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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 顧家綺(Chia-Chi Ku) | |
dc.contributor.author | Yun Chien | en |
dc.contributor.author | 簡筠 | zh_TW |
dc.date.accessioned | 2021-06-16T09:41:36Z | - |
dc.date.available | 2027-02-06 | |
dc.date.copyright | 2017-03-01 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-02-06 | |
dc.identifier.citation | 1. Ahmad, A., Sharif-Askari, E., Fawaz, L., and Menezes, J. (2000). Innate immune response of the human host to exposure with herpes simplex virus type 1: in vitro control of the virus infection by enhanced natural killer activity via interleukin-15 induction. J Virol 74, 7196-7203.
2. Akhtar, J., and Shukla, D. (2009). Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry. The FEBS journal 276, 7228-7236. 3. Chirifu, M., Hayashi, C., Nakamura, T., Toma, S., Shuto, T., Kai, H., Yamagata, Y., Davis, S.J., and Ikemizu, S. (2007). Crystal structure of the IL-15-IL-15Ralpha complex, a cytokine-receptor unit presented in trans. Nat Immunol 8, 1001-1007. 4. Di Meglio, P., Perera, G.K., and Nestle, F.O. (2011). The multitasking organ: recent insights into skin immune function. Immunity 35, 857-869. 5. Effendy, I., Loffler, H., and Maibach, H.I. (2000). Epidermal cytokines in murine cutaneous irritant responses. Journal of applied toxicology : JAT 20, 335-341. 6. Fehniger, T.A., and Caligiuri, M.A. (2001). Interleukin 15: biology and relevance to human disease. Blood 97, 14-32. 7. Freedberg, I.M., Tomic-Canic, M., Komine, M., and Blumenberg, M. (2001). Keratins and the keratinocyte activation cycle. The Journal of investigative dermatology 116, 633-640. 8. Geiss, G.K., Bumgarner, R.E., Birditt, B., Dahl, T., Dowidar, N., Dunaway, D.L., Fell, H.P., Ferree, S., George, R.D., Grogan, T., et al. (2008). Direct multiplexed measurement of gene expression with color-coded probe pairs. Nature biotechnology 26, 317-325. 9. Grabstein, K.H., Eisenman, J., Shanebeck, K., Rauch, C., Srinivasan, S., Fung, V., Beers, C., Richardson, J., Schoenborn, M.A., Ahdieh, M., and et al. (1994). Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264, 965-968. 10. Gutowska-Owsiak, D., and Ogg, G.S. (2012). The epidermis as an adjuvant. The Journal of investigative dermatology 132, 940-948. 11. Hotelling, H. (1933). Analysis of a complex of statistical variables into principal components. Journal of educational psychology 24, 417. 12. Kennedy-Crispin, M., Billick, E., Mitsui, H., Gulati, N., Fujita, H., Gilleaudeau, P., Sullivan-Whalen, M., Johnson-Huang, L.M., Suarez-Farinas, M., and Krueger, J.G. (2012). Human keratinocytes' response to injury upregulates CCL20 and other genes linking innate and adaptive immunity. The Journal of investigative dermatology 132, 105-113. 13. Kobayashi, H., Carrasquillo, J.A., Paik, C.H., Waldmann, T.A., and Tagaya, Y. (2000). Differences of biodistribution, pharmacokinetics, and tumor targeting between interleukins 2 and 15. Cancer Res 60, 3577-3583. 14. Lapaque, N., Walzer, T., Meresse, S., Vivier, E., and Trowsdale, J. (2009). Interactions between human NK cells and macrophages in response to Salmonella infection. Journal of immunology (Baltimore, Md. : 1950) 182, 4339-4348. 15. Le Borgne, M., Etchart, N., Goubier, A., Lira, S.A., Sirard, J.C., van Rooijen, N., Caux, C., Ait-Yahia, S., Vicari, A., Kaiserlian, D., and Dubois, B. (2006). Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo. Immunity 24, 191-201. 16. Lee, T.L., Chang, M.L., Lin, Y.J., Tsai, M.H., Chang, Y.H., Chuang, C.M., Chien, Y., Sosinowski, T., Wang, C.H., Chen, Y.Y., et al. (2015). An alternatively spliced IL-15 isoform modulates abrasion-induced keratinocyte activation. The Journal of investigative dermatology 135, 1329-1337. 17. Mishra, A., Sullivan, L., and Caligiuri, M.A. (2014). Molecular pathways: interleukin-15 signaling in health and in cancer. Clin Cancer Res 20, 2044-2050. 18. Musso, T., Calosso, L., Zucca, M., Millesimo, M., Ravarino, D., Giovarelli, M., Malavasi, F., Ponzi, A.N., Paus, R., and Bulfone-Paus, S. (1999). Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15. Blood 93, 3531-3539. 19. Pagliari, D., Cianci, R., Frosali, S., Landolfi, R., Cammarota, G., Newton, E.E., and Pandolfi, F. (2013). The role of IL-15 in gastrointestinal diseases: a bridge between innate and adaptive immune response. Cytokine & growth factor reviews 24, 455-466. 20. Perera, L.P., Goldman, C.K., and Waldmann, T.A. (1999). IL-15 induces the expression of chemokines and their receptors in T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 162, 2606-2612. 21. Shenoy, A.R., Kirschnek, S., and Hacker, G. (2014). IL-15 regulates Bcl-2 family members Bim and Mcl-1 through JAK/STAT and PI3K/AKT pathways in T cells. European journal of immunology 44, 2500-2507. 22. Tan, X., and Lefrancois, L. (2006). Novel IL-15 isoforms generated by alternative splicing are expressed in the intestinal epithelium. Genes Immun 7, 407-416. 23. Verri, W.A., Jr., Cunha, T.M., Ferreira, S.H., Wei, X., Leung, B.P., Fraser, A., McInnes, I.B., Liew, F.Y., and Cunha, F.Q. (2007). IL-15 mediates antigen-induced neutrophil migration by triggering IL-18 production. European journal of immunology 37, 3373-3380. 24. Yano, S., Komine, M., Fujimoto, M., Okochi, H., and Tamaki, K. (2003). Interleukin 15 induces the signals of epidermal proliferation through ERK and PI 3-kinase in a human epidermal keratinocyte cell line, HaCaT. Biochemical and biophysical research communications 301, 841-847. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59857 | - |
dc.description.abstract | 第15號細胞激素(IL-15)具有維持記憶性CD8、自然殺手以及自然殺手T 細胞的發育和細胞數恆定的功能。IL-15 同時也具有驅化免疫細胞、血管新生以及增強發炎激素生成的作用。更多的證據指出組織中表現過量的IL-15與多種人類發炎疾病與癌化的相關。過去本實驗室的研究結果發現,正常小鼠體內除了表現IL-15之外,同時也能表現極低量的異構體IL-15。由於表現該異構體IL-15的ENU突變鼠,發生記憶性CD8細胞缺失的結果,我們將該異構體IL-15命名為DM-IL-15。經過表現DM-IL-15 DNA質體的小鼠皮膚,對於引起皮膚發炎的各式刺激例如:機械性刮擦、化學物質刺激或是免疫製劑處理都比未處理組皮膚呈現較不敏感的反應。這些反應包括皮層細胞增生程度、細胞趨化激素表現量(CXCL-1, G-CSF)以及嗜中性白血球浸潤數目等比正常鼠均顯著地降低。從HSV-1感染後第二天、第五天小鼠皮膚外觀的變化可以看到DM-IL-15會擴大病灶的範圍,且延遲傷口癒合的時間。從皮膚組織病理分析的結果可以看到直到HSV-1感染後第五天仍有浸潤細胞的存在,顯示仍有新的皮膚細胞因病毒感染而延長發炎反應。這可能都與HSV-1感染初期DM-IL-15使宿主免疫反應不夠活化造成的。
為了更深入了解DM-IL-15對於小鼠皮膚在HSV-1感染後引起的免疫反應所受到的影響,我們將表現DM-IL-15 DNA質體的小鼠皮膚,經過HSV-1 感染後,檢測179個與發炎反應相關基因的表現與未處理組的皮膚相比較。實驗結果發現:表現DM-IL-15的皮膚受HSV-1感染後,促進MAPK訊息傳遞鏈中的激酶蛋白(kinase)表現的基因包括Mapk14、Mapk8、Map2k6,其表現量明顯高於未表現DM-IL-15對照組皮膚。同時TLR中的受體蛋白(receptor)基因Tlr7,也是在表現DM-IL-15的皮膚中有更多的表現量。以上的大部分的基因會在表皮細胞表現,也都與NF-κB的訊息傳遞鏈有關連,顯示DM-IL-15可能藉由調控表皮細胞中的NF-κB活化路徑,使宿主細胞受到壓力(cell stress)時走向DNA修復等功能的路徑;除此之外,DM-IL-15轉染的皮膚會增加pERK、pp38、pJNK的表現量,顯示可能會有與對照組不同的抗HSV-1的策略。未來的研究方向將著重於DM-IL-15對NF-κB路徑與機制的影響。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-06-16T09:41:36Z (GMT). No. of bitstreams: 1 ntu-106-R02449010-1.pdf: 2233935 bytes, checksum: b1b9060051485e97de8c0d1bbf828d97 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 口試委員會審定書………………………………………………………………………………………… x
誌謝………………………………………………………………………………………………....................... 2 中文摘要……………………………………………………………………………………………………….. 3 英文摘要……………………………………………………………………………………………………… 5 第一章 文獻探討………………………………………………………………….. 7 第二章 實驗方法與材料………………………………………………………………….. 18 第三章 實驗結果………………………………………………………………….. 24 第四章 結論與討論………………………………………………………………….. 34 第五章 圖與表………………………………………………………………….. 37 第六章 參考文獻………………………………………………………………….. 53 | |
dc.language.iso | zh-TW | |
dc.title | IL-15異構蛋白調控小鼠皮膚抗HSV-1免疫反應的研究 | zh_TW |
dc.title | Modulation of anti-HSV-1 immune responses in mouse skin by IL-15 alternatively spliced isoform | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 伍安怡(Betty Wu-Hsieh),李建國(Chien-Kuo Lee) | |
dc.subject.keyword | 介白質15,第一型?疹病毒,角質細胞, | zh_TW |
dc.subject.keyword | IL-15,HSV-1,keratinocytes, | en |
dc.relation.page | 55 | |
dc.identifier.doi | 10.6342/NTU201700366 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-02-06 | |
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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