進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-1808201412315200
論文名稱(中文) 水溶性幾丁聚醣抑制神經生長因子改善塵螨過敏鼻炎
論文名稱(英文) Water soluble chitosan inhibits nerve growth factor in murine model of house dust mite induced allergic rhinitis
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 102
學期 2
出版年 103
研究生(中文) 陳佩琪
研究生(英文) Pei-Chi Chen
學號 S46014124
學位類別 碩士
語文別 英文
論文頁數 64頁
口試委員 口試委員-楊倍昌
口試委員-葉才明
口試委員-洪志興
指導教授-王志堯
中文關鍵字 塵螨  過敏性鼻炎  神經生長因子  水溶性幾丁聚醣 
英文關鍵字 house dust mite  allergic rhinitis  nerve growth factor  water soluble chitosan 
學科別分類
中文摘要 過敏性鼻炎是一種成因很複雜的上呼吸道疾病。它可能是一種由黏膜性發炎及呼吸道過度反應所造成的疾病。現今也有越來越多的研究顯示,神經生長因子 (nerve growth factor, NGF),是對於神經生長及活化很重要的神經營養蛋白 (neurotrophin) 家族成員之一,他們能夠做為免疫細胞和神經系統之間訊息雙向傳遞的調控因子,同時也有研究指出神經生長因子能夠增強原本已經存在的TH2免疫反應。另外,水溶性幾丁聚醣 (water-soluble chitosan, WSC) 也被證實具有抑制發炎的特性,因此本篇研究致力於探討在家塵螨 (Dermatophagoides pteronyssinus, Der p)所引起的過敏性鼻炎小鼠模式中,神經生長因子所扮演的角色,更進一步評估水溶性幾丁聚醣應用在抗過敏性鼻炎的效果及作用機制。實驗結果顯示,小鼠受到過敏原刺激後,血清當中免疫球蛋白E (IgE)的表現量上升,而且也引起上呼吸道過度反應,同時Der p也誘發小鼠鼻腔表達高表現量的神經生長因子以及其專一性酪氨酸激酶受器(Tyrosine kinase receptor A, TrkA)以及神經營養蛋白低親和力受體 (p75 neurotrophin receptor, p75NTR),而且也引起鼻腔局部TH2所調控過敏免疫反應包括引起嗜酸性球及活化的肥大細胞浸潤並且促進相關的細胞激素分泌;以鼻腔滴入式給予水溶性幾丁聚醣後,原本由過敏原所引起的過敏性發炎及上呼吸道過度反應皆受到抑制。為了進一步確認其中的相關機制,我們以神經生長因子及TH2免疫相關的細胞激素IL-13重組蛋白刺激人類鼻腔上皮細胞株 (RPMI-2650)。從西方墨點法的結果得知,神經生長因子及過敏性TH2免疫系統會相互調控,引起加成反應進而促進鼻腔上皮過敏性發炎。水溶性幾丁聚醣的預防性治療,雖然不能抑制過敏性TH2免疫反應卻能透過抑制神經生長因子的生成及功能緩和過敏性發炎。直接用過敏原Der p刺激細胞的實驗中也可以得到類似的結論,因此水溶性幾丁聚醣具有抗過敏性鼻炎的治療潛力。
英文摘要 Allergic rhinitis (AR) is a disease with symptom of nasal airway hyperresponsiveness and mucosal inflammation mediated by IgE-associated processes. Nerve growth factor (NGF), a neurotrophin, has been shown to play an important role in neuroimmune responses by augmenting an existing type 2 T helper cell (TH2) immune response. Since chitin exhibits anti-inflammatory properties by inhibiting the development of allergic TH2 response, we aimed to assess the effect of the soluble derivatives of chitin—water soluble chitosan (WSC) on the NGF in a mouse model of Dermatophagoides pteronyssinus (Der p)-induced AR. First, we established an NGF-mediated AR toward augmenting systemic total and Der p-specific IgE levels, upper airway hyperresponsiveness, and local TH2 related immune response including the infiltration of eosinophils and degranulation of mast cells as well as TH2 related cytokines production in the nasal septum and nasal cavity lavage fluids. Interestingly, intranasal administration of WSC reduced allergic inflammation and improved the upper airway hyperresponsiveness. The expression of NGF and its related low affinity p75 neurotrophin receptors (p75NTR) as well as high affinity tyrosine kinase receptor A (TrkA) recptors in nasal epithelium of Der p-stimulated mice also repressed. Next, we used human nasal septum epithelial cell line (RPMI-2650) to investigate the detail mechanisms of candidate anti-allergic agents—WSC in attenuating Der p-induced airway inflammation. The results showed that NGF and TH2 related cytokines create an amplification loop resulting in broader allergic inflammation in upper-airway epithelial cells. In addition, WSC attenuated allergic inflammation and the epithelial cells damage through inhibiting NGF biosynthesis during allergic TH2 immune responses. In summary, we have demonstrated the role of NGF in a mouse model of house dust mite-induced AR, and the therapeutic effect of WSC in our AR mouse model, may through the attenuation NGF-induced airway inflammation as well as the inhibition of NGF synthesis. Our finding provides a new therapeutic modality of patients suffered with AR in clinical condition.
論文目次 誌謝 I
中文摘要 II
Abstract IV
Abbreviation VI
Contents VIII
Figure List X
Introduction 1
General introduction of allergic rhinitis 1
The immune response to allergic rhinitis 2
The association between nerve growth factor and allergic rhinitis 5
Characteristics and biological function of water soluble chitosan 8
Hypothesis of the study 9
Material and Methods 11
In vivo murine model of allergic rhinitis and treatment 11
Reagents 12
Measuring of the nasal response by a noninvasive Enhanced Pause System 12
Collection of nasal lavage fluids (NLF) 12
Measurement of total and Der p specific IgE in serum 13
Histopathology analysis 13
Histological analysis of eosinophils 14
Histological analysis of mast cells 14
Measurement of NGF, BDNF and cytokines in NLF 15
Immunohistochemistry 17
In vitro model of allergic rhinitis and treatment 17
Western blot analysis of TSLP, NGF, TrkA, and p75NTR expression in cell lines 18
Statistical analysis 19
Results 20
Intranasal challenge with Der p extract induced the hallmarks of allergic rhinitis in expereimental mouse model 20
NGF mediated the nasal mucosal inflammation in the mouse model of Der p-induced allergic rhinitis 21
Intranasal administration of WSC inhibited NGF-mediated local inflammation in Der p-induced allergic rhinitis mouse model 23
WSC inhibited NGF biosynthesis and function in nasal epithelium to alleviate inflammation 24
Discussion 26
References 31
Figures 39
參考文獻 Addo-Yobo, E. O., Custovic, A., Taggart, S. C., Craven, M., Bonnie, B., & Woodcock, A. (2001). Risk factors for asthma in urban Ghana. J Allergy Clin Immunol, 108(3), 363-368.
Al-Shami, A., Spolski, R., Kelly, J., Keane-Myers, A., & Leonard, W. J. (2005). A role for TSLP in the development of inflammation in an asthma model. J Exp Med, 202(6), 829-839.
Angkasekwinai, P., Park, H., Wang, Y. H., Wang, Y. H., Chang, S. H., Corry, D. B., Dong, C. (2007). Interleukin 25 promotes the initiation of proallergic type 2 responses. J Exp Med, 204(7), 1509-1517.
Ballantyne, S. J., Barlow, J. L., Jolin, H. E., Nath, P., Williams, A. S., Chung, K. F., McKenzie, A. N. (2007). Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol, 120(6), 1324-1331.
Barde, Y. A. (1990). The nerve growth factor family. Prog Growth Factor Res, 2(4), 237-248.
Bibel, M., Hoppe, E., & Barde, Y. A. (1999). Biochemical and functional interactions between the neurotrophin receptors trk and p75NTR. EMBO J, 18(3), 616-622.
Bonini, S., Lambiase, A., Bonini, S., Angelucci, F., Magrini, L., Manni, L., & Aloe, L. (1996). Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma. Proc Natl Acad Sci U S A, 93(20), 10955-10960.
Bonini, S., Rasi, G., Bracci-Laudiero, M. L., Procoli, A., & Aloe, L. (2003). Nerve Growth Factor: Neurotrophin or Cytokine? International Archives of Allergy and Immunology, 131(2), 80-84.
Braunstahl, G. J. (2009). United airways concept: what does it teach us about systemic inflammation in airways disease? Proc Am Thorac Soc, 6(8), 652-654.
Braunstahl, G. J., Fokkens, W. J., Overbeek, S. E., KleinJan, A., Hoogsteden, H. C., & Prins, J. B. (2003). Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways. Clin Exp Allergy, 33(5), 579-587.
Bresciani, M., Laliberte, F., Laliberte, M. F., Gramiccioni, C., & Bonini, S. (2009). Nerve growth factor localization in the nasal mucosa of patients with persistent allergic rhinitis. Allergy, 64(1), 112-117.
Chen, Y. L., Huang, H. Y., Lee, C. C., & Chiang, B. L. (2014). Small interfering RNA targeting nerve growth factor alleviates allergic airway hyperresponsiveness. Mol Ther Nucleic Acids, 3, e158.
Curotto de Lafaille, M. A., Lafaille, J. J., & Graca, L. (2010). Mechanisms of tolerance and allergic sensitization in the airways and the lungs. Curr Opin Immunol, 22(5), 616-622.
De Vries, A., Engels, F., Henricks, P. A., Leusink-Muis, T., Fischer, A., & Nijkamp, F. P. (2002). Antibodies directed against nerve growth factor inhibit the acute bronchoconstriction due to allergen challenge in guinea-pigs. Clin Exp Allergy, 32(2), 325-328.
Dechant, G., Biffo, S., Okazawa, H., Kolbeck, R., Pottgiesser, J., & Barde, Y. A. (1993). Expression and binding characteristics of the BDNF receptor chick trkB. Development, 119(2), 545-558.
Delcroix, J. D., Valletta, J., Wu, C., Howe, C. L., Lai, C. F., Cooper, J. D., Mobley, W. C. (2004). Trafficking the NGF signal: implications for normal and degenerating neurons. Prog Brain Res, 146, 3-23.
Dykewicz, M. S., Fineman, S., & Skoner, D. P. (1998). Joint Task Force summary statements on Diagnosis and Management of Rhinitis. Ann Allergy Asthma Immunol, 81, 474-477.
Esposito, D., Patel, P., Stephens, R. M., Perez, P., Chao, M. V., Kaplan, D. R., & Hempstead, B. L. (2001). The cytoplasmic and transmembrane domains of the p75 and Trk A receptors regulate high affinity binding to nerve growth factor. J Biol Chem, 276(35), 32687-32695.
Fernandez-Caldas, E., Baena-Cagnani, C. E., Lopez, M., Patino, C., Neffen, H. E., Sanchez-Medina, M., et al. (1993). Cutaneous sensitivity to six mite species in asthmatic patients from five Latin American countries. J Investig Allergol Clin Immunol, 3(5), 245-249.
Fischer, T. C., Lauenstein, H. D., Serowka, F., Pilzner, C., Groneberg, D. A., & Welker, P. (2008). Pan-neurotrophin receptor p75NTR expression is strongly induced in lesional atopic mast cells. Clin Exp Allergy, 38(7), 1168-1173.
Fox, A. J., Patel, H. J., Barnes, P. J., & Belvisi, M. G. (2001). Release of nerve growth factor by human pulmonary epithelial cells: role in airway inflammatory diseases. Eur J Pharmacol, 424(2), 159-162.
Freund, V., & Frossard, N. (2004). Expression of nerve growth factor in the airways and its possible role in asthma. Prog Brain Res, 146, 335-346.
Gauchat, J. F., Henchoz, S., Mazzei, G., Aubry, J. P., Brunner, T., Blasey, H., et al. (1993). Induction of human IgE synthesis in B cells by mast cells and basophils. Nature, 365(6444), 340-343.
Hackett, T. L., de Bruin, H. G., Shaheen, F., van den Berge, M., van Oosterhout, A. J., Postma, D. S., & Heijink, I. H. (2013). Caveolin-1 controls airway epithelial barrier function. Implications for asthma. Am J Respir Cell Mol Biol, 49(4), 662-671.
Hallstrand, T. S., Hackett, T. L., Altemeier, W. A., Matute-Bello, G., Hansbro, P. M., & Knight, D. A. (2014). Airway epithelial regulation of pulmonary immune homeostasis and inflammation. Clin Immunol, 151(1), 1-15.
Hamada, A., Watanabe, N., Ohtomo, H., & Matsuda, H. (1996). Nerve growth factor enhances survival and cytotoxic activity of human eosinophils. Br J Haematol, 93(2), 299-302.
Heinzerling, L. M., Burbach, G. J., Edenharter, G., Bachert, C., Bindslev-Jensen, C., Bonini, S., Zuberbier, T. (2009). GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe. Allergy, 64(10), 1498-1506.
Holgate, S. T., & Broide, D. (2003). New targets for allergic rhinitis--a disease of civilization. Nat Rev Drug Discov, 2(11), 902-914.
Holt, P. G., Strickland, D. H., Wikstrom, M. E., & Jahnsen, F. L. (2008). Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol, 8(2), 142-152.
Horigome, K., Pryor, J. C., Bullock, E. D., & Johnson, E. M., Jr. (1993). Mediator release from mast cells by nerve growth factor. Neurotrophin specificity and receptor mediation. J Biol Chem, 268(20), 14881-14887.
Hoyle, G. W., Graham, R. M., Finkelstein, J. B., Nguyen, K. P., Gozal, D., & Friedman, M. (1998). Hyperinnervation of the airways in transgenic mice overexpressing nerve growth factor. Am J Respir Cell Mol Biol, 18(2), 149-157.
Jacquet, A. (2011). Interactions of airway epithelium with protease allergens in the allergic response. Clin Exp Allergy, 41(3), 305-311.
Jayakumar, R., Nwe, N., Tokura, S., & Tamura, H. (2007). Sulfated chitin and chitosan as novel biomaterials. Int J Biol Macromol, 40(3), 175-181.
Jutel, M., Watanabe, T., Klunker, S., Akdis, M., Thomet, O. A., Malolepszy, J., Akdis, C. A. (2001). Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature, 413(6854), 420-425.
Kassel, O., de Blay, F., Duvernelle, C., Olgart, C., Israel-Biet, D., Krieger, P., Frossard, N. (2001). Local increase in the number of mast cells and expression of nerve growth factor in the bronchus of asthmatic patients after repeated inhalation of allergen at low-dose. Clin Exp Allergy, 31(9), 1432-1440.
Kerzel, S., Path, G., Nockher, W. A., Quarcoo, D., Raap, U., Groneberg, D. A., Renz, H. (2003). Pan-neurotrophin receptor p75 contributes to neuronal hyperreactivity and airway inflammation in a murine model of experimental asthma. Am J Respir Cell Mol Biol, 28(2), 170-178.
Lambiase, A., Micera, A., Sgrulletta, R., Bonini, S., & Bonini, S. (2004). Nerve growth factor and the immune system: old and new concepts in the cross-talk between immune and resident cells during pathophysiological conditions. Curr Opin Allergy Clin Immunol, 4(5), 425-430.
Lambrecht, B. N. (2001). Allergen uptake and presentation by dendritic cells. Curr Opin Allergy Clin Immunol, 1(1), 51-59.
Lee, C. G. (2009). Chitin, chitinases and chitinase-like proteins in allergic inflammation and tissue remodeling. Yonsei Med J, 50(1), 22-30.
Leung, R., & Ho, P. (1994). Asthma, allergy, and atopy in three south-east Asian populations. Thorax, 49(12), 1205-1210.
Li, J., Sun, B., Huang, Y., Lin, X., Zhao, D., Tan, G., Zhong, N. (2009). A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China. Allergy, 64(7), 1083-1092.
Madhumathi, K., Binulal, N. S., Nagahama, H., Tamura, H., Shalumon, K. T., Selvamurugan, N., Jayakumar, R. (2009). Preparation and characterization of novel beta-chitin-hydroxyapatite composite membranes for tissue engineering applications. Int J Biol Macromol, 44(1), 1-5.
Madhumathi, K., Sudheesh Kumar, P. T., Abhilash, S., Sreeja, V., Tamura, H., Manzoor, K., Jayakumar, R. (2010). Development of novel chitin/nanosilver composite scaffolds for wound dressing applications. J Mater Sci Mater Med, 21(2), 807-813.
Mandhane, S. N., Shah, J. H., & Thennati, R. (2011). Allergic rhinitis: an update on disease, present treatments and future prospects. Int Immunopharmacol, 11(11), 1646-1662.
Mao, H. Q., Roy, K., Troung-Le, V. L., Janes, K. A., Lin, K. Y., Wang, Y., Leong, K. W. (2001). Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J Control Release, 70(3), 399-421.
Meakin, S. O., & Shooter, E. M. (1992). The nerve growth factor family of receptors. Trends Neurosci, 15(9), 323-331.
Min, Y. G. (2010). The pathophysiology, diagnosis and treatment of allergic rhinitis. Allergy Asthma Immunol Res, 2(2), 65-76.
Miraglia Del Giudice, M., Pedulla, M., Piacentini, G. L., Capristo, C., Brunese, F. P., Decimo, F., Capristo, A. F. (2002). Atopy and house dust mite sensitization as risk factors for asthma in children. Allergy, 57(2), 169-172.
Nakaya, M., Dohi, M., Okunishi, K., Nakagome, K., Tanaka, R., Imamura, M., Kaga, K. (2006). Noninvasive system for evaluating allergen-induced nasal hypersensitivity in murine allergic rhinitis. Lab Invest, 86(9), 917-926.
Nishimura, K., Nishimura, S., Nishi, N., Saiki, I., Tokura, S., & Azuma, I. (1984). Immunological activity of chitin and its derivatives. Vaccine, 2(1), 93-99.
Nockher, W. A., & Renz, H. (2006). Neurotrophins in allergic diseases: from neuronal growth factors to intercellular signaling molecules. J Allergy Clin Immunol, 117(3), 583-589.
Noga, O., Englmann, C., Hanf, G., Grutzkau, A., Guhl, S., & Kunkel, G. (2002). Activation of the specific neurotrophin receptors TrkA, TrkB and TrkC influences the function of eosinophils. Clin Exp Allergy, 32(9), 1348-1354.
Noga, O., Englmann, C., Hanf, G., Grutzkau, A., Seybold, J., & Kunkel, G. (2003). The production, storage and release of the neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 by human peripheral eosinophils in allergics and non-allergics. Clin Exp Allergy, 33(5), 649-654.
Obara, Y., & Nakahata, N. (2002). The Signaling Pathway of Neurotrophic Factor Biosynthesis. Drug News Perspect, 15(5), 290-298.
Path, G., Braun, A., Meents, N., Kerzel, S., Quarcoo, D., Raap, U., Renz, H. (2002). Augmentation of allergic early-phase reaction by nerve growth factor. Am J Respir Crit Care Med, 166(6), 818-826.
Peat, J. K., Tovey, E., Toelle, B. G., Haby, M. M., Gray, E. J., Mahmic, A., & Woolcock, A. J. (1996). House dust mite allergens. A major risk factor for childhood asthma in Australia. Am J Respir Crit Care Med, 153(1), 141-146.
Perzanowski, M. S., Ng'ang'a, L. W., Carter, M. C., Odhiambo, J., Ngari, P., Vaughan, J. W., Platts-Mills, T. A. (2002). Atopy, asthma, and antibodies to Ascaris among rural and urban children in Kenya. J Pediatr, 140(5), 582-588.
Prefontaine, D., Nadigel, J., Chouiali, F., Audusseau, S., Semlali, A., Chakir, J., Hamid, Q. (2010). Increased IL-33 expression by epithelial cells in bronchial asthma. J Allergy Clin Immunol, 125(3), 752-754.
Raap, U., & Braunstahl, G. J. (2010). The role of neurotrophins in the pathophysiology of allergic rhinitis. Curr Opin Allergy Clin Immunol, 10(1), 8-13.
Raap, U., Deneka, N., Bruder, M., Kapp, A., & Wedi, B. (2008). Differential up-regulation of neurotrophin receptors and functional activity of neurotrophins on peripheral blood eosinophils of patients with allergic rhinitis, atopic dermatitis and nonatopic subjects. Clin Exp Allergy, 38(9), 1493-1498.
Raap, U., Fokkens, W., Bruder, M., Hoogsteden, H., Kapp, A., & Braunstahl, G. J. (2008). Modulation of neurotrophin and neurotrophin receptor expression in nasal mucosa after nasal allergen provocation in allergic rhinitis. Allergy, 63(4), 468-475.
Runswick, S., Mitchell, T., Davies, P., Robinson, C., & Garrod, D. R. (2007). Pollen proteolytic enzymes degrade tight junctions. Respirology, 12(6), 834-842.
Ryu, J. H., Yoo, J. Y., Kim, M. J., Hwang, S. G., Ahn, K. C., Ryu, J. C., Yoon, J. H. (2013). Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways. J Allergy Clin Immunol, 131(2), 549-561.
Saenz, S. A., Taylor, B. C., & Artis, D. (2008). Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites. Immunol Rev, 226, 172-190.
Sanico, A. M., Stanisz, A. M., Gleeson, T. D., Bora, S., Proud, D., Bienenstock, J., Togias, A. (2000). Nerve growth factor expression and release in allergic inflammatory disease of the upper airways. Am J Respir Crit Care Med, 161(5), 1631-1635.
Sarin, S., Undem, B., Sanico, A., & Togias, A. (2006). The role of the nervous system in rhinitis. J Allergy Clin Immunol, 118(5), 999-1016.
Sawada, J., Itakura, A., Tanaka, A., Furusaka, T., & Matsuda, H. (2000). Nerve growth factor functions as a chemoattractant for mast cells through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways. Blood, 95(6), 2052-2058.
Sharkhuu, T., Matthaei, K. I., Forbes, E., Mahalingam, S., Hogan, S. P., Hansbro, P. M., & Foster, P. S. (2006). Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity. Clin Exp Allergy, 36(12), 1575-1583.
Shibata, Y., Foster, L. A., Bradfield, J. F., & Myrvik, Q. N. (2000). Oral administration of chitin down-regulates serum IgE levels and lung eosinophilia in the allergic mouse. J Immunol, 164(3), 1314-1321.
Shibata, Y., Foster, L. A., Metzger, W. J., & Myrvik, Q. N. (1997). Alveolar macrophage priming by intravenous administration of chitin particles, polymers of N-acetyl-D-glucosamine, in mice. Infect Immun, 65(5), 1734-1741.
Shibata, Y., Honda, I., Justice, J. P., Van Scott, M. R., Nakamura, R. M., & Myrvik, Q. N. (2001). Th1 adjuvant N-acetyl-D-glucosamine polymer up-regulates Th1 immunity but down-regulates Th2 immunity against a mycobacterial protein (MPB-59) in interleukin-10-knockout and wild-type mice. Infect Immun, 69(10), 6123-6130.
Skoner, D. P. (2001). Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol, 108(1 Suppl), S2-8.
Sur, S., Lam, J., Bouchard, P., Sigounas, A., Holbert, D., & Metzger, W. J. (1996). Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. J Immunol, 157(9), 4173-4180.
Takhar, P., Smurthwaite, L., Coker, H. A., Fear, D. J., Banfield, G. K., Carr, V. A., Gould, H. J. (2005). Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis. J Immunol, 174(8), 5024-5032.
Tang, H., Cao, W., Kasturi, S. P., Ravindran, R., Nakaya, H. I., Kundu, K., Pulendran, B. (2010). The T helper type 2 response to cysteine proteases requires dendritic cell-basophil cooperation via ROS-mediated signaling. Nat Immunol, 11(7), 608-617.
Thomas, W. R. (2010). Geography of house dust mite allergens. Asian Pac J Allergy Immunol, 28(4), 211-224.
Togias, A. (2004). Systemic effects of local allergic disease. J Allergy Clin Immunol, 113(1 Suppl), S8-14.
Togias, Alkis. (2000). Unique mechanistic features of allergic rhinitis. Journal of Allergy and Clinical Immunology, 105(6), S599-S604.
Toyoda, M., Nakamura, M., Makino, T., Hino, T., Kagoura, M., & Morohashi, M. (2002). Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. Br J Dermatol, 147(1), 71-79.
Turner, H., & Kinet, J. P. (1999). Signalling through the high-affinity IgE receptor Fc epsilonRI. Nature, 402(6760 Suppl), B24-30.
Wang, J. Y. (2013). The innate immune response in house dust mite-induced allergic inflammation. Allergy Asthma Immunol Res, 5(2), 68-74.
Wang, J. Y., & Chen, W. Y. (1992). Inhalant allergens in asthmatic children in Taiwan: comparison evaluation of skin testing, radioallergosorbent test and multiple allergosorbent chemiluminescent assay for specific IgE. J Formos Med Assoc, 91(12), 1127-1132.
Wihl, J. A., & Malm, L. (1988). Rhinomanometry and nasal peak expiratory and inspiratory flow rate. Ann Allergy, 61(1), 50-55.
Williams, C. M., & Galli, S. J. (2000). The diverse potential effector and immunoregulatory roles of mast cells in allergic disease. J Allergy Clin Immunol, 105(5), 847-859.
Wu, X., Myers, A. C., Goldstone, A. C., Togias, A., & Sanico, A. M. (2006). Localization of nerve growth factor and its receptors in the human nasal mucosa. J Allergy Clin Immunol, 118(2), 428-433.
Xiang, Z., & Nilsson, G. (2000). IgE receptor-mediated release of nerve growth factor by mast cells. Clin Exp Allergy, 30(10), 1379-1386.
Ye, Y. L., Wu, H. T., Lin, C. F., Hsieh, C. Y., Wang, J. Y., Liu, F. H., Tsao, C. W. (2011). Dermatophagoides pteronyssinus 2 regulates nerve growth factor release to induce airway inflammation via a reactive oxygen species-dependent pathway. Am J Physiol Lung Cell Mol Physiol, 300(2), L216-224.
Yousef, M., Pichyangkura, R., Soodvilai, S., Chatsudthipong, V., & Muanprasat, C. (2012). Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: therapeutic efficacy and possible mechanisms of action. Pharmacol Res, 66(1), 66-79.
Zhou, B., Comeau, M. R., De Smedt, T., Liggitt, H. D., Dahl, M. E., Lewis, D. B., Ziegler, S. F. (2005). Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat Immunol, 6(10), 1047-1053.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2024-12-31起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw