. Molecular and cellular biochemistry 209(1-2):113-118. Neubert M, Ridder DA, Bargiotas P, Akira S, Schwaninger M (2011). Acute inhibition of TAK1 protects against neuronal death in cerebral ischemia. Cell death and differentiation 18(9):1521-1530. Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J et al. (2008). Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. Cell 134(4):668-678. Ning L, Ishijima M, Kaneko H, Kurihara H, Arikawa-Hirasawa E, Kubota M et al. (2011). Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis. International orthopaedics 35(6):831-838. Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (1999). The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398(6724):252-256. Omori E, Matsumoto K, Sanjo H, Sato S, Akira S, Smart RC et al. (2006). TAK1 is a master regulator of epidermal homeostasis involving skin inflammation and apoptosis. The Journal of biological chemistry 281(28):19610-19617. Osuka A, Hanschen M, Stoecklein V, Lederer JA (2012). A protective role for inflammasome activation following injury. Shock (Augusta, Ga) 37(1):47-55. Papadakos KS, Sougleri IS, Mentis AF, Hatziloukas E, Sgouras DN (2013). Presence of terminal EPIYA phosphorylation motifs in Helicobacter pylori CagA contributes to IL-8 secretion, irrespective of the number of repeats. PloS one 8(2):e56291. Saccani S, Pantano S, Natoli G (2002). p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nature immunology 3(1):69-75. Sakurai H, Shigemori N, Hasegawa K, Sugita T (1998). TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism. Biochemical and biophysical research communications 243(2):545-549. Shirakabe K, Yamaguchi K, Shibuya H, Irie K, Matsuda S, Moriguchi T, Gotoh Y, Matsumoto K, Nishida E. 1997. Tak1 mediates the ceramide signaling to stress-activated protein kinase/c-jun n-terminal kinase. The Journal of biological chemistry. 272(13):8141-8144. Silva AC, Faria MR, Fontes A, Campos MS, Cavalcanti BN (2009). Interleukin-1 beta and interleukin-8 in healthy and inflamed dental pulps. Journal of applied oral science : revista FOB 17(5):527-532. Simpson RJ, Hammacher A, Smith DK, Matthews JM, Ward LD (1997). Interleukin-6: structure-function relationships. Protein science : a publication of the Protein Society 6(5):929-955. Soares DG, Basso FG, Scheffel DS, Hebling J, de Souza Costa CA (2015). Responses of human dental pulp cells after application of a low-concentration bleaching gel to enamel. Archives of oral biology 60(9):1428-1436. Song KW, Talamas FX, Suttmann RT, Olson PS, Barnett JW, Lee SW et al. (2009). The kinase activities of interleukin-1 receptor associated kinase (IRAK)-1 and 4 are redundant in the control of inflammatory cytokine expression in human cells. Molecular immunology 46(7):1458-1466. Stadler AF, Angst PD, Arce RM, Gomes SC, Oppermann RV, Susin C (2016). Gingival crevicular fluid levels of cytokines/chemokines in chronic periodontitis: a meta-analysis. Journal of clinical periodontology. Suarez-Fueyo A, Rojas JM, Cariaga AE, Garcia E, Steiner BH, Barber DF et al. (2014). Inhibition of PI3Kdelta reduces kidney infiltration by macrophages and ameliorates systemic lupus in the mouse. Journal of immunology (Baltimore, Md : 1950) 193(2):544-554. Thomay AA, Daley JM, Sabo E, Worth PJ, Shelton LJ, Harty MW et al. (2009). Disruption of interleukin-1 signaling improves the quality of wound healing. The American journal of pathology 174(6):2129-2136. Tokuhira N, Kitagishi Y, Suzuki M, Minami A, Nakanishi A, Ono Y et al. (2015). PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy (Review). International journal of molecular medicine 35(1):10-16. Trubiani O, Cataldi A, De Angelis F, D'Arcangelo C, Caputi S (2012). Overexpression of interleukin-6 and -8, cell growth inhibition and morphological changes in 2-hydroxyethyl methacrylate-treated human dental pulp mesenchymal stem cells. International endodontic journal 45(1):19-25. van Dijk EM, Menzen MH, Spanjer AI, Middag LD, Brandsma CA, Gosens R (2016). Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts. American journal of physiology Lung cellular and molecular physiology 310(11):L1166-1176. Waage A, Brandtzaeg P, Halstensen A, Kierulf P, Espevik T (1989). The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. The Journal of experimental medicine 169(1):333-338. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001). TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412(6844):346-351. Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z (1997). MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7(6):837-847. Wu ZH, Wong ET, Shi Y, Niu J, Chen Z, Miyamoto S, Tergaonkar V. 2010. Atm- and nemo-dependent elks ubiquitination coordinates tak1-mediated ikk activation in response to genotoxic stress. Molecular cell. 40(1):75-86. Yang L, Inokuchi S, Roh YS, Song J, Loomba R, Park EJ et al. (2013). Transforming growth factor-beta signaling in hepatocytes promotes hepatic fibrosis and carcinogenesis in mice with hepatocyte-specific deletion of TAK1. Gastroenterology 144(5):1042-1054.e1044. Zhang D, Yan H, Li H, Hao S, Zhuang Z, Liu M et al. (2015). TGFbeta-activated Kinase 1 (TAK1) Inhibition by 5Z-7-Oxozeaenol Attenuates Early Brain Injury after Experimental Subarachnoid Hemorrhage. The Journal of biological chemistry 290(32):19900-19909. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48989 | - |
dc.description.abstract | 在牙髓的急性及慢性發炎中,Interleukin 1 β (IL-1β)為一常見的促炎性細胞因子,而IL-6和IL-8則是其下游的發炎因子。近年來在IL-1β的細胞訊息路徑中有兩個重要的訊息分子transforming growth factor β-activated kinase-1 (TAK1)和interleukin-1 receptor-associated kinases (IRAKs)被發現,後續亦有研究探討其應用於治療發炎性疾病的可能性,然而這兩個訊息因子對於牙髓細胞中Interleukin 1 β (IL-1β)促進IL-6及IL-8表現及分泌的影響目前並不清楚
實驗設計:將培養皿中的人類牙髓細胞分成不同的組別,分別經過5z-7-oxozeaenol (TAK1抑制劑)或IRAK1/4抑制劑處理後,暴露於含有Interleukin 1 β (IL-1β)的細胞培養液中。細胞會進行3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT)實驗已確定所加入的藥劑不會造成細胞死亡,之後藉由螢光染色來觀察TAK1和IRAKs磷酸化的情形,以西方墨點法來檢測IL-6和IL-8分泌的情形,以RT-PCR來檢測IL-6和IL-8的mRNA表現,並且以ELISA定量IL-8的分泌狀況。 實驗結果:牙髓細胞在經過IL-1β (0.1-10 ng/ml)刺激後可以觀察到IL-6及IL-8的表現明顯增加,此外也可以觀察到IRAK1和TAK1有磷酸化的情形。細胞在經過低於毒性濃度的5z-7-oxozeaenol (1 and 2.5 μM)和IRAK1/4抑制劑(10, 20 and 40 μM)的處理後,可以觀察到IL-6和IL-8的表現受到了抑制。 結論:實驗的結果證實IL-1β可以藉由促進IL-6和IL-8的分泌來調控牙髓細胞的發炎反應和修復,而其中的調控與TAK1和IRAKs有關,抑制TAK1或是IRAKs或許可以成為將來調控牙髓發炎反應及修復的方法。 | zh_TW |
dc.description.abstract | Objective: Interleukin 1 β (IL-1β) is a pro-inflammatory cytokine involved in the acute and chronic inflammatory processes of dental pulp. IL-6 and IL-8 are two inflammatory mediators. However, the role of transforming growth factor β-activated kinase-1 (TAK1) and interleukin-1 receptor-associated kinases (IRAKs) in responsible for the effects of IL-1β on the IL-6 and IL-8 expression/secretion of dental pulp cells are not clear. Design: Human dental pulp cells were exposed to IL-1β with/without pretreatment with 5z-7-oxozeaneaeol (a TAK1 inhibitor) or IRAK1/4 inhibitor. The 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay was performed to estimate the viable cell number. The expression of p-TAK1 and p-IRAK1 were observed by immunofluorescence. The protein expression of IL-6 and IL-8 was tested by western blot and the expression of IL-6 and IL-8 mRNA was studied by reverse transcriptase-polymerase chain reaction (RT-PCR). The secretion of IL-8 was measured by enzyme-linked immunosorbant assay. Results: Exposure of dental pulp cells to IL-1β (0.1-10 ng/ml) stimulated the IL-6 and IL-8 expression and secretion by dental pulp cells. The phosphorylation of TAK1 and IRAK1 can also be observed after exposed dental pulp cells to IL-1β. Pretreatment and co-incubation of pulp cells by 5z-7oxozeaenol (1 and 2.5 μM) and IRAK1/4 inhibitor (10, 20 and 40 μM) at non-toxic concentrations could prevent the IL-1β-induced IL-6 and IL-8 expression. 5z-7oxozeaenol and IRAK1/4 also attenuated the IL-1β-induced IL-6 and IL-8 secretion of dental pulp cells. Conclusions: These results indicate that IL-1β can be important in the pathogenesis of pulpal inflammatory diseases and repair via stimulation of IL-6 and IL-8 expression and secretion. These events are associated with TAK1 and IRAK1/4 signaling pathways of dental pulp cells. Blocking of TAK1 and IRAK1/4 may have potential use to control inflammation of dental pulp in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T11:13:06Z (GMT). No. of bitstreams: 1 ntu-105-R02422008-1.pdf: 2194765 bytes, checksum: 1427a67c9bc0c5ea73ac6e384b22b422 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 中文摘要………………………………………………………………………………3
English Abstract……………………………………………………………………...4 Abbreviation………………………………………………………………………….5 表目錄…………………………………………………………………………………6 圖目錄…………………………………………………………………………………7 1. Literature review 1.1 Role of IL-1β in inflammation and repair processes………………………8 1.2 IL-1β, IL-6 and IL-8 activity in human dental pulp cells……..…………..9 1.3 IL-1β signaling pathway…………………..………………………………..10 1.4 Update of TAK1 and IRAKs……………………………………………….11 1.5 Targeting of TAK1 and IRAKs as therapeutic intervention of inflammatory disease……………...………………………………………..12 1.6 Question Remain & Hypothesis….………………………………………...13 2. Materials and Methods 2.1 Materials…………………...………………………………………………..14 2.2 Culture of human dental pulp cells………………………….……………..14 2.3 MTT assay………………………………….………………………………..15 2.4 Effect of IL-1β on IRAK, pIRAK, pTAK1, IL-8 protein expression of pulp cells...................................................................................................................15 2.5 Expression of IL-6 and IL-8 in human dental pulp cell and its regulation by IL-1β...........................................................................................................18 2.6 Effect of IL-1β on pIRAK, pTAK1 protein expression of pulp cells…….21 2.7 Effects of IL-1β with/without Inhibitors on the Cytotoxicity and Generation of IL-6, IL-8 in Dental Pulp Cells ……………………..….….22 2.8 Statistical Analysis……………………………………………………….….23 3. Results……………………………………………………………………….…..24 4. Discussions………………………………………………………………………26 5. Conclusions………...……………………………………………………………28 6. References……………………………………………………………………….29 7. 附錄……………….…………………………………….………………………..37 | |
dc.language.iso | en | |
dc.title | IL-1β對人類牙髓細胞表現及分泌細胞激素
IL-6和IL-8的影響:TAK1和IRAKs的角色 | zh_TW |
dc.title | Effect of IL-1β on IL6 and IL-8
Expression/production in Dental Pulp Cells: Role of TAK1 and IRAKs | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 張曉華 | |
dc.contributor.oralexamcommittee | 張美姬,張育超,謝義興 | |
dc.subject.keyword | IL-1β,人類牙髓細胞,牙髓發炎,訊息路徑,TAK1,IRAKs,IL-6,IL-8, | zh_TW |
dc.subject.keyword | IL-1β,human dental pulp cell,pulpal inflammation,Signal transduction,TAK1,IRAKs,IL-6,IL-8, | en |
dc.relation.page | 54 | |
dc.identifier.doi | 10.6342/NTU201602856 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
顯示於系所單位: | 臨床牙醫學研究所 |
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