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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳俊任 | |
| dc.contributor.author | Yu–Jing Zhuang | en |
| dc.contributor.author | 莊育菁 | zh_TW |
| dc.date.accessioned | 2021-06-15T01:26:23Z | - |
| dc.date.available | 2011-07-27 | |
| dc.date.copyright | 2009-07-27 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-07-23 | |
| dc.identifier.citation | 1. Lin, Z. B., and H. N. Zhang. 2004. Anti-tumor and immunoregulatory activities
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The inhibitory effect of the Chinese herb Ganoderma lucidum mycelium on gut immunoglobulin A responses to cholera toxin in mice. Nutrition Research 23:691–701. 15. Reinhardt, R. L., S. J. Kang, H. E. Liang, and R. M. Locksley. 2006. T helper cell effector fates--who, how and where? Curr Opin Immunol 18:271-277. 16. Zhu, J., and W. E. Paul. 2008. CD4 T cells: fates, functions, and faults. Blood 112:1557-1569. 17. Wilson, C. B., E. Rowell, and M. Sekimata. 2009. Epigenetic control of T-helper-cell differentiation. Nat Rev Immunol 9:91-105. 18. Hathcock, K. S., G. Laszlo, C. Pucillo, P. Linsley, and R. J. Hodes. 1994. Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. J Exp Med 180:631-640. 19. Angelin-Duclos, C., G. Cattoretti, K. I. Lin, and K. Calame. 2000. Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. J Immunol 165:5462-5471. 20. Trinchieri, G., and A. Sher. 2007. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol 7:179-190. 21. Liu, Y., E. G. Shepherd, and L. D. Nelin. 2007. MAPK phosphatases--regulating the immune response. Nat Rev Immunol 7:202-212. 22. Lee, M. S., and Y. J. Kim. 2007. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem 76:447-480. 23. Lin, J. M., C. C. Lin, M. F. Chen, T. Ujiie, and A. Takada. 1995. Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum. J Ethnopharmacol 47:33-41. 24. 陳明煦. 2006 台灣紫芝生物活性代謝產物之醱酵生產與功能評估. 國立台 灣大學微生物與生化學研究所碩士論文. 25. Lyons, A. B. 2000. Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J Immunol Methods 243:147-154. 26. Parish, C. R., M. H. Glidden, B. J. Quah, and H. S. Warren. 2009. Use of the intracellular fluorescent dye CFSE to monitor lymphocyte migration and proliferation. Curr Protoc Immunol Chapter 4:Unit4 9. 27. Hayden, M. S., and S. Ghosh. 2004. Signaling to NF-kappaB. Genes Dev 18:2195-2224. 28. Dal Porto, J. M., S. B. Gauld, K. T. Merrell, D. Mills, A. E. Pugh-Bernard, and J. Cambier. 2004. B cell antigen receptor signaling 101. Mol Immunol 41:599-613. 29. Fairfax, K. A., A. Kallies, S. L. Nutt, and D. M. Tarlinton. 2008. Plasma cell development: from B-cell subsets to long-term survival niches. Semin Immunol 20:49-58. 30. Kurosaki, T., and M. Hikida. 2009. Tyrosine kinases and their substrates in B lymphocytes. Immunol Rev 228:132-148. 31. Scapini, P., S. Pereira, H. Zhang, and C. A. Lowell. 2009. Multiple roles of Lyn kinase in myeloid cell signaling and function. Immunol Rev 228:23-40. 32. Brown, G. D., P. R. Taylor, D. M. Reid, J. A. Willment, D. L. Williams, L. Martinez-Pomares, S. Y. Wong, and S. Gordon. 2002. Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med 196:407-412. 33. Tsoni, S. V., and G. D. Brown. 2008. beta-Glucans and dectin-1. Ann N Y Acad Sci 1143:45-60. 34. Willment, J. A., and G. D. Brown. 2008. C-type lectin receptors in antifungal immunity. Trends Microbiol 16:27-32. 35. Taylor, P. R., G. D. Brown, D. M. Reid, J. A. Willment, L. Martinez-Pomares, S. Gordon, and S. Y. Wong. 2002. The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J Immunol 169:3876-3882. 36. Robinson, M. J., D. Sancho, E. C. Slack, S. LeibundGut-Landmann, and C. Reis e Sousa. 2006. Myeloid C-type lectins in innate immunity. Nat Immunol 7:1258-1265. 37. Chen, H. S., Y. F. Tsai, S. Lin, C. C. Lin, K. H. Khoo, C. H. Lin, and C. H. Wong. 2004. Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi) polysaccharides. Bioorg Med Chem 12:5595-5601. 38. Lin, K. I., Y. Y. Kao, H. K. Kuo, W. B. Yang, A. Chou, H. H. Lin, A. L. Yu, and C. H. Wong. 2006. Reishi polysaccharides induce immunoglobulin production through the TLR4/TLR2-mediated induction of transcription factor Blimp-1. J Biol Chem 281:24111-24123. 39. Han, S. B., S. H. Park, K. H. Lee, C. W. Lee, S. H. Lee, H. C. Kim, Y. S. Kim, H. S. Lee, and H. M. Kim. 2001. Polysaccharide isolated from the radix of Platycodon grandiflorum selectively activates B cells and macrophages but not T cells. Int Immunopharmacol 1:1969-1978. 40. Han, S. B., S. K. Park, H. J. Ahn, Y. D. Yoon, Y. H. Kim, J. J. Lee, K. H. Lee, J. S. Moon, H. C. Kim, and H. M. Kim. 2003. Characterization of B cell membrane receptors of polysaccharide isolated from the root of Acanthopanax koreanum. Int Immunopharmacol 3:683-691. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42860 | - |
| dc.description.abstract | 台灣紫芝 (Ganoderma formosanum) 為台灣本島特有靈芝品種，目前對於紫芝
的相關研究仍相當稀少且僅有一篇文獻研究台灣紫芝子實體熱水萃取物，其清除 自由基能力及護肝效果之評估。真菌細胞壁主成分中的多醣體主要由 β-glucans 構 成，已有許多研究指出 β-glucans 可以刺激免疫細胞。因此在本篇研究中，將探討 台灣紫芝多醣體 F2 是否能夠對脾臟淋巴細胞有免疫調節的能力。首先，我們發 現 F2 能刺激脾臟淋巴細胞的增生，且此活性不會因多黴素 (polymyxin B) 的處理 而受到影響，因此排除了樣品可能受到脂多醣 (LPS) 的汙染的機會。另外經蛋白 質水解酶 (protease K) 處理過之 F2 也仍保留刺激活性，顯示 F2 刺激脾臟淋巴細 胞的能力的確是來自於多醣體 (polysaccharides) 而非來自蛋白質。雖然實驗發 現 F2 無法直接刺激 CD4 T 淋巴球增生，但在 F2 刺激脾臟淋巴細胞時，可間接使 其中的 CD4 T 淋巴球產生 IFN-γ 而走向 Th1 免疫反應。除此之外，經由實驗發現 F2 可直接刺激 B 淋巴球的增生及增加早期活化抗原(CD69 及 CD86) 的表現及 M 型 免疫球蛋白 (IgM) 的產生，這些結果顯示出 F2 可誘導 B 淋巴球分化成 IgM 分泌 型的 B 淋巴球。最後實驗發現此 F2 所誘導 B 淋巴球產生 IgM 是透過 MAPK, NF-κB 及 Syk 路徑，但透過何種受體 (receptor) 及詳細的機制仍需更進一步的實驗證 實。 | zh_TW |
| dc.description.abstract | Ganoderma formosanum is a native species of Ganoderma sp. in Taiwan.
Until now, there has been only very few studies on this Ganoderma strain. The polysaccharides of fungal cell wall, which mainly consist of β-glucans moieties, have been reported to serve as microbial ligands that can stimulate pattern-recognition receptors on immune cells. A major polysaccharide fraction, F2, was purified from the submerged culture of G. formosanum, and in this study, we examined the immunomodulatory activity of F2 in mouse splenic lymphocytes. We found that F2 could stimulate the proliferation of splenocytes. Polymyxin B treatment did not significantly affect the activity of F2, excluding the possibility LPS contamination in our samples. Protease K-treated F2 still retained the stimulatory function, indicating that it was the polysaccharides, but not any protein component, that contributed to the stimulation of splenocytes. F2 could not stimulate splenic CD4 T lymphocyte proliferation directly; however it stimulated the production of IFN-γ, a Th1 cytokine, from CD4 T lymphocytes in the splenocyte culture. In contrast, F2 stimulated splenic B lymphocyte proliferation directly, and F2 stimulation increased the expression of early activation antigen (CD69 and CD86) and induced IgM production. Finally, our results indicated that MAPK (ERK, p38, JNK), NF-κB and Syk signaling pathways are involved in F2-stimulated IgM production in B lymphocytes. Further studies will be done to investigate the detailed mechanisms including specific receptor(s) on B lymphocytes that are activated by the polysaccharides of Ganoderma formosanum. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T01:26:23Z (GMT). No. of bitstreams: 1 ntu-98-R96b47105-1.pdf: 1005118 bytes, checksum: ab25210106cd7e547b7d7111bc67a6b6 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | CONTENTS
口試委員會審定書 ........................................................................................................... # 謝誌 ....................................................................................................................................i 中文摘要 .......................................................................................................................... ii ABSTRACT .................................................................................................................... iii CONTENTS .....................................................................................................................iv LIST OF FIGURES ........................................................................................................ vii LIST OF TABLES ............................................................................................................ix Chapter 1 Introduction .............................................................................................. 1 1.1 Ganoderma spp. (Lingzhi).............................................................................. 1 1.2 Immunostimulatory activity of Ganoderma polysaccharides ........................ 2 1.3 Effect of Ganoderma products on T and B lymphocytes ............................... 3 1.4 T lymphocyte activation and differentiation ................................................... 4 1.5 B lymphocyte activation and functions .......................................................... 6 1.6 Mitogen-activated protein kinases (MAPKs) and NF-κB activation ............. 7 1.7 Ganoderma formosanum ................................................................................ 9 1.8 Previous work on Ganoderma formosanum in this laboratory ....................... 9 1.9 Aims of this study ......................................................................................... 10 Chapter 2 Materials and Methods .......................................................................... 11 2.1 Animals ......................................................................................................... 11 2.2 F2 preparation ............................................................................................... 11 2.3 Preparation of splenocytes from mouse spleens ........................................... 12 2.4 Isolation of CD4 T lymphocytes and B lymphocytes from splenocytes ....... 12 2.5 Cell proliferation assay ................................................................................. 13 2.6 Analysis of the enlarged subpopulations of lymphocytes by flow cytometry13 2.7 RNA isolation and qRT-PCR ........................................................................ 14 2.8 Cytokine production analysis ....................................................................... 15 2.9 Analysis of B lymphocyte proliferation in vitro using CFSE ....................... 16 2.10 CD69 and CD86 activation analysis ............................................................. 16 2.11 IgM detection by ELISA .............................................................................. 17 2.12 CD138 expression analysis ........................................................................... 17 2.13 Analysis of MAPK, NF-κB and Syk activation by specific inhibitor .......... 18 2.14 MAPK activation .......................................................................................... 19 2.15 SDS-PAGE and Western blotting ................................................................. 19 2.16 Statistics ........................................................................................................ 20 Chapter 3 Results ..................................................................................................... 21 3.1 F2 induces proliferation of total splenocytes ................................................ 21 3.2 Identification of the splenocyte subpopulations activated by F2.................. 26 3.3 F2 stimulation promotes the differentiation of CD4 T lymphocytes towards a Th1 response ................................................................................................. 28 3.4 F2 stimulates B lymphocyte proliferation directly ....................................... 33 3.5 F2 stimulation increases the expression of activation surface marker on B lymphocytes .................................................................................................. 33 3.6 F2 induces IgM production in B lymphocytes ............................................. 37 3.7 F2 induces B lymphocytes to differentiate into plasma cells ....................... 37 3.8 F2 induces MAPK and NF-κB activation ..................................................... 41 3.9 F2 induces Syk pathway activation .............................................................. 49 Chapter 4 Discussion................................................................................................ 51 Chapter 5 Reference ................................................................................................ 55 LIST OF FIGURES Fig. 1 Schematic diagram of the MAPK signaling pathways. .................................. 8 Fig. 2 F2 induced significant proliferation of C57BL/6 mouse splenocyte in vitro.23 Fig. 3 Polymyxin B inhibited LPS activity, but not F2 activity in C57BL/6 mouse splenocyte..................................................................................................... 24 Fig. 4 F2-induced splenocyte proliferation was not significantly decreased after protease K treatment. ................................................................................. 25 Fig. 5 Analysis of the enlarged subpopulations of splenocytes by flow cytometry.27 Fig. 6 F2 could not stimulate CD4 T lymphocyte proliferation directly. ............... 30 Fig. 7 F2 stimulation promoted the differentiation of CD4 T lymphocytes towards a Th1 response in the splenocyte culture. ................................................. 31 Fig. 8 F2 stimulated IFN-γ production in the splenocyte culture. .......................... 32 Fig. 9 F2 stimulated B lymphocyte proliferation directly. ...................................... 34 Fig. 10 F2 stimulation increased the expression of activation surface markers (CD69 and CD86) on B lymphocytes. ....................................................... 35 Fig. 11 F2 induced IgM production in B lymphocytes. ........................................... 38 Fig. 12 F2 stimulation increased the expression of surface marker, CD138. ......... 39 Fig. 13 F2-stimulated IgM production was suppressed by the ERK inhibitor. ..... 43 Fig. 14 F2-stimulated IgM production was suppressed by the JNK inhibitor. ..... 44 Fig. 15 F2-stimulated IgM production was suppressed by the p38 inhibitor. ....... 45 Fig. 16 F2 - stimulated IgM production was suppressed the NF-κB inhibitor. ..... 46 Fig. 17 F2 stimulated ERK phosphorylation in B lymphocytes. ............................ 47 Fig. 18 F2 stimulated JNK phosphorylation in B lymphocytes. ............................. 48 Fig. 19 F2-stimulated IgM production was suppressed by the Syk inhibitor. ...... 50 LIST OF TABLES Table 1 PCR primer sequences for mRNA quantitation by qRT-PCR. ............... 15 Table 2 F2 stimulation increased the expression of activation surface markers . 36 Table 3 F2 stimulation increased the expression of surface marker, CD138. ...... 40 | |
| dc.language.iso | en | |
| dc.subject | B 淋巴球活化 | zh_TW |
| dc.subject | 台灣紫芝 | zh_TW |
| dc.subject | 多醣 | zh_TW |
| dc.subject | T 淋巴球分化 | zh_TW |
| dc.subject | Th 1 免疫反應 | zh_TW |
| dc.subject | B lymphocyte activation | en |
| dc.subject | Ganoderma formosanum | en |
| dc.subject | polysaccharides | en |
| dc.subject | T lymphocyte differentiation | en |
| dc.subject | Th1response | en |
| dc.title | 台灣紫芝多醣體對淋巴細胞免疫調節之研究 | zh_TW |
| dc.title | Immunomodulatory activity of Ganoderma formosanum
polysaccharides in lymphocytes | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林璧鳳,林國儀,繆希椿 | |
| dc.subject.keyword | 台灣紫芝,多醣,T 淋巴球分化,Th 1 免疫反應,B 淋巴球活化, | zh_TW |
| dc.subject.keyword | Ganoderma formosanum,polysaccharides,T lymphocyte differentiation,Th1response,B lymphocyte activation, | en |
| dc.relation.page | 61 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-07-23 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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