臺灣博碩士論文加值系統

氣喘是一種慢性呼吸道發炎性疾病，在全世界無論是在已發展或發展中的國家，都是非常普遍的疾病。造成氣喘發炎反應的原因，主要是因為Ｔ輔助型細胞的發育偏向Th2細胞型免疫反應；其產生的細胞激素以IL-4、IL-5和IL-13為主。氣喘發炎反應就是由在這些細胞激素與體內過敏原專一性IgE抗體的主導下，啟開一連串的連鎖反應所造成的。其主要臨床症狀包括了氣管收縮、氣管過度反應和氣管發炎反應。已經有強烈的證據證明了，直接給予Th1細胞激素或是利用刺激的方式增加Th1細胞激素的產生，例如給予IFN-α，IFN-γ，IL-12 或CpG-motif oligodexynucleotide皆可降低Th2呼吸道的發炎反應，進而達到治療氣喘動物模式的目的。而樹突細胞是一個專業的抗原呈獻細胞，具有可以調控T細胞分化走向的能力。忍冬葉桑寄生（T. lonicerifolius var. lonicerifolius）屬於桑寄生科（Loranthaceae），鈍果桑寄生屬（Taxillus），是台灣特有種的桑寄生植物。在本實驗中，我們取用由長庚大學天然藥物所呂彥禮助理教授所提供的忍冬葉桑寄生萃取物，研究其對於樹突細胞的影響。實驗發現，給予忍冬葉桑寄生萃取物可增加樹突細胞IL-12p40，IL-12p70和IL-10的表現。同時也可增加樹突細胞CD80、CD86、MHCI和MHCII等細胞表面分子的表現，並抑制樹突細胞的吞噬能力，刺激樹突細胞的成熟。進一步，利用anti-TLR-4抗體做中和反應的實驗，則發現IL-12p40的產生會受到抑制。因此認為，忍冬葉桑寄生萃取物可透過TLR-4的訊息傳遞以刺激樹突細胞的反應。另外，利用受刺激修飾後的樹突細胞與T細胞共同培養，發現可增加Ｔ細胞增生能力以及分泌IFN-γ的能力。總結於in vitro的結果，忍冬葉桑寄生萃取物具有調節免疫反應的能力。進一步利用I.P.注射忍冬葉桑寄生萃取物與OVA抗原混和液，建立小鼠動物模式，以探討忍冬葉桑寄生萃取物對OVA專一性細胞免疫反應走向的影響。結果發現，給予忍冬葉桑寄生萃取物作為佐劑的組別，小鼠血清中的OVA抗原專一性IgG2a有顯著性的增加；而OVA抗原專一性IgＥ有顯著性的抑制。雖然在脾臟細胞培養實驗中，IFN-γ並無顯著性的增加，但是IL-4和IL-5細胞激素皆有顯著性的降低。這顯示以忍冬葉桑寄生萃取物作為佐劑，確實具有刺激BALB/c小鼠抗原專一性免疫反應傾向Th1細胞免疫反應發展。由於這些發現，我們認為忍冬葉桑寄生萃取物是一個具有可以治療氣喘動物模式的化合物。在未來，我們將進一步利用忍冬葉桑寄生萃取物對氣喘小鼠做治療的研究。

Allergic asthma is one of the most important Th2 lymphocyte-mediated chronic inflammatory airway disease worldwide, both in the developing and developed countries. In the patients of allergic asthma, it is well characterized by skewed polarization of helper T cell development toward type 2 T helper cell with increased production of interleukin 4 (IL-4) and IL-5. Asthma is characterized by airway eosinophils inflammation, mucus hypersecretion, bronchial hyperreactivity, the presence of high levels of allergen-specific IgE. There is strong evidence for the therapeutic effect of type 1 T helper-related cytokines or reagents, such as IFN-α, IFN-γ, IL-12 or CpG-motif oligodexynucleotide on airway inflammation. Dendritic cell are the most potent antigen presenting cells for priming the naïve T helper cells. Taxillus lonicerifolius var. lonicerifolius is one species of Loranthaceae in Taiwan. One pure compound (1400041), kindly providing by Pro. Leu,. isolated from the fresh T. lonicerifolius var. lonicerifolius was used in this study. In this study, we found stimulating BM-DC with 30μg/ml 1400041 could enhance production of IL-12 p40, IL-12 p70 and IL-10, as well as enhance cell surface expression of CD80 (B7.1), CD86 (B7.2), MHCI and MHCII molecule. In addition, the capacity for endocytosis was suppressed in BM-DC treated with 1400041. And, neutralization with antibody against Toll-like receptor（TLR）-4 inhibited the 1400041-induced production of IL-12 p40, suggest a crucial role for TLR-4 in signaling DC upon incubation with 1400041. In addition, treatment of BM-DC with 1400041 resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of IFN-γ. Taken together, our in vitro data demonstrated that this 1400041 can effectively promote the activation and maturation of DC, suggesting that 1400041 may possess a potential in regulating immune responses. To test the effect of 1400041 in vivo, we further examined the effects of this compound on antigen-specific antibody and cytokine production. Immunization with ovalbumin (OVA) / 1400041 showed that the anti-OVA IgG2a levels were significantly increased and the anti-OVA IgE levels were significantly decreased compared with that of OVA-alone group. While 1400041 had no significantly effect on the anti-OVA IgG1 levels and induced the secretion of IFN-g, it inhibited the secretion of IL-4 and IL-5. The findings demonstrate that 1400041 could be used as adjuvant to induce Th1 immunity in BALB/c mice. In the future, we aim to study the therapeutic effect and immune modulatory mechanism of 1400041 in murine model of asthma. We expect this compound might be used as novel therapeutic reagent for asthma treatment.

封面
論文口試委員審定書
致謝
中文摘要…………………………………………………………………………… i
英文摘要…………………………………………………………………………… iii
縮寫對照表………………………………………………………………………… v
目錄………………………………………………………………………………… vii
第一章 背景及文獻資料回顧……………………………………………………… 1
1.1. 氣喘疾病之介紹………………………………………………………… 2
1.1.1. T細胞在氣喘中所扮演的角色…………………………………… 3
1.1.2. 與氣喘相關的細胞激素及趨化因子…………………………… 3
1.1.3. 樹突細胞在氣喘中所扮演的角色……………………………… 4
1.1.4. IgE抗體及肥胖細胞的在氣喘中所扮演的角色………………… 6
1.1.5. 氣喘動物模式的建立…………………………………………… 6
1.1.6. 治療氣喘的方式………………………………………………… 7
1.1.6.1. 利用給予IL-12細胞激素以增強Th1細胞免疫反應………… 8
1.2. 忍冬葉桑寄生之介紹…………………………………………………… 10
第二章 論文研究目的……………………………………………………………… 12
第三章 探討忍冬葉桑寄生萃取物對樹突細胞的影響，及是否可藉由刺激樹
突細胞進而調控CD4+ T 細胞的分化……………………………………………… 15
3.1實驗目的及原理…………………………………………………………… 16
3.2 實驗材料及方法…………………………………………………………… 17
3.3 實驗結果…………………………………………………………………… 22
3.3.1 培養骨髓衍生樹突細胞…………………………………………… 22
3.3.2. 忍冬葉桑寄生萃取物對樹突細胞細胞激素分泌能力的影響…… 22
3.3.3. 忍冬葉桑寄生萃取物對樹突細胞對細胞表面分子的影響……… 23
3.3.4. 忍冬葉桑寄生萃取物對樹突細胞吞噬能力的影響……………… 23
3.3.5. 忍冬葉桑寄生萃取物處理過後的樹突細胞，對於CD4+ T
細胞分化走向之影響…………………………………………… 23
第四章 探討忍冬葉桑寄生萃取物在小鼠動物模式中的影響…………………… 25
4..1. 探討忍冬葉桑寄生萃取物在小鼠動物模式中誘導OVA專一性細胞反
應走向Th1細胞反應之能力……………………………………………… 26
4.1.1. 實驗目的及原理…………………………………………………… 27
4.1.2. 實驗材料及方法…………………………………………………… 30
4.1.3. 實驗結果…………………………………………………………… 30
4.1.3.1. 給予不同濃度忍冬葉桑寄生萃取物作為佐劑，對於
血清中OVA專一性IgG2a、IgG1、IgE表現的影響……… 30
4.1.3.2. 給予忍冬葉桑寄生萃取物作為佐劑可增加脾臟細胞
增生反應……………………………………………………… 30
4.1.3.3. 給予不同濃度忍冬葉桑寄生萃取物作為佐劑，對於
脾臟細胞之細胞激素分泌的影響…………………………… 30
4.2. 探討忍冬葉桑寄生萃取物在OVA專一性氣喘動物模式中的治療效果 32
第五章 結論……………………………………………………………………… 34
5.1. 探討忍冬葉桑寄生萃取物對樹突細胞的影響，及是否可藉由刺激
樹突細胞進而調控CD4+ T 細胞的分化……………………………… 35
5.2 探討忍冬葉桑寄生萃取物在小鼠動物模式中誘導OVA專一性細胞
反應走向Th1細胞反應之能力………………………………………… 37
5.3 探討忍冬葉桑寄生萃取物在OVA專一性氣喘動物模式中的治療效果 38
圖…………………………………………………………………………………… 40
參考文獻…………………………………………………………………………… 55
附錄………………………………………………………………………………… 64

Adkinson, N.F., Jr., Eggleston, P.A., Eney, D., Goldstein, E.O., Schuberth, K.C., Bacon, J.R., et al (1997) A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med. 336: 324-331.
Agrawal, S., Agrawal, A., Doughty, B., Gerwitz, A., Blenis, J., Van Dyke, T. and Pulendran, B. (2003) Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol. 171: 4984-4989.
Banchereau, J. and Steinman, R.M. (1998) Dendritic cells and the control of immunity. Nature. 392: 245-252.
Bermudez-Humaran, L.G., Langella, P., Cortes-Perez, N.G., Gruss, A., Tamez-Guerra, R.S., Oliveira, S.C., et al (2003) Intranasal immunization with recombinant Lactococcus lactis secreting murine interleukin-12 enhances antigen-specific Th1 cytokine production. Infect Immun. 71: 1887-1896.
Bruselle, G.G., Kips, J.C., Peleman, R.A., Joos, G.F., Devos, R.R., Tavernier, J.H. and Pauwels, R.A. (1997) Role of IFN-gamma in the inhibition of the allergic airway inflammation caused by IL-12. Am J Respir Cell Mol Biol. 17: 767-771.
Busse, W.W. and Lemanske, R.F., Jr. (2001) Asthma. N Engl J Med. 344: 350-362.
Campbell, D., DeKruyff, R.H. and Umetsu, D.T. (2000) Allergen immunotherapy: novel approaches in the management of allergic diseases and asthma. Clin Immunol. 97: 193-202.
Cella, M., Sallusto, F. and Lanzavecchia, A. (1997a) Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol. 9: 10-16.
Cella, M., Engering, A., Pinet, V., Pieters, J. and Lanzavecchia, A. (1997b) Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature. 388: 782-787.
Cella, M., Salio, M., Sakakibara, Y., Langen, H., Julkunen, I. and Lanzavecchia, A. (1999) Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J Exp Med. 189: 821-829.
Chiang, D.J., Ye, Y.L., Chen, W.L., Lee, Y.L., Hsu, N.Y. and Chiang, B.L. (2003) Ribavirin or CpG DNA sequence-modulated dendritic cells decrease the IgE level and airway inflammation. Am J Respir Crit Care Med. 168: 575-580.
Corrigan, C.J., Haczku, A., Gemou-Engesaeth, V., Doi, S., Kikuchi, Y., Takatsu, K., et al (1993) CD4 T-lymphocyte activation in asthma is accompanied by increased serum concentrations of interleukin-5. Effect of glucocorticoid therapy. Am Rev Respir Dis. 147: 540-547.
Corry, D.B. (1999) IL-13 in allergy: home at last. Curr Opin Immunol. 11: 610-614.
de Jong, E.C., Smits, H.H. and Kapsenberg, M.L. (2005) Dendritic cell-mediated T cell polarization. Springer Semin Immunopathol. 26: 289-307.
DeKruyff, R.H., Fang, Y., Wolf, S.F. and Umetsu, D.T. (1995) IL-12 inhibits IL-4 synthesis in keyhole limpet hemocyanin-primed CD4+ T cells through an effect on antigen-presenting cells. J Immunol. 154: 2578-2587.
Dent, L.A., Strath, M., Mellor, A.L. and Sanderson, C.J. (1990) Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med. 172: 1425-1431.
Dow, S.W., Schwarze, J., Heath, T.D., Potter, T.A. and Gelfand, E.W. (1999) Systemic and local interferon gamma gene delivery to the lungs for treatment of allergen-induced airway hyperresponsiveness in mice. Hum Gene Ther. 10: 1905-1914.
Foster, P.S., Hogan, S.P., Ramsay, A.J., Matthaei, K.I. and Young, I.G. (1996) Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 183: 195-201.
Gavett, S.H., O''Hearn, D.J., Li, X., Huang, S.K., Finkelman, F.D. and Wills-Karp, M. (1995) Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation, and Th2 cytokine expression in mice. J Exp Med. 182: 1527-1536.
Geha, R.S., Jabara, H.H. and Brodeur, S.R. (2003) The regulation of immunoglobulin E class-switch recombination. Nat Rev Immunol. 3: 721-732.
Gemou-Engesaeth, V., Fagerhol, M.K., Toda, M., Hamid, Q., Halvorsen, S., Groegaard, J.B. and Corrigan, C.J. (2002) Expression of activation markers and cytokine mRNA by peripheral blood CD4 and CD8 T cells in atopic and nonatopic childhood asthma: effect of inhaled glucocorticoid therapy. Pediatrics. 109: E24.
Grunewald, S.M., Werthmann, A., Schnarr, B., Klein, C.E., Brocker, E.B., Mohrs, M., et al (1998) An antagonistic IL-4 mutant prevents type I allergy in the mouse: inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo. J Immunol. 160: 4004-4009.
Hamid, Q.A. and Minshall, E.M. (2000) Molecular pathology of allergic disease: I: lower airway disease. J Allergy Clin Immunol. 105: 20-36.
Hartmann, G., Weiner, G.J. and Krieg, A.M. (1999) CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc Natl Acad Sci U S A. 96: 9305-9310.
Hasbold, J., Lyons, A.B., Kehry, M.R. and Hodgkin, P.D. (1998) Cell division number regulates IgG1 and IgE switching of B cells following stimulation by CD40 ligand and IL-4. Eur J Immunol. 28: 1040-1051.
Hendrzak, J.A. and Brunda, M.J. (1995) Interleukin-12. Biologic activity, therapeutic utility, and role in disease. Lab Invest. 72: 619-637.
Herz, U., Braun, A., Ruckert, R. and Renz, H. (1998) Various immunological phenotypes are associated with increased airway responsiveness. Clin Exp Allergy. 28: 625-634.
Huang, J.L. (2005) Asthma severity and genetics in Taiwan. J Microbiol Immunol Infect. 38: 158-163.
Keane-Myers, A., Wysocka, M., Trinchieri, G. and Wills-Karp, M. (1998) Resistance to antigen-induced airway hyperresponsiveness requires endogenous production of IL-12. J Immunol. 161: 919-926.
Kiniwa, M., Gately, M., Gubler, U., Chizzonite, R., Fargeas, C. and Delespesse, G. (1992) Recombinant interleukin-12 suppresses the synthesis of immunoglobulin E by interleukin-4 stimulated human lymphocytes. J Clin Invest. 90: 262-266.
Kurup, V.P., Murali, P.S., Guo, J., Choi, H., Banerjee, B., Fink, J.N. and Coffman, R.L. (1997) Anti-interleukin (IL)-4 and -IL-5 antibodies downregulate IgE and eosinophilia in mice exposed to Aspergillus antigens. Allergy. 52: 1215-1221.
Lambrecht, B.N., Salomon, B., Klatzmann, D. and Pauwels, R.A. (1998) Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol. 160: 4090-4097.
Lambrecht, B.N., De Veerman, M., Coyle, A.J., Gutierrez-Ramos, J.C., Thielemans, K. and Pauwels, R.A. (2000) Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest. 106: 551-559.
Lee, YL, Fu, CL. and Chiang, BL. (1999a) Administration of interleukin-12 exerts a therapeutic instead of a long-term preventive effect on mite Der p I allergen-induced animal model of airway inflammation. Immunology. 97: 232-240.
Lee, Y.L., Fu, C.L., Ye, Y.L. and Chiang, B.L. (1999b) Administration of interleukin-12 prevents mite Der p 1 allergen-IgE antibody production and airway eosinophil infiltration in an animal model of airway inflammation. Scand J Immunol. 49: 229-236.
Lee, Y.L., Ye, Y.L., Yu, C.I., Wu, Y.L., Lai, Y.L., Ku, P.H., et al (2001) Construction of single-chain interleukin-12 DNA plasmid to treat airway hyperresponsiveness in an animal model of asthma. Hum Gene Ther. 12: 2065-2079.
Leong, K.P. and Huston, D.P. (2001) Understanding the pathogenesis of allergic asthma using mouse models. Ann Allergy Asthma Immunol. 87: 96-109; quiz 110.
Li, L., Xia, Y., Nguyen, A., Lai, Y.H., Feng, L., Mosmann, T.R. and Lo, D. (1999) Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J Immunol. 162: 2477-2487.
Li, X.M., Chopra, R.K., Chou, T.Y., Schofield, B.H., Wills-Karp, M. and Huang, S.K. (1996) Mucosal IFN-gamma gene transfer inhibits pulmonary allergic responses in mice. J Immunol. 157: 3216-3219.
Lin, Y.L., Lee, S.S., Hou, S.M. and Chiang, B.L. (2006) Polysaccharide purified from Ganoderma lucidum induces gene expression changes in human dendritic cells and promotes T helper 1 immune response in BALB/c mice. Mol Pharmacol. 70: 637-644.
Liu, Y.J., Kanzler, H., Soumelis, V. and Gilliet, M. (2001) Dendritic cell lineage, plasticity and cross-regulation. Nat Immunol. 2: 585-589.
Macatonia, S.E., Hosken, N.A., Litton, M., Vieira, P., Hsieh, C.S., Culpepper, J.A., et al (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol. 154: 5071-5079.
Manetti, R., Parronchi, P., Giudizi, M.G., Piccinni, M.P., Maggi, E., Trinchieri, G. and Romagnani, S. (1993) Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med. 177: 1199-1204.
Marshall, J.D., Secrist, H., DeKruyff, R.H., Wolf, S.F. and Umetsu, D.T. (1995) IL-12 inhibits the production of IL-4 and IL-10 in allergen-specific human CD4+ T lymphocytes. J Immunol. 155: 111-117.
Martin, J.G., Shalaby, K. and Michoud, M.C. (2006) Immunotherapy as a disease modifier. Paediatr Respir Rev. 7 Suppl 1: S106-107.
Moore, K.W., de Waal Malefyt, R., Coffman, R.L. and O''Garra, A. (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 19: 683-765.
Mould, A.W., Matthaei, K.I., Young, I.G. and Foster, P.S. (1997) Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice. J Clin Invest. 99: 1064-1071.
Nadel, J.A. and Busse, W.W. (1998) Asthma. Am J Respir Crit Care Med. 157: S130-138.
Nakajima, H., Nakao, A., Watanabe, Y., Yoshida, S. and Iwamoto, I. (1994) IFN-alpha inhibits antigen-induced eosinophil and CD4+ T cell recruitment into tissue. J Immunol. 153: 1264-1270.
Piccinni, M.P., Maggi, E. and Romagnani, S. (2000) Environmental factors favoring the allergen-specific Th2 response in allergic subjects. Ann N Y Acad Sci. 917: 844-852.
Poole, J.A., Matangkasombut, P. and Rosenwasser, L.J. (2005) Targeting the IgE molecule in allergic and asthmatic diseases: review of the IgE molecule and clinical efficacy. J Allergy Clin Immunol. 115: S376-385.
Pulendran, B. (2005) Variegation of the immune response with dendritic cells and pathogen recognition receptors. J Immunol. 174: 2457-2465.
Racila, D.M. and Kline, J.N. (2005) Perspectives in asthma: molecular use of microbial products in asthma prevention and treatment. J Allergy Clin Immunol. 116: 1202-1205.
Rankin, S.M., Conroy, D.M. and Williams, T.J. (2000) Eotaxin and eosinophil recruitment: implications for human disease. Mol Med Today. 6: 20-27.
Rautava, S., Ruuskanen, O., Ouwehand, A., Salminen, S. and Isolauri, E. (2004) The hygiene hypothesis of atopic disease--an extended version. J Pediatr Gastroenterol Nutr. 38: 378-388.
Schleimer, R.P., Sterbinsky, S.A., Kaiser, J., Bickel, C.A., Klunk, D.A., Tomioka, K., et al (1992) IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J Immunol. 148: 1086-1092.
Schwarze, J., Hamelmann, E., Bradley, K.L., Takeda, K. and Gelfand, E.W. (1997) Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen. J Clin Invest. 100: 226-233.
Schwarze, J., Hamelmann, E., Cieslewicz, G., Tomkinson, A., Joetham, A., Bradley, K. and Gelfand, E.W. (1998) Local treatment with IL-12 is an effective inhibitor of airway hyperresponsiveness and lung eosinophilia after airway challenge in sensitized mice. J Allergy Clin Immunol. 102: 86-93.
Secrist, H., Chelen, C.J., Wen, Y., Marshall, J.D. and Umetsu, D.T. (1993) Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med. 178: 2123-2130.
Shimizu, T., Mochizuki, H. and Morikawa, A. (1997) Effect of influenza A virus infection on acid-induced cough response in children with asthma. Eur Respir J. 10: 71-74.
Sigurs, N., Gustafsson, P.M., Bjarnason, R., Lundberg, F., Schmidt, S., Sigurbergsson, F. and Kjellman, B. (2005) Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med. 171: 137-141.
Snapper, C.M. and Paul, W.E. (1987) Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 236: 944-947.
Stampfli, M.R., Scott Neigh, G., Wiley, R.E., Cwiartka, M., Ritz, S.A., Hitt, M.M., (1999) Regulation of allergic mucosal sensitization by interleukin-12 gene transfer to the airway. Am J Respir Cell Mol Biol. 21: 317-326.
Steinbrink, K., Wolfl, M., Jonuleit, H., Knop, J. and Enk, A.H. (1997) Induction of tolerance by IL-10-treated dendritic cells. J Immunol. 159: 4772-4780.
Sung, S., Rose, C.E. and Fu, S.M. (2001) Intratracheal priming with ovalbumin- and ovalbumin 323-339 peptide-pulsed dendritic cells induces airway hyperresponsiveness, lung eosinophilia, goblet cell hyperplasia, and inflammation. J Immunol. 166: 1261-1271.
Sur, S., Lam, J., Bouchard, P., Sigounas, A., Holbert, D. and Metzger, W.J. (1996) Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. J Immunol. 157: 4173-4180.
Sur, S., Wild, J.S., Choudhury, B.K., Sur, N., Alam, R. and Klinman, D.M. (1999) Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol. 162: 6284-6293.
Swain, S.L., Weinberg, A.D., English, M. and Huston, G. (1990) IL-4 directs the development of Th2-like helper effectors. J Immunol. 145: 3796-3806.
Tournoy, K.G., Kips, J.C. and Pauwels, R.A. (2002) Is Th1 the solution for Th2 in asthma? Clin Exp Allergy. 32: 17-29.
Trinchieri, G. (1994) Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood. 84: 4008-4027.
Valenta, R. (2002) The future of antigen-specific immunotherapy of allergy. Nat Rev Immunol. 2: 446-453.
von Hertzen, L.C. and Haahtela, T. (2000) Could the risk of asthma and atopy be reduced by a vaccine that induces a strong T-helper type 1 response? Am J Respir Cell Mol Biol. 22: 139-142.
Woolcock, A.J. and Peat, J.K. (1997) Evidence for the increase in asthma worldwide. Ciba Found Symp. 206: 122-134
Wu, C., Yang, G., Bermudez-Humaran, L.G., Pang, Q., Zeng, Y., Wang, J. and Gao, X. (2006) Immunomodulatory effects of IL-12 secreted by Lactococcus lactis on Th1/Th2 balance in ovalbumin (OVA)-induced asthma model mice. Int Immunopharmacol. 6: 610-615.
Ye, Y.L., Huang, W.C., Lee, Y.L. and Chiang, B.L. (2002) Interleukin-12 inhibits eotaxin secretion of cultured primary lung cells and alleviates airway inflammation in vivo. Cytokine. 19: 76-84.
Ye, Y.L., Lee, Y.L., Chuang, Z.J., Lai, H.J., Chen, C.C., Tao, M.H. and Chiang, B.L. (2004) Dendritic cells modulated by cytokine-expressing adenoviruses alleviate eosinophilia and airway hyperresponsiveness in an animal model of asthma. J Allergy Clin Immunol. 114: 88-96.
Yoshimoto, T., Okamura, H., Tagawa, Y.I., Iwakura, Y. and Nakanishi, K. (1997) Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Proc Natl Acad Sci U S A. 94: 3948-3953.
Zhao, L.L., Linden, A., Sjostrand, M., Cui, Z.H., Lotvall, J. and Jordana, M. (2000) IL-12 regulates bone marrow eosinophilia and airway eotaxin levels induced by airway allergen exposure. Allergy. 55: 749-756.

Chiu, S. T. (1996). Notes on the genus Taxillus Van Tieghem（Loranthaceae）in Taiwan. Taiwania 41, 154-167.

劉業經, 呂福原, 歐辰雄, 陳堃霖, (1988). 台灣產桑寄生科植物分類之研究. 中華林學季刊 21, 3-24.

邱少婷, (1998). 桑寄生植物生活史與台灣桑寄生植物的多樣性.海峽兩岸植物多樣性與保育, 國立自然科學博物館編印 255-268.

陳堃霖, (1987). 台灣桑寄生科分類之研究.國立中興大學森林研究所碩士論文

王禹力, (2005). 忍冬葉桑寄生之化學成分與生物活性研究. 長庚大學天然藥物研究所碩士論文