臺灣博碩士論文加值系統

過敏反應為人體免疫系統對外來物質產生之過度免疫反應，包括過敏性鼻炎、皮膚炎、氣喘等。過敏疾病為現今普遍疾病，臺灣過敏患者約佔總人口數33%。
甘藍 (Brassica oleracea var. capitata L.) 為台灣冬季廣泛栽種之蔬菜，具多種生理活性包括抗發炎、抗氧化、抗癌等。本論文以體外試驗模式，以IgE (immunoglobulin E, IgE) 致敏/DNP-HSA (dinitrophenyl-human serum albumin, DNP-HSA) 抗原之RBL-2H3大鼠嗜鹼性白血病細胞，探討甘藍95%乙醇萃取物之抗過敏功效及相關調節機轉。
研究結果顯示，大鼠嗜鹼性白血病細胞RBL-2H3經IgE抗體致敏/DNP-HSA抗原作用，活化Syk→LAT路徑，繼而磷酸化mitogen-activated protein kinase (MAPK) 家族 (ERK、JNK及p-38) 及Akt蛋白，進而轉錄及轉譯出細胞激素 (TNF-α、IL-4及IL-10) 與發炎相關物質 (cyclooxygenase-2, COX-2)。亦使細胞質鈣離子濃度上升，導致細胞之脫顆粒 (degranulation) 作用及發炎相關物質生成。甘藍95%乙醇萃取物 (312.5~625 μg/mL) 顯著抑制訊息傳導蛋白 (p-Syk、p-LAT、p-Akt、p-ERK、p-JNK及p-p38等) 表現，為處理控制組之44~81%；並減少下游發炎相關因子 (COX-2、TNF-α、IL-4、IL-10等) 之生成，使過敏反應之發炎現象受抑制。甘藍95%乙醇萃取物 (312.5~625 μg/mL) 亦抑制Syk→LAT→PLCγ→IP3R路徑，顯著減少細胞質鈣離子濃度，繼而抑制細胞之β-hexosaminidase釋放及發炎相關物質之生成。本研究結果顯示出，甘藍95%乙醇萃取物具調節IgE致敏之第I型過敏反應之活性，具高度潛力開發成為抗過敏之保健食品。

Allergy is an over-response human immune disease due to foreign substances, including allergic rhinitis, dermatitis, asthma, and others. Allergic disease is a common disease, which influences 33% Taiwanese population approximately.
Cabbage (Brassica oleracea var. capitata L.) is widely cultivated in Taiwan, which exhibits mutiple biological activities including anti-inflammation, anti-oxidative reaction and anti-cancer activity. In this study, we investigated anti-allergic effects and the relevant mechanisms of 95% ethanol Brassica oleracea var. capitata L extract in the immunoglobulin E (IgE) sensitized and dinitrophenyl-human serum albumin (DNP-HSA) stimulated rat basophlic leukemia RBL-2H3 cells.
In the results, RBL-2H3 cells was sensitized by IgE and stimulated with DNP-HSA, the Syk→LAT pathway was activated followed by the mitogen-activated protein kinase (MAPK) family (ERK、JNK and p-38) and Akt phosphorylation. These proteins translocated into nucleus to transcribe and translate cyotokines (TNF-α、IL-4 and IL-10) and inflammatory factors (cyclooxygenase-2, COX-2). On the other side, IgE sensitization and DNP-HSA stimulation for RBL-2H3 cells resulted in cytosolic calcium ion concentration dramtically increasing followed by degranulation and inflammatory factor production. 95% Ethanol Brassica oleracea var. capitata L. extracts (312.5~625 μg/mL) significantly inhibited signaling transduction protein expressions (p-Syk、p-LAT、p-Akt、p-ERK、p-JNK and p-p38), 44~81% of that of treatment control (0 μg extract/mL). Thus, the downstream inflammatory factors (TNF-α、IL-4 and IL-10) decreased followed by inflammation response reduced. 95% Ethanol Brassica oleracea var. capitata L. extract (312.5~625 μg/mL) also inhibited Syk→LAT→PLCγ→IP3R pathway activation, which in turn decreased elevation of the intracellular Ca2+ concentration. Thus, the β-hexosaminidase release and inflammatory relevant factor production in RBL-2H3 cells were effectively inhibited. In this study, 95% ethanol Brassica oleracea var. capitata L. extracts possess high ability to regulate IgE sensitized type I allergy, exhibiting great potential to be an anti-allergic health supplements.

中文摘要 i
Abstract ii
目次 iv
附圖次 vii
附表次 viii
圖次 ix
表次 x
縮寫表 xi
壹、前言 1
貳、文獻回顧 2
一、免疫系統功能 2
(一) 先天性免疫 2
(二) 適應性免疫 3
(三) TH1/TH2平衡與疾病關係 3
(四) 過度免疫反應 (hypersensitivity) 4
二、過敏反應之參與因子與類型 5
(一) 過敏反應參與因子 6
(二) 過敏反應類型 7
三、過敏反應之致病機轉及訊息傳導 10
(一) 致病機轉 10
(二) 細胞訊息傳導 13
四、過敏反應之治療方式 18
(一) 皮質類固醇 (corticosteroid) 18
(二) β2-腎上腺素受體作用劑 (β2-adrenoceptor agonist) 19
(三) 介質拮抗劑與合成抑制劑 (mediator antagonist and synthesis inhibitor) 19
(四) 專一性過敏原免疫療法 (allergen-specific immunotherapy, SIT) 19
(五) 細胞激素免疫療法 (cytokine-based immunotherapy) 21
五、甘藍 (Brassica oleracea var. capitata L.) 21
(一) 甘藍之生長地區及食用性 21
(二) 成分 22
(三) 生理活性 22
參、研究目的 27
肆、研究架構 28
伍、材料與方法 29
一、儀器 29
二、細胞株 29
(一) 細胞來源 29
(二) 細胞活化 30
(三) 細胞繼代 31
(四) 細胞保存 31
三、甘藍 (Brassica oleracea var. capitata L.) 32
(一) 甘藍來源及處理 32
(二) 甘藍粉末水分含量測定 32
(三) 甘藍95%乙醇萃取物製備 32
四、甘藍95%乙醇萃取物對RBL-2H3細胞存活率分析 34
(一) 藥品配製 34
(二) 細胞存活率 (viability) 分析 34
五、甘藍95%乙醇萃取物對IgE致敏DNP-HSA抗原刺激RBL-2H3細胞之β-hexosaminidase釋放分析 34
(一) 藥品配製 34
(二) RBL-2H3細胞之抗體、抗原及藥物處理 36
(三) β-Hexosaminidase釋放分析 36
六、甘藍95%乙醇萃取物對IgE致敏DNP-HSA抗原刺激RBL-2H3細胞之細胞質鈣離子濃度測定 36
(一) 藥品配製 37
(二) RBL-2H3細胞經抗體、抗原及藥物處理 37
七、甘藍95%乙醇萃取物對細胞質鈣離子調控RBL-2H3細胞之β-hexosaminidase釋放分析 38
(一) 藥品配製 38
(二) RBL-2H3細胞之藥物處理 38
(三) β-Hexosaminidase釋放分析 39
八、甘藍95%乙醇萃取物對IgE致敏及DNP-HSA抗原刺激之RBL-2H3細胞之蛋白表現分析〜西方墨點法 (Western blot).39
(一) 藥品配製 39
(二) RBL-2H3細胞之抗體、抗原及藥物處理 42
(三) Total cell lysate製備 42
(四) 蛋白質定量 42
(五) SDS-PAGE電泳分析 43
(六) 免疫轉漬 43
(七) 顯影拍攝 44
九、甘藍95%乙醇萃取物對IgE致敏及DNP-HSA抗原刺激RBL-2H3細胞之IL-4、IL-10及TNF-α含量測定 44
(一) 藥品配製 44
(二) RBL-2H3細胞之抗體、抗原及藥物處理 45
(三) 細胞激素含量測定 46
十、統計分析 46
陸、結果與討論 48
一、甘藍之水分含量及其萃取率 48
二、甘藍95%乙醇萃取物對RBL-2H3細胞之存活率 48
三、甘藍95%乙醇萃取物對IgE致敏及DNP-HSA抗原刺激RBL-2H3細胞β-hexosaminidase釋放之影響 48
四、甘藍95%乙醇萃取物對IgE致敏及DNP-HSA抗原刺激RBL-2H3細胞訊息傳導蛋白影響 51
(一) 磷酸化Lyn蛋白質表現 51
(二) 磷酸化Syk蛋白質表現 53
(三) 磷酸化LAT蛋白質表現 53
(四) 磷酸化Akt蛋白質表現 56
(五) 磷酸化MAPK家族蛋白質表現 56
(六) 磷酸化IP3R蛋白質表現 59
五、甘藍95%乙醇萃取物對IgE致敏及DNP-HSA抗原刺激RBL-2H3細胞質鈣離子濃度之影響 59
六、甘藍95%乙醇萃取物對未經致敏RBL-2H3細胞鈣離子調控之影響 61
七、甘藍95%乙醇萃取物對IgE致敏及DNP-HSA抗原刺激RBL-2H3細胞之發炎因子影響 64
(一) COX-2蛋白質表現 64
(二) TNF-α、IL-4及IL-10生成 64
柒、結論 68
捌、參考文獻 71

王仕賢與謝明憲。(1995)。甘藍。台灣農家要覽農作篇 (三), 2(5), 363-366。
Alvarez‐Errico, D., Lessmann, E., & Rivera, J. (2009). Adapters in the organization of mast cell signaling. Immunological reviews, 232(1), 195-217.
Arock, M., Zuany‐Amorim, C., Singer, M., Benhamou, M., & Pretolani, M. (1996). Interleukin‐10 inhibits cytokine generation from mast cells. European journal of immunology, 26(1), 166-170.
Asadujjaman, M., Hossain, M., Khan, M., Anisuzzaman, A., Ahmed, M., & Islam, A. (2011). Antihyperglycemic and glycogenesis effects of different fractions of brassica oleracea in Alloxan induced diabetic rats. International Journal of Pharmaceutical Sciences and Research, 2(6), 1436.
Askari, V. R., Rezaee, S. A., Abnous, K., Iranshahi, M., & Boskabady, M. H. (2016). The influence of hydro-ethanolic extract of Portulaca oleracea L. on Th1/Th2 balance in isolated human lymphocytes. Journal of ethnopharmacology, 194, 1112-1121.
Assad, T., Khan, R. A., & Feroz, Z. (2014). Evaluation of hypoglycemic and hypolipidemic activity of methanol extract of Brassica oleracea. Chinese journal of natural medicines, 12(9), 648-653.
Avato, P., & Argentieri, M. (2015). Brassicaceae: a rich source of health improving phytochemicals. Phytochemistry reviews, 14(6), 1019-1033.
Ayers, J. F. (2000). The use of alternative therapies in the support of breastfeeding. Journal of Human Lactation, 16(1), 52-56.
Bateman, E. D., Boulet, L., Cru, A., Fitzgerald, M., Haahtela, T., Levy, M., . . . Pedersen, S. (2010). Global strategy for asthma management and prevention. GINA executive summary, 2008, 31.
Beavitt, S.-J. E., Harder, K. W., Kemp, J. M., Jones, J., Quilici, C., Casagranda, F., . . . Sly, P. D. (2005). Lyn-deficient mice develop severe, persistent asthma: Lyn is a critical negative regulator of Th2 immunity. The Journal of Immunology, 175(3), 1867-1875.
Becker, Y. (2006). Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy—a review. Virus genes, 33(2), 235-252.
Bloemen, K., Verstraelen, S., Van Den Heuvel, R., Witters, H., Nelissen, I., & Schoeters, G. (2007). The allergic cascade: review of the most important molecules in the asthmatic lung. Immunology letters, 113(1), 6-18.
Boivin, D., Lamy, S., Lord-Dufour, S., Jackson, J., Beaulieu, E., Côté, M., . . . Béliveau, R. (2009). Antiproliferative and antioxidant activities of common vegetables: A comparative study. Food chemistry, 112(2), 374-380.
Brightling, C. E., Bradding, P., Symon, F. A., Holgate, S. T., Wardlaw, A. J., & Pavord, I. D. (2002). Mast-cell infiltration of airway smooth muscle in asthma. New England Journal of Medicine, 346(22), 1699-1705.
Burton, O. T., & Oettgen, H. C. (2011). Beyond immediate hypersensitivity: evolving roles for IgE antibodies in immune homeostasis and allergic diseases. Immunological reviews, 242(1), 128-143.
Cartea, M. E., Francisco, M., Soengas, P., & Velasco, P. (2011). Phenolic compounds in Brassica vegetables. Molecules, 16(1), 251-280.
Carvalho, C. A. d., Fernandes, K. M., Matta, S. L. P., Silva, M. B. d., Oliveira, L. L. d., & Fonseca, C. C. (2011). Evaluation of antiulcerogenic activity of aqueous extract of Brassica oleracea var. capitata (cabbage) on Wistar rat gastric ulceration. Arquivos de gastroenterologia, 48(4), 276-282.
Chaplin, D. D. (2010). Overview of the immune response. Journal of Allergy and Clinical Immunology, 125(2), S3-S23.
Chauhan, P. S., Singh, D., Dash, D., & Singh, R. (2018). Intranasal curcumin regulates chronic asthma in mice by modulating NF-ĸB activation and MAPK signaling. Phytomedicine, 51, 29-38.
Chiba, N., Masuda, A., Yoshikai, Y., & Matsuguchi, T. (2007). Ceramide inhibits LPS‐induced production of IL‐5, IL‐10, and IL‐13 from mast cells. Journal of cellular physiology, 213(1), 126-136.
Choi, J. H., Ryu, S. H., & Suh, P.-G. (2007). On/off-regulation of phospholipase C-gamma 1-mediated signal transduction.
Christensen, A. D., & Haase, C. (2012). Immunological mechanisms of contact hypersensitivity in mice. Apmis, 120(1), 1-27.
Chun, J., Lee, J., Ye, L., Exler, J., & Eitenmiller, R. R. (2006). Tocopherol and tocotrienol contents of raw and processed fruits and vegetables in the United States diet. Journal of Food Composition and Analysis, 19(2-3), 196-204.
Chung, F. (2001). Anti-inflammatory cytokines in asthma and allergy: interleukin-10, interleukin-12, interferon-γ. Mediators of inflammation, 10(2), 51-59.
Coopman, S., Degreef, H., & Dooms‐Goossens, A. (1989). Identification of cross‐reaction patterns in allergic contact dermatitis from topical corticosteroids. British Journal of Dermatology, 121(1), 27-34.
Cox, L., Larenas-Linnemann, D., Lockey, R. F., & Passalacqua, G. (2010). Speaking the same language: the World Allergy Organization subcutaneous immunotherapy systemic reaction grading system. Journal of Allergy and Clinical Immunology, 125(3), 569-574. e567.
Cruse, G., & Bradding, P. (2016). Mast cells in airway diseases and interstitial lung disease. European journal of pharmacology, 778, 125-138.
Duan, W., & Wong, W. F. (2006). Targeting mitogen-activated protein kinases for asthma. Current drug targets, 7(6), 691-698.
Enye, J., Chineke, H., Onubeze, D., & Nweke, I. (2013). Evaluation of the healing effects of aqueous extracts of Musa Paradisiaca (unripe plantain) and Brassica oleracea (cabbage) on peptic ulcer. IOSR J Dental Med Sci, 8, 40-46.
Evans, D. A., Hirsch, J. B., & Dushenkov, S. (2006). Phenolics, inflammation and nutrigenomics. Journal of the Science of Food and Agriculture, 86(15), 2503-2509.
Foer, D., Buchheit, K. M., Gargiulo, A. R., Lynch, D. M., Castells, M., & Wickner, P. G. (2016). Progestogen hypersensitivity in 24 cases: diagnosis, management, and proposed renaming and classification. The Journal of Allergy and Clinical Immunology: In Practice, 4(4), 723-729.
Fujita, H., Soyka, M. B., Akdis, M., & Akdis, C. A. (2012). Mechanisms of allergen-specific immunotherapy. Clinical and translational allergy, 2(1), 2.
Gaafar, A. A., Aly, H. F., Salama, Z. A., & Mohamed, N. Z. (2014). Hypoglycemic effects of white cabbage and red cabbage (Brassica oleracea) in STZ induced type 2 diabetes in rats. World Journal of Pharmaceutical Research, 3(4), 1583-1609.
Galli, S. J., & Tsai, M. (2010). Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. European journal of immunology, 40(7), 1843-1851.
Galli, S. J., & Tsai, M. (2012). IgE and mast cells in allergic disease. Nature medicine, 18(5), 693.
Galli, S. J., Tsai, M., & Piliponsky, A. M. (2008). The development of allergic inflammation. Nature, 454(7203), 445.
Gao, Y., Xu, B., Zhang, P., He, Y., Liang, X., Liu, J., & Li, J. (2017). TNF-α regulates mast cell functions by inhibiting cell degranulation. Cellular Physiology and Biochemistry, 44(2), 751-762.
Gasper, A. V., Traka, M., Bacon, J. R., Smith, J. A., Taylor, M. A., Hawkey, C. J., . . . Mithen, R. F. (2007). Consuming broccoli does not induce genes associated with xenobiotic metabolism and cell cycle control in human gastric mucosa. The Journal of nutrition, 137(7), 1718-1724.
Ghasemzadeh, A., Azarifar, M., Soroodi, O., & Jaafar, H. Z. (2012). Flavonoid compounds and their antioxidant activity in extract of some tropical plants. Journal of Medicinal Plants Research, 6(13), 2639-2643.
Gilfillan, A. M., & Beaven, M. A. (2011). Regulation of mast cell responses in health and disease. Critical reviews in immunology, 31(6), 475.
Gilfillan, A. M., & Tkaczyk, C. (2006). Integrated signalling pathways for mast-cell activation. Nature Reviews Immunology, 6(3), 218.
Gorinstein, S., Park, Y.-S., Heo, B.-G., Namiesnik, J., Leontowicz, H., Leontowicz, M., . . . Kang, S.-G. (2009). A comparative study of phenolic compounds and antioxidant and antiproliferative activities in frequently consumed raw vegetables. European Food Research and Technology, 228(6), 903-911.
Gould, H. J., & Sutton, B. J. (2008). IgE in allergy and asthma today. Nature Reviews Immunology, 8(3), 205.
Greineisen, W. E., Shimoda, L., Maaetoft‐Udsen, K., & Turner, H. (2012). Insulin‐containing lipogenic stimuli suppress mast cell degranulation potential and up‐regulate lipid body biogenesis and eicosanoid secretion in a PPARγ‐independent manner. Journal of leukocyte biology, 92(3), 653-665.
Groot Kormelink, T., Thio, M., Blokhuis, B., Nijkamp, F., & Redegeld, F. (2009). Atopic and non‐atopic allergic disorders: current insights into the possible involvement of free immunoglobulin light chains. Clinical & Experimental Allergy, 39(1), 33-42.
Gyllfors, P., Dahlén, S.-E., KumLin, M., Larsson, K., & Dahlén, B. (2006). Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate. Journal of Allergy and Clinical Immunology, 118(1), 78-83.
Hada, M., Nishi, K., Ishida, M., Onda, H., Nishimoto, S., & Sugahara, T. (2019). Inhibitory effect of aqueous extract of Cuminum cyminum L. seed on degranulation of RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. Cytotechnology, 1-11.
Hallab, N., Jacobs, J. J., & Black, J. (2000). Hypersensitivity to metallic biomaterials: a review of leukocyte migration inhibition assays. Biomaterials, 21(13), 1301-1314.
Han, E. H., Hwang, Y. P., Kim, H. G., Park, J. H., Choi, J. H., Im, J. H., . . . Choi, J. M. (2011). Ethyl acetate extract of Psidium guajava inhibits IgE-mediated allergic responses by blocking FcεRI signaling. Food and Chemical Toxicology, 49(1), 100-108.
Han, E. H., Park, J. H., Kim, J. Y., & Jeong, H. G. (2009). Houttuynia cordata water extract suppresses anaphylactic reaction and IgE-mediated allergic response by inhibiting multiple steps of FcεRI signaling in mast cells. Food and Chemical Toxicology, 47(7), 1659-1666.
Hawrylowicz, C. M. (2005). Regulatory T cells and IL-10 in allergic inflammation. Journal of Experimental Medicine, 202(11), 1459-1463.
Haytowitz, D. B., & Bhagwat, S. (2010). USDA database for the oxygen radical absorbance capacity (ORAC) of selected foods, Release 2. US Department of Agriculture, 10-48.
He, S.-h., Zhang, H.-y., Zeng, X.-n., Chen, D., & Yang, P.-c. (2013). Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis. Acta Pharmacologica Sinica, 34(10), 1270.
Heaton, T., Rowe, J., Turner, S., Aalberse, R., De Klerk, N., Suriyaarachchi, D., . . . Yerkovich, S. (2005). An immunoepidemiological approach to asthma: identification of in-vitro T cell response patterns associated with different wheezing phenotypes in children. The Lancet, 365(9454), 142-149.
Hirono, H., Morimitsu, Y., Kato, A., & Higashio, H. (2011). Glucosinolate profiles in cabbage (Brassica oleracea var. capitata) cultivars and their effect on the induction of a phase II detoxification enzyme. Journal of the Japanese Society for Horticultural Science, 80(4), 499-505.
Holgate, S. T. (1999). Genetic and environmental interaction in allergy and asthma. Journal of Allergy and Clinical Immunology, 104(6), 1139-1146.
Holgate, S. T., & Polosa, R. (2008). Treatment strategies for allergy and asthma. Nature Reviews Immunology, 8(3), 218.
Honda, T., & Kabashima, K. (2015). Prostanoids in allergy. Allergology International, 64(1), 11-16.
Huang, L., Li, T., Zhou, H., Qiu, P., Wu, J., & Liu, L. (2015). Sinomenine potentiates degranulation of RBL-2H3 basophils via up-regulation of phospholipase A2 phosphorylation by Annexin A1 cleavage and ERK phosphorylation without influencing on calcium mobilization. International immunopharmacology, 28(2), 945-951.
Illi, S., von Mutius, E., Lau, S., Niggemann, B., Grüber, C., & Wahn, U. (2006). Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. The Lancet, 368(9537), 763-770.
Ishida, M., Nishi, K., Watanabe, H., & Sugahara, T. (2013). Inhibitory effect of aqueous spinach extract on degranulation of RBL-2H3 cells. Food chemistry, 136(2), 322-327.
Itoh, T., Ohguchi, K., Iinuma, M., Nozawa, Y., & Akao, Y. (2008a). Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation. Bioorganic & medicinal chemistry, 16(8), 4500-4508.
Itoh, T., Ohguchi, K., Iinuma, M., Nozawa, Y., & Akao, Y. (2008b). Inhibitory effects of polymethoxy flavones isolated from Citrus reticulate on degranulation in rat basophilic leukemia RBL-2H3: Enhanced inhibition by their combination. Bioorganic & medicinal chemistry, 16(16), 7592-7598.
Jahangir, M., Kim, H. K., Choi, Y. H., & Verpoorte, R. (2009). Health‐affecting compounds in Brassicaceae. Comprehensive Reviews in Food Science and Food Safety, 8(2), 31-43.
Janeway, C. A. (2001). How the immune system works to protect the host from infection: a personal view. Proceedings of the National Academy of Sciences, 98(13), 7461-7468.
Jeong, H.-J., Hong, S.-H., Lee, D.-J., Park, J.-H., Kim, K.-S., & Kim, H.-M. (2002). Role of Ca2+ on TNF-α and IL-6 secretion from RBL-2H3 mast cells. Cellular signalling, 14(7), 633-639.
Jian, J., Konopka, J., & Liu, C. (2013). Insights into the role of progranulin in immunity, infection, and inflammation. Journal of leukocyte biology, 93(2), 199-208.
Jutel, M., Agache, I., Bonini, S., Burks, A. W., Calderon, M., Canonica, W., . . . O'Hehir, R. (2015). International consensus on allergy immunotherapy. Journal of Allergy and Clinical Immunology, 136(3), 556-568.
Jutel, M., & Akdis, C. (2011). Immunological mechanisms of allergen‐specific immunotherapy. Allergy, 66(6), 725-732.
Jutel, M., Akdis, M., & Akdis, C. (2009). Histamine, histamine receptors and their role in immune pathology. Clinical & Experimental Allergy, 39(12), 1786-1800.
Kalesnikoff, J., & Galli, S. J. (2008). New developments in mast cell biology. Nature immunology, 9(11), 1215.
Kay, A. B. (2001). Allergy and allergic diseases. New England Journal of Medicine, 344(1), 30-37.
Khan, R. A., Asad, T., Feroz, Z., & Ahmed, M. (2015). In vivo examination of the anticoagulant effect of the Brassica oleracea methanol extract. Arch Biol Sci, 67, 631-638.
Kim, D. O., Padilla‐Zakour, O., & Griffiths, P. (2004). Flavonoids and antioxidant capacity of various cabbage genotypes at juvenile stage. Journal of Food Science, 69(9), C685-C689.
Kitahata, Y., Nunomura, S., Terui, T., & Ra, C. (2010). Prolonged culture of mast cells with high-glucose medium enhances the FcεRI-mediated degranulation response and leukotriene C4 production. International archives of allergy and immunology, 152(Suppl. 1), 22-31.
Ko, Y.-J., Kim, H.-H., Kim, E.-J., Katakura, Y., Lee, W.-S., Kim, G.-S., & Ryu, C.-H. (2013). Piceatannol inhibits mast cell-mediated allergic inflammation. International journal of molecular medicine, 31(4), 951-958.
Kopeć, A., Panaszek, B., & Fal, A. M. (2006). Intracellular signaling pathways in IgE-dependent mast cell activation. Archivum immunologiae et therapiae experimentalis, 54(6), 393-401.
Koyasu, S. (2003). The role of PI3K in immune cells. Nature immunology, 4(4), 313.
Kreuzer, M., O’Sullivan, C., Pravda, M., & Guilbault, G. (2001). Development of an immunosensor for the determination of allergy antibody (IgE) in blood samples. Analytica chimica acta, 442(1), 45-53.
Lambrecht, B. N., & Hammad, H. (2017). The immunology of the allergy epidemic and the hygiene hypothesis. Nature immunology, 18(10), 1076.
Liang, H.-E., Reinhardt, R. L., Bando, J. K., Sullivan, B. M., Ho, I.-C., & Locksley, R. M. (2012). Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nature immunology, 13(1), 58.
Lindquist, J. A., Simeoni, L., & Schraven, B. (2003). Transmembrane adapters: attractants for cytoplasmic effectors. Immunological reviews, 191(1), 165-182.
Liu, R., Che, D., Zhao, T., Pundir, P., Cao, J., Lv, Y., . . . Wang, N. (2017). MRGPRX2 is essential for sinomenine hydrochloride induced anaphylactoid reactions. Biochemical pharmacology, 146, 214-223.
Liu, R., Zhao, T., Che, D., Cao, J., Wang, J., Lv, Y., . . . Wang, X. (2018). The anti-anaphylactoid effects of hydroxysafflor yellow A on the suppression of mast cell Ca2+ influx and degranulation. Phytomedicine, 48, 43-50.
Ma, Y., Zhang, J.-X., Liu, Y.-N., Ge, A., Gu, H., Zha, W.-J., . . . Huang, M. (2016). Caffeic acid phenethyl ester alleviates asthma by regulating the airway microenvironment via the ROS-responsive MAPK/Akt pathway. Free Radical Biology and Medicine, 101, 163-175.
Marshall, J. S. (2004). Mast-cell responses to pathogens. Nature Reviews Immunology, 4(10), 787.
Marshall, J. S., Leal-Berumen, I., Nielsen, L., Glibetic, M., & Jordana, M. (1996). Interleukin (IL)-10 inhibits long-term IL-6 production but not preformed mediator release from rat peritoneal mast cells. The Journal of clinical investigation, 97(4), 1122-1128.
Martínez, S., Olmos, I., Carballo, J., & Franco, I. (2010). Quality parameters of Brassica spp. grown in northwest Spain. International journal of food science & technology, 45(4), 776-783.
Masuda, E. S., & Schmitz, J. (2008). Syk inhibitors as treatment for allergic rhinitis. Pulmonary pharmacology & therapeutics, 21(3), 461-467.
Mattila, P., & Hellström, J. (2007). Phenolic acids in potatoes, vegetables, and some of their products. Journal of Food Composition and Analysis, 20(3-4), 152-160.
Matura, M., Goossens, A., & Matura, M. (2000). Contact allergy to corticosteroids. Allergy, 55(8), 698-704.
McLeod, J. J., Baker, B., & Ryan, J. J. (2015). Mast cell production and response to IL-4 and IL-13. Cytokine, 75(1), 57-61.
Metcalfe, D. D., Peavy, R. D., & Gilfillan, A. M. (2009). Mechanisms of mast cell signaling in anaphylaxis. Journal of Allergy and Clinical Immunology, 124(4), 639-646.
Miean, K. H., & Mohamed, S. (2001). Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. Journal of agricultural and food chemistry, 49(6), 3106-3112.
Mäkelä, M., Kanehiro, A., Borish, L., Dakhama, A., Loader, J., Joetham, A., . . . Gelfand, E. (2000). IL-10 is necessary for the expression of airway hyperresponsiveness but not pulmonary inflammation after allergic sensitization. Proceedings of the National Academy of Sciences, 97(11), 6007-6012.
Morishita, Y., Saito, E., Takemura, E., Fujikawa, R., Yamamoto, R., Kuroyanagi, M., . . . Muto, N. (2015). Flavonoid glucuronides isolated from spinach inhibit IgE mediated degranulation in basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice. Integr Mol Med, 2, 99-105.
Nagai, H., Abe, T., Yamaguchi, I., Mito, K., Tsunematsu, M., Kimata, M., & Inagaki, N. (2000). Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in mice. Journal of Allergy and Clinical Immunology, 106(1), S91-S98.
Nakano, T., Andoh, T., Lee, J.-B., & Kuraishi, Y. (2008). Different dorsal horn neurons responding to histamine and allergic itch stimuli. Neuroreport, 19(7), 723-726.
Namork, E., Johansen, B. V., & Løvik, M. (2006). Detection of allergens adsorbed to ambient air particles collected in four European cities. Toxicology letters, 165(1), 71-78.
Ninomiya, M., Itoh, T., Ishikawa, S., Saiki, M., Narumiya, K., Yasuda, M., . . . Koketsu, M. (2010). Phenolic constituents isolated from Fragaria ananassa Duch. inhibit antigen-stimulated degranulation through direct inhibition of spleen tyrosine kinase activation. Bioorganic & medicinal chemistry, 18(16), 5932-5937.
Nishizumi, H., & Yamamoto, T. (1997). Impaired tyrosine phosphorylation and Ca2+ mobilization, but not degranulation, in lyn-deficient bone marrow-derived mast cells. The Journal of Immunology, 158(5), 2350-2355.
Odom, S., Gomez, G., Kovarova, M., Furumoto, Y., Ryan, J. J., Wright, H. V., . . . Rivera, J. (2004). Negative regulation of immunoglobulin E–dependent allergic responses by Lyn kinase. Journal of Experimental Medicine, 199(11), 1491-1502.
Oguwike, F., Offor, C., Nwadighoha, A., & Ebede, S. (2014). Evaluation of efficacy of cabbage juice (Brassica oleracea Linne) as potential antiulcer aggent and its effect on the haemostatic mechanism of male albino wistar rats. J Dental Med Sci, 13, 92-97.
Okkenhaug, K., & Vanhaesebroeck, B. (2003). PI3K in lymphocyte development, differentiation and activation. Nature Reviews Immunology, 3(4), 317.
Overman, E. L., Rivier, J. E., & Moeser, A. J. (2012). CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α. PloS one, 7(6), e39935.
Parravicini, V., Gadina, M., Kovarova, M., Odom, S., Gonzalez-Espinosa, C., Furumoto, Y., . . . Rivera, J. (2002). Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nature immunology, 3(8), 741.
Podse˛ dek, A., Sosnowska, D., Redzynia, M., & Anders, B. (2006). Antioxidant capacity and content of Brassica oleracea dietary antioxidants. International journal of food science & technology, 41, 49-58.
Radonjic-Hoesli, S., Hofmeier, K. S., Micaletto, S., Schmid-Grendelmeier, P., Bircher, A., & Simon, D. (2018). Urticaria and angioedema: an update on classification and pathogenesis. Clinical reviews in allergy & immunology, 54(1), 88-101.
Rhoades, R., & Pflanzer, R. (2002). Human Physiology 4th. Thomson Learning.
Rivera, J., & Gilfillan, A. M. (2006). Molecular regulation of mast cell activation. Journal of Allergy and Clinical Immunology, 117(6), 1214-1225.
Rokayya, S., Li, C.-J., Zhao, Y., Li, Y., & Sun, C.-H. (2013). Cabbage (Brassica oleracea L. var. capitata) phytochemicals with antioxidant and anti-inflammatory potential. Asian Pacific Journal of Cancer Prevention, 14(11), 6657-6662.
Romagnani, S. (2004). Immunologic influences on allergy and the TH1/TH2 balance. Journal of Allergy and Clinical Immunology, 113(3), 395-400.
Royer, B., Varadaradjalou, S., Saas, P., Guillosson, J., Kantelip, J., & Arock, M. (2001). Inhibition of IgE‐induced activation of human mast cells by IL‐10. Clinical & Experimental Allergy, 31(5), 694-704.
Saitoh, S.-i., Odom, S., Gomez, G., Sommers, C. L., Young, H. A., Rivera, J., & Samelson, L. E. (2003). The four distal tyrosines are required for LAT-dependent signaling in FcεRI-mediated mast cell activation. Journal of Experimental Medicine, 198(5), 831-843.
Šamec, D., Pavlović, I., & Salopek-Sondi, B. (2017). White cabbage (Brassica oleracea var. capitata f. alba): botanical, phytochemical and pharmacological overview. Phytochemistry reviews, 16(1), 117-135.
Sanderson, M. P., Lau, C. W., Schnapp, A., & Chow, C.-W. (2009). Syk: a novel target for treatment of inflammation in lung disease. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy), 8(2), 87-95.
Sanderson, M. P., Wex, E., Kono, T., Uto, K., & Schnapp, A. (2010). Syk and Lyn mediate distinct Syk phosphorylation events in FcɛRI-signal transduction: implications for regulation of IgE-mediated degranulation. Molecular immunology, 48(1-3), 171-178.
Santiago, F., Gonçalo, M., Vieira, R., Coelho, S., & Figueiredo, A. (2010). Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS). Contact Dermatitis, 62(1), 47-53.
Sato, Y., Akiyama, H., Suganuma, H., Watanabe, T., Nagaoka, M. H., Inakuma, T., . . . Maitani, T. (2004). The feeding of β-carotene down-regulates serum IgE levels and inhibits the type I allergic response in mice. Biological and Pharmaceutical Bulletin, 27(7), 978-984.
Schnuch, A., Westphal, G., Mössner, R., Uter, W., & Reich, K. (2011). Genetic factors in contact allergy—review and future goals. Contact Dermatitis, 64(1), 2-23.
Serra‐Pages, M., Olivera, A., Torres, R., Picado, C., Mora, F., & Rivera, J. (2012). E‐prostanoid 2 receptors dampen mast cell degranulation via cAMP/PKA‐mediated suppression of IgE‐dependent signaling. Journal of leukocyte biology, 92(6), 1155-1165.
Shamji, M., & Durham, S. (2011). Mechanisms of immunotherapy to aeroallergens. Clinical & Experimental Allergy, 41(9), 1235-1246.
Shibata, T., Nakashima, F., Honda, K., Lu, Y.-J., Kondo, T., Ushida, Y., . . . Tanaka, H. (2014). Toll-like receptors as a target of food-derived anti-inflammatory compounds. Journal of Biological Chemistry, 289(47), 32757-32772.
Shimada, J., Yano, H., & Mizumachi, K. (2005). Trends in food allergy research (1349-3663). Retrieved from
Sibilano, R., Frossi, B., & Pucillo, C. E. (2014). Mast cell activation: a complex interplay of positive and negative signaling pathways. European journal of immunology, 44(9), 2558-2566.
Silveira, A. E. S., Mazucato, V. M., Jamur, M. C., & Oliver, C. (2011). Lipid rafts in mast cell biology. Journal of lipids, 2011, 752906-752906.
Singh, J., Upadhyay, A., Prasad, K., Bahadur, A., & Rai, M. (2007). Variability of carotenes, vitamin C, E and phenolics in Brassica vegetables. Journal of Food Composition and Analysis, 20(2), 106-112.
Siraganian, R. P., de Castro, R. O., Barbu, E. A., & Zhang, J. (2010). Mast cell signaling: the role of protein tyrosine kinase Syk, its activation and screening methods for new pathway participants. FEBS letters, 584(24), 4933-4940.
Sivakumar, G., Aliboni, A., & Bacchetta, L. (2007). HPLC screening of anti-cancer sulforaphane from important European Brassica species. Food chemistry, 104(4), 1761-1764.
Sompayrac, L. M. (2019). How the immune system works: Wiley-Blackwell.
Song, W., Zhang, Y., Wang, J., Ma, T., Hao, L., & Wang, K. (2018). Antagonism of cysteinyl leukotriene receptor 1 (cysLTR1) by montelukast suppresses cell senescence of chondrocytes. Cytokine, 103, 83-89.
Sreeramulu, D., & Raghunath, M. (2010). Antioxidant activity and phenolic content of roots, tubers and vegetables commonly consumed in India. Food Research International, 43(4), 1017-1020.
Stone, K. D., Prussin, C., & Metcalfe, D. D. (2010). IgE, mast cells, basophils, and eosinophils. Journal of Allergy and Clinical Immunology, 125(2), S73-S80.
Suido, H., Tanaka, T., Tabei, T., Takeuchi, A., Okita, M., Kishimoto, T., . . . Higashino, K. (2002). A mixed green vegetable and fruit beverage decreased the serum level of low-density lipoprotein cholesterol in hypercholesterolemic patients. Journal of agricultural and food chemistry, 50(11), 3346-3350.
Suto, A., Nakajima, H., Kagami, S.-i., Suzuki, K., Saito, Y., & Iwamoto, I. (2001). Role of CD4+ CD25+ regulatory T cells in T helper 2 cell-mediated allergic inflammation in the airways. American journal of respiratory and critical care medicine, 164(4), 680-687.
Takhar, P., Corrigan, C. J., Smurthwaite, L., O'Connor, B. J., Durham, S. R., Lee, T. H., & Gould, H. J. (2007). Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic patients with asthma. Journal of Allergy and Clinical Immunology, 119(1), 213-218.
Talaat, R. M., Mohamed, S. F., Bassyouni, I. H., & Raouf, A. A. (2015). Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine, 72(2), 146-153.
Tan, J. W., Israf, D. A., Hashim, N. F. M., Cheah, Y. K., Harith, H. H., Shaari, K., & Tham, C. L. (2017). LAT is essential for the mast cell stabilising effect of tHGA in IgE-mediated mast cell activation. Biochemical pharmacology, 144, 132-148.
Tournoy, K., Kips, J., & Pauwels, R. (2000). Endogenous interleukin-10 suppresses allergen-induced airway inflammation and nonspecific airway responsiveness. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology, 30(6), 775-783.
Usmani, O. S., Ito, K., Maneechotesuwan, K., Ito, M., Johnson, M., Barnes, P. J., & Adcock, I. M. (2005). Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy. American journal of respiratory and critical care medicine, 172(6), 704-712.
Uzzaman, A., & Cho, S. H. (2012). Classification of hypersensitivity reactions. Paper presented at the Allergy & Asthma Proceedings.
Velasco, P., Francisco, M., Moreno, D. A., Ferreres, F., García‐Viguera, C., & Cartea, M. E. (2011). Phytochemical fingerprinting of vegetable Brassica oleracea and Brassica napus by simultaneous identification of glucosinolates and phenolics. Phytochemical Analysis, 22(2), 144-152.
Vo, T.-S., Kong, C.-S., & Kim, S.-K. (2011). Inhibitory effects of chitooligosaccharides on degranulation and cytokine generation in rat basophilic leukemia RBL-2H3 cells. Carbohydrate Polymers, 84(1), 649-655.
Wang, N., Liu, R., Liu, Y., Zhang, R., & He, L. (2016). Sinomenine potentiates P815 cell degranulation via upregulation of Ca2+ mobilization through the Lyn/PLCγ/IP3R pathway. International journal of immunopathology and pharmacology, 29(4), 676-683.
Wang, Y., Zhou, J., Fu, S., Wang, C., & Zhou, B. (2015). A study of association between oral lichen planus and immune balance of Th1/Th2 cells. Inflammation, 38(5), 1874-1879.
Waqar, M. A., & Mahmmod, Y. (2010). Anti-platelet, anti-hypercholesterolemic and anti-oxidant effects of ethanolic extracts of brassica oleracea in high fat diet provided rats. World Applied Sciences Journal, 8(1), 107-112.
Wechsler, M. E., Grasemann, H., Deykin, A., Silverman, E. K., Yandava, C. N., Israel, E., . . . Drazen, J. M. (2000). Exhaled nitric oxide in patients with asthma: association with NOS1 genotype. American journal of respiratory and critical care medicine, 162(6), 2043-2047.
Weichhart, T., & Säemann, M. (2008). The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications. Annals of the rheumatic diseases, 67(Suppl 3), iii70-iii74.
Wernersson, S., & Pejler, G. (2014). Mast cell secretory granules: armed for battle. Nature Reviews Immunology, 14(7), 478.
Westereng, B., Yousif, O., Michaelsen, T. E., Knutsen, S. H., & Samuelsen, A. B. (2006). Pectin isolated from white cabbage–structure and complement‐fixing activity. Molecular nutrition & food research, 50(8), 746-755.
Williams, C. M., & Galli, S. J. (2000). Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. Journal of Experimental Medicine, 192(3), 455-462.
Williams, C. M., Rahman, S., Hubeau, C., & Ma, H.-L. (2012). Cytokine pathways in allergic disease. Toxicologic pathology, 40(2), 205-215.
Xiao, W., Nishimoto, H., Hong, H., Kitaura, J., Nunomura, S., Maeda-Yamamoto, M., . . . Kawakami, T. (2005). Positive and negative regulation of mast cell activation by Lyn via the FcεRI. The Journal of Immunology, 175(10), 6885-6892.
Xystrakis, E., Kusumakar, S., Boswell, S., Peek, E., Urry, Z., Richards, D. F., . . . Loke, T.-K. (2006). Reversing the defective induction of IL-10–secreting regulatory T cells in glucocorticoid-resistant asthma patients. The Journal of clinical investigation, 116(1), 146-155.
Yang, X., Wang, S., Fan, Y., & Han, X. (2000). IL‐10 deficiency prevents IL‐5 overproduction and eosinophilic inflammation in a murine model of asthma‐like reaction. European journal of immunology, 30(2), 382-391.
Yasunaga, S., Nishi, K., Nishimoto, S., & Sugahara, T. (2015). Methoxychlor enhances degranulation of murine mast cells by regulating FcϵRI-mediated signal transduction. Journal of immunotoxicology, 12(3), 283-289.
Yoo, J.-M., Kim, N. Y., Seo, J. M., Kim, S.-J., Lee, S. Y., Kim, S. K., . . . Kim, M. R. (2014). Inhibitory effects of mulberry fruit extract in combination with naringinase on the allergic response in IgE-activated RBL-2H3 cells. International journal of molecular medicine, 33(2), 469-477.
Zuercher, A., Holvoet, S., Weiss, M., & Mercenier, A. (2010). Polyphenol‐enriched apple extract attenuates food allergy in mice. Clinical & Experimental Allergy, 40(6), 942-950.