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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉扶東(Fu-Tong Liu) | |
| dc.contributor.author | Yu-Jung Chen | en |
| dc.contributor.author | 陳宥蓉 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:12:21Z | - |
| dc.date.copyright | 2014-10-09 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-08-15 | |
| dc.identifier.citation | References
1. Skeik, N. and F.I. Jabr, Influenza viruses and the evolution of avian influenza virus H5N1. Int J Infect Dis, 2008. 12(3): p. 233-8. 2. Suarez, D.L. and S. Schultz-Cherry, Immunology of avian influenza virus: a review. Dev Comp Immunol, 2000. 24(2–3): p. 269-283. 3. Samji, T., Influenza A: understanding the viral life cycle. Yale J Biol Med, 2009. 82(4): p. 153-9. 4. Nicholson, K.G., J.M. Wood, and M. Zambon, Influenza. Lancet, 2003. 362(9397): p. 1733-45. 5. Skehel, J.J. and D.C. Wiley, Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem, 2000. 69: p. 531-69. 6. Korteweg, C. and J. Gu, Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans. Am J Pathol, 2008. 172(5): p. 1155-1170. 7. Thanh, T.T., H.R. van Doorn, and M.D. de Jong, Human H5N1 influenza: current insight into pathogenesis. Int J Biochem Cell Biol, 2008. 40(12): p. 2671-4. 8. Hofmann, P., et al., Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response. J Leukoc Biol, 1997. 61(4): p. 408-14. 9. Kreijtz, J.H., R.A. Fouchier, and G.F. Rimmelzwaan, Immune responses to influenza virus infection. Virus Res, 2011. 162(1-2): p. 19-30. 10. Guillot, L., et al., Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J Biol Chem, 2005. 280(7): p. 5571-80. 11. Liu, P., et al., Retinoic acid-inducible gene I mediates early antiviral response and Toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells. J Virol, 2007. 81(3): p. 1401-11. 12. Lund, J.M., et al., Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci U S A, 2004. 101(15): p. 5598-603. 13. Allen, I.C., et al., The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity, 2009. 30(4): p. 556-65. 14. Thomas, P.G., et al., The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity, 2009. 30(4): p. 566-75. 15. Ada, G.L. and P.D. Jones, The immune response to influenza infection. Curr Top Microbiol Immunol, 1986. 128: p. 1-54. 16. Herold, S., et al., Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: impact of chemokines and adhesion molecules. J Immunol, 2006. 177(3): p. 1817-24. 17. Tumpey, T.M., et al., Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J Virol, 2005. 79(23): p. 14933-44. 18. McGill, J., J.W. Heusel, and K.L. Legge, Innate immune control and regulation of influenza virus infections. J Leukoc Biol, 2009. 86(4): p. 803-12. 19. GeurtsvanKessel, C.H., et al., Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus-infected mice. J Exp Med, 2009. 206(11): p. 2339-49. 20. GeurtsvanKessel, C.H., et al., Both conventional and interferon killer dendritic cells have antigen-presenting capacity during influenza virus infection. PLoS One, 2009. 4(9): p. e7187. 21. Doherty, P.C. and A. Kelso, Toward a broadly protective influenza vaccine. J Clin Invest, 2008. 118(10): p. 3273-5. 22. Lamb, J.R., et al., In vitro influenza virus-specific antibody production in man: antigen-specific and HLA-restricted induction of helper activity mediated by cloned human T lymphocytes. J Immunol, 1982. 129(4): p. 1465-70. 23. Gerhard, W., The role of the antibody response in influenza virus infection. Curr Top Microbiol Immunol, 2001. 260: p. 171-90. 24. Mozdzanowska, K., et al., Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies specific for the transmembrane proteins matrix 2 and neuraminidase reduces the pulmonary virus titer but fails to clear the infection. Virology, 1999. 254(1): p. 138-46. 25. Peiris, J.S., et al., Innate immune responses to influenza A H5N1: friend or foe? Trends Immunol, 2009. 30(12): p. 574-84. 26. Beigel, J.H., et al., Avian influenza A (H5N1) infection in humans. N Engl J Med, 2005. 353(13): p. 1374-85. 27. de Jong, M.D., et al., Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med, 2006. 12(10): p. 1203-7. 28. Shinya, K., et al., Avian flu: influenza virus receptors in the human airway. Nature, 2006. 440(7083): p. 435-6. 29. de Jong, M.D., et al., Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med, 2005. 352(7): p. 686-91. 30. Damjanovic, D., et al., Immunopathology in influenza virus infection: uncoupling the friend from foe. Clin Immunol, 2012. 144(1): p. 57-69. 31. Snelgrove, R.J., et al., A critical function for CD200 in lung immune homeostasis and the severity of influenza infection. Nat Immunol, 2008. 9(9): p. 1074-83. 32. Lin, K.L., et al., CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J Immunol, 2008. 180(4): p. 2562-72. 33. La Gruta, N.L., et al., A question of self-preservation: immunopathology in influenza virus infection. Immunol Cell Biol, 2007. 85(2): p. 85-92. 34. Shaw, M.W., N.H. Arden, and H.F. Maassab, New aspects of influenza viruses. Clin Microbiol Rev, 1992. 5(1): p. 74-92. 35. Narasaraju, T., et al., Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol, 2011. 179(1): p. 199-210. 36. Aldridge, J.R., Jr., et al., TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci U S A, 2009. 106(13): p. 5306-11. 37. Xu, L., et al., Cutting edge: pulmonary immunopathology mediated by antigen-specific expression of TNF-alpha by antiviral CD8+ T cells. J Immunol, 2004. 173(2): p. 721-5. 38. Barondes, S.H., et al., Galectins. Structure and function of a large family of animal lectins. J Biol Chem, 1994. 269(33): p. 20807-10. 39. Hirabayashi, J. and K. Kasai, The family of metazoan metal-independent beta-galactoside-binding lectins: structure, function and molecular evolution. Glycobiology, 1993. 3(4): p. 297-304. 40. Krzeslak, A. and A. Lipinska, Galectin-3 as a multifunctional protein. Cell Mol Biol Lett, 2004. 9(2): p. 305-28. 41. Ahmad, N., et al., Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. J Biol Chem, 2004. 279(12): p. 10841-7. 42. Liu, F.T. and G.A. Rabinovich, Galectins: regulators of acute and chronic inflammation. Ann N Y Acad Sci, 2010. 1183: p. 158-82. 43. Dumic, J., S. Dabelic, and M. Flogel, Galectin-3: an open-ended story. Biochim Biophys Acta, 2006. 1760(4): p. 616-35. 44. Liu, F.T., R.J. Patterson, and J.L. Wang, Intracellular functions of galectins. Biochim Biophys Acta, 2002. 1572(2-3): p. 263-73. 45. Chen, H.Y., F.T. Liu, and R.Y. Yang, Roles of galectin-3 in immune responses. Arch Immunol Ther Exp (Warsz), 2005. 53(6): p. 497-504. 46. Yang, R.Y., D.K. Hsu, and F.T. Liu, Expression of galectin-3 modulates T-cell growth and apoptosis. Proc Natl Acad Sci U S A, 1996. 93(13): p. 6737-42. 47. Kim, H.R., et al., Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. Cancer Res, 1999. 59(16): p. 4148-54. 48. Lin, H.M., et al., Galectin-3 mediates genistein-induced G(2)/M arrest and inhibits apoptosis. Carcinogenesis, 2000. 21(11): p. 1941-5. 49. Dagher, S.F., J.L. Wang, and R.J. Patterson, Identification of galectin-3 as a factor in pre-mRNA splicing. Proc Natl Acad Sci U S A, 1995. 92(4): p. 1213-7. 50. Fukushi, J., I.T. Makagiansar, and W.B. Stallcup, NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin. Mol Biol Cell, 2004. 15(8): p. 3580-90. 51. Demetriou, M., et al., Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature, 2001. 409(6821): p. 733-9. 52. Liu, F.T. and G.A. Rabinovich, Galectins as modulators of tumour progression. Nat Rev Cancer, 2005. 5(1): p. 29-41. 53. Saegusa, J., et al., Galectin-3 Is Critical for the Development of the Allergic Inflammatory Response in a Mouse Model of Atopic Dermatitis. Am J Pathol, 2009. 174(3): p. 922-931. 54. Vasta, G.R., Roles of galectins in infection. Nat Rev Microbiol, 2009. 7(6): p. 424-38. 55. Sano, H., et al., Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J Immunol, 2000. 165(4): p. 2156-64. 56. Kuwabara, I. and F.T. Liu, Galectin-3 promotes adhesion of human neutrophils to laminin. J Immunol, 1996. 156(10): p. 3939-44. 57. Sato, S., et al., Role of galectin-3 as an adhesion molecule for neutrophil extravasation during streptococcal pneumonia. J Immunol, 2002. 168(4): p. 1813-22. 58. Sano, H., et al., Critical role of galectin-3 in phagocytosis by macrophages. J Clin Invest, 2003. 112(3): p. 389-97. 59. Norling, L.V., M. Perretti, and D. Cooper, Endogenous galectins and the control of the host inflammatory response. J Endocrinol, 2009. 201(2): p. 169-84. 60. Hsu, D.K., et al., Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses. Am J Pathol, 2000. 156(3): p. 1073-83. 61. Colnot, C., et al., Maintenance of granulocyte numbers during acute peritonitis is defective in galectin-3-null mutant mice. Immunology, 1998. 94(3): p. 290-6. 62. Nieminen, J., et al., Role of galectin-3 in leukocyte recruitment in a murine model of lung infection by Streptococcus pneumoniae. J Immunol, 2008. 180(4): p. 2466-73. 63. Fukumori, T., et al., CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis. Cancer Res, 2003. 63(23): p. 8302-11. 64. Mey, A., et al., The animal lectin galectin-3 interacts with bacterial lipopolysaccharides via two independent sites. J Immunol, 1996. 156(4): p. 1572-7. 65. Moody, T.N., J. Ochieng, and F. Villalta, Novel mechanism that Trypanosoma cruzi uses to adhere to the extracellular matrix mediated by human galectin-3. FEBS Lett, 2000. 470(3): p. 305-8. 66. Sato, S. and J. Nieminen, Seeing strangers or announcing 'danger': galectin-3 in two models of innate immunity. Glycoconj J, 2004. 19(7-9): p. 583-91. 67. Kim, H., et al., Expression and immunohistochemical localization of galectin-3 in various mouse tissues. Cell Biol Int, 2007. 31(7): p. 655-62. 68. Pilette, C., et al., Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD. Eur Respir J, 2007. 29(5): p. 914-22. 69. Zuberi, R.I., et al., Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma. Am J Pathol, 2004. 165(6): p. 2045-53. 70. Yang, M.L., et al., Galectin-1 binds to influenza virus and ameliorates influenza virus pathogenesis. J Virol, 2011. 85(19): p. 10010-20. 71. Hattori, T.A., et al., Inhibition of influenza A virus infection by Galectin-9. JPN J Vet Res, 2013. 61(1&2): p. 5-18. 72. Sharma, S., et al., T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses. Proc Natl Acad Sci U S A, 2011. 108(47): p. 19001-6. 73. Chan, M.C., et al., Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir Res, 2005. 6: p. 135. 74. Wood, J.M. and J.S. Robertson, From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza. Nat Rev Microbiol, 2004. 2(10): p. 842-7. 75. Jungblut, M., et al., Standardized preparation of single-cell suspensions from mouse lung tissue using the gentleMACS Dissociator. J Vis Exp, 2009(29). 76. Vareille, M., et al., The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev, 2011. 24(1): p. 210-29. 77. Williams, A.E. and R.C. Chambers, The mercurial nature of neutrophils: still an enigma in ARDS? Am J Physiol Lung Cell Mol Physiol, 2014. 306(3): p. L217-30. 78. van de Veerdonk, F.L. and M.G. Netea, New Insights in the Immunobiology of IL-1 Family Members. Front Immunol, 2013. 4: p. 167. 79. Schmitz, N., et al., Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection. J Virol, 2005. 79(10): p. 6441-8. 80. Schoenborn, J.R. and C.B. Wilson, Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol, 2007. 96: p. 41-101. 81. Weiss, I.D., et al., IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner. J Interferon Cytokine Res, 2010. 30(6): p. 439-49. 82. Price, G.E., A. Gaszewska-Mastarlarz, and D. Moskophidis, The role of alpha/beta and gamma interferons in development of immunity to influenza A virus in mice. J Virol, 2000. 74(9): p. 3996-4003. 83. Chen, H.Y., et al., Galectin-3 negatively regulates TCR-mediated CD4+ T-cell activation at the immunological synapse. Proc Natl Acad Sci U S A, 2009. 106(34): p. 14496-501. 84. Gessani, S. and F. Belardelli, IFN-gamma expression in macrophages and its possible biological significance. Cytokine Growth Factor Rev, 1998. 9(2): p. 117-23. 85. Ferraz, L.C., et al., Lack of galectin-3 alters the balance of innate immune cytokines and confers resistance to Rhodococcus equi infection. Eur J Immunol, 2008. 38(10): p. 2762-75. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18570 | - |
| dc.description.abstract | A型流行性感冒病毒H5N1是一株高致病性的禽流感病毒，感染人類會引發肺炎、甚至是急性呼吸窘迫症候群，病毒所引起的細胞激素失調與促發炎細胞激素的過度產生是人類H5N1感染的致病原因之一。半乳糖凝素-3屬於動物凝集素，其共有的醣類辨識區域(carbohydrate recognition domain, CRD)可辨識具有β型半乳糖修飾的醣類。半乳糖凝素-3廣泛存在，特別是免疫與上皮細胞中，也存在於流行性感冒病毒主要的感染區域—呼吸道中。許多文獻指出半乳糖凝素-3可以調節免疫功能並且具有促進發炎的活性，也發現半乳糖凝素-3的表現與肺部損傷有關。近來研究指出外加半乳糖凝素-1和半乳糖凝素-9可抑制A型流感病毒感染，另有研究顯示內生性的半乳糖凝素-9會抑制A型流感病毒專一性的CD8 T細胞與體液免疫反應。然而，目前仍不清楚內生性的半乳糖凝素-3對於流感病毒感染的影響。
我的研究主題是探討內生性半乳糖凝素-3在H5N1流感病毒感染中的角色，特別著重於H5N1流感病毒所引起的宿主免疫反應。實驗結果顯示，在感染H5N1病毒後，半乳糖凝素-3基因剔除鼠的存活率較野生型小鼠高，表示半乳糖凝素-3基因剔除鼠較不受H5N1流感病毒感染的影響，然而，兩組小鼠中的病毒量相當。藉由蘇木素-伊紅組織染色（H&E Stain）發現半乳糖凝素-3基因剔除鼠在感染後的肺部發炎與細胞浸潤情形比較輕緩，由免疫組織染色的結果觀察到小鼠肺部中半乳糖凝素-3的表現量在感染H5N1病毒後上升，且主要由浸潤細胞表現。此外，利用流式細胞術分析浸潤細胞的組成，結果顯示受感染的半乳糖凝素-3基因剔除鼠肺部中，嗜中性白血球與巨噬細胞的比例明顯較野生型小鼠低。另外比較兩組小鼠感染後肺部中的細胞激素(cytokines)，發現半乳糖凝素-3基因剔除鼠中的IL-1β濃度較低、IFN-γ濃度則較高。我們進一步利用細胞實驗探討半乳糖凝素-3對於細胞激素產生的影響，結果指出相較於控制組，取自半乳糖凝素-3基因剔除鼠的bone marrow-derived macrophages在H5N1病毒感染下釋放出較少量的促發炎細胞激素(proinflammatory cytokines) 與趨化激素(chemokines)，而半乳糖凝素-3基因敲落的人類肺部上皮細胞株A549也在H5N1病毒感染下釋放出較少量的促發炎細胞激素IL-6、IFN-β與趨化激素MCP-1以及IL-8。 總結我們在探討半乳糖凝素-3於H5N1病毒感染引發之宿主免疫反應中的角色所得之實驗結果，我們推論半乳糖凝素-3可能藉由促進特定促發炎細胞激素或趨化激素的產生，以及免疫細胞的趨化，進而強化H5N1病毒的病理作用，導致嚴重肺部發炎。而半乳糖凝素-3是藉由何種機制調控細胞激素或趨化激素的產生與免疫細胞的趨化則需要更進一步的研究。此研究幫助我們了解半乳糖凝素-3在H5N1病毒致病過程中的角色，並且暗示半乳糖凝素-3也許可以發展為H5N1病毒感染引發之嚴重肺部發炎的治療標的，以期減緩過度的免疫反應。 | zh_TW |
| dc.description.abstract | H5N1 is a highly pathogenic strain of avian influenza virus. Human H5N1 influenza infection causes pneumonia and leads to acute respiratory distress syndrome. Virus-induced cytokine dysregulation, which is characterized by excessive production of pro-inflammatory cytokines, contributes to the pathogenesis of human H5N1 disease. Galectin-3 belongs to the galectin family, which are animal lectins recognizing β-galactoside-containing glycoconjugates by the carbohydrate recognition domains. Galectin-3 is widely distributed, particularly in immune and epithelial cells, and is also found in human airways, the primary infection site of influenza virus. Galectin-3 has been reported to regulate various immune functions and shows proinflammatory activity. Studies have indicated that galectin-3 is up-regulated in lung injury. Recently, exogenously added galectin-1 and -9 were reported to inhibit influenza A virus infection, whereas another study showed the inhibitory effect of endogenous galectin-9 on influenza A virus-specific CD8 T-cell and humoral responses. However, the function of endogenous galectin-3 in H5N1 influenza A virus infection is unclear.
This project is aimed to investigate the role of endogenous galectin-3 in H5N1 influenza A virus infection, especially in H5N1-induced host immune responses. Our results showed that galectin-3 knockout (Gal-3KO) mice were less susceptible to H5N1 virus infection and had higher survival rates compared to wild-type (WT) mice. However, the viral loads were comparable between WT and Gal-3KO mice. H&E staining data indicated that Gal-3KO mice exhibited lower degrees of inflammation and neutrophil infiltrations in the lungs. By using immunohistochemistry (IHC) staining, we observed that galectin-3 was up-regulated in the lungs after H5N1 infection, and the increased galectin-3 was mainly expressed by the infiltrating cells. Besides, results from flow cytometry showed that lower frequency of macrophages and neutrophils were recruited to the lungs of infected Gal-3KO mice. In addition, lower and higher levels of IL-1β and IFN-γ were detected in the lungs of infected Gal-3KO mice, respectively. We also found that lower proinflammatory cytokines and chemokine were produced from bone marrow-derived macrophages of Gal-3KO mice compared to the WT mice during H5N1 infection. Moreover, knocking down galetcin-3 in A549 human lung epithelial cells reduced the production of proinflammatory cytokine IL-6, IFN-β and chemokines, such as MCP-1 and IL-8 in response to H5N1. Combined, our results suggest that galectin-3 may enhance the pathological effects of H5N1 virus infection by promoting the production of certain proinflammatory cytokines or chemokines, and the recruitment of immune cells, which consequently leads to more severe inflammation. Further studies are required to elucidate how endogenous galectin-3 regulates cytokine production and immune cell recruitment during H5N1 infection. Continued studies will help us understand the role of galectin-3 in H5N1 pathogenesis, and evaluate the possibility of galectin-3 as a therapeutic target for H5N1-induced severe lung inflammation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:12:21Z (GMT). No. of bitstreams: 1 ntu-103-R01449003-1.pdf: 3799298 bytes, checksum: 4b56b3b67d5386868cd40802379ac287 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | Content
誌謝 I 摘要 II Abstract IV Introduction 1 1. Highly pathogenic avian influenza virus H5N1 1 1.1 Characterization of avian influenza virus H5N1 1 1.2 Host immune responses to influenza A virus 2 1.3 Pathogenesis of H5N1 in humans 4 2. Galectin-3 5 2.1 Galectin family 5 2.2 The general functions of galectin-3 6 2.3 The role of galectin-3 in immune responses 7 Experimental design 8 Materials and methods 10 1. Cell lines 10 2. H5N1 virus propagation 10 3. Hemagglutination assay 11 4. Mouse and Animal studies 11 5. RNA extraction and Reverse Transcription-PCR 11 6. Quantification of H5N1 virus by Real-time PCR 12 7. Galectin expression at the mRNA level 12 8. Histochemical analysis 13 9. ELISA 14 10. Mouse lung single cell suspension 14 11. Flow cytometry and quantification of immune cells in lung 15 12. Bio-plex assay 16 13. Preparation of mouse bone marrow-derived macrophages (BMDM) 16 14. Generation of galectin-3 knockdown A549 cells by shRNA-expressing lentiviral infection 17 15. Infection of cell culture with H5N1 17 16. Western blot 18 17. Statistic analysis 18 Results 20 1. The effect of galectin-3 on H5N1 infection in vivo 20 1.1 The expression level of galectin-3 during H5N1 infection 20 1.2 The effect of galectin-3 on body weight and survival of mice inoculated with H5N1 20 1.3 The effect of galectin-3 on viral loads in the lungs of mice infected with H5N1 21 2. The effect of galectin-3 on H5N1-induced immune responses 21 2.1 The effect of galectin-3 on inflammation severity induced by H5N1 21 2.2 The sources of the up-regulated galectin-3 in lung during H5N1 infection 22 2.3 The effect of galectin-3 on immune cells recruitment upon H5N1 infection 22 2.4 Cytokine expression profile in Wild-type and galectin-3 knockout mice during H5N1 infection 23 3. The effect of galectin-3 on cytokines production in response to H5N1 in vitro 24 3.1 The effect of galectin-3 on cytokine production in H5N1-infected mouse bone marrow-derived macrophages 24 3.2 The effect of galectin-3 on cytokine secretion in H5N1-infected human lung epithelial cell line A549 24 Discussion and Future work 27 References 34 Figure content Figure 1. The viral loads and galectin-3 expression are up-regulated in lungs during H5N1 infection 41 Figure 2. Gal-3 KO mice exhibit higher survival and lower weight loss during H5N1 infection compared to WT mice 42 Figure 3. The viral copies in lungs of Gal-3 KO mice are comparable to those in WT mice 43 Figure 4. Gal-3KO mice exhibit reduced lung inflammation and neutrophil infiltration compared to WT mice during H5N1 infection 44 Figure 5. The increased level of galectin-3 in lung after H5N1 infection is mostly contributed by the infiltrating cell 45 Figure 6. Lower percentages of neutrophils and macrophages, but not dendritic cells, NK cells, CD4 T cells and CD8 T cells infiltrate into the lungs of Gal-3KO mice upon H5N1 infection, compared to WT mice 46 Figure 7. The cytokine expression profile in lung homogenates 47 Figure 8. The Gal-3 KO mice express lower level of IL-1β but higher level of IFN-γ in BAL fluid relative to WT mice 48 Figure 9. Gal-3 KO BMDM secrete lower levels of proinflammatory cytokines IL-1β, TNF-α, IL-6 and chemokine MCP-1 than WT BMDM in response to H5N1 infection 49 Figure 10. Galectin-3-knockdown A549 cells secrete lower levels of IFN-β, chemokines MCP-1 and IL-8 than control A549 cells in response to H5N1 infection 50 Appendix content Appendix 1 51 Appendix 2 52 | |
| dc.language.iso | en | |
| dc.title | 半乳糖凝集素-3在流行性感冒病毒引發之宿主免疫反應中所扮演的角色 | zh_TW |
| dc.title | The Role of Galectin-3 in Influenza Virus-Induced Host Immune Responses | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 江伯倫(Bor-Luen Chiang),張雅貞(Ya-Jen Chang) | |
| dc.subject.keyword | 半乳糖凝集素-3,A型流行性感冒病毒,H5N1,免疫反應,發炎,細胞激素, | zh_TW |
| dc.subject.keyword | Galectin-3,influenza A virus,H5N1,immune responses,inflammation,cytokines, | en |
| dc.relation.page | 54 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2014-08-15 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-103-1.pdf 未授權公開取用 | 3.71 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。