柑橘類黃酮化合物抑制 PMA/Ionomycin 誘導小鼠 EL-4 細胞 IL-5 表現之影響

楊濰菱

doi:10.6845/NCHU.2015.00686

3.237.97.64，Hello！

Close
Search Quick Search Advanced Search Publication Search	Personal Service Member Login Searching History Use Bonus Card SYMSKAN
Browse Browse by University of Graduate Thesis Browse by Pinyin of Graduate Thesis Browse by Conference Proceedings Topic Browse by Conference Proceedings Publisher Browse by Pinyin of Conference Proceedings Browse by eBook Category Browse by eBook Topic Browse by eBook Publisher
Customer Services Authorize Airiti Recommend a Journal

Search Symbol (Half-width)	Description of Search Symbols
Space	"AND" indicates the intertwining of key terms used in a search
Double Quotation Marks ("") ( " " )	Double quotation marks indicate the beginning and end of a phrase, and the search will only include terms that appear in the same order of those within the quotations. Example: "image process" ： " image process "
?	Indicates a variable letter. Entering two ? will indicate two variable letters, and so on. Example: "Appl?", search results will yield apple, apply… e , appl y … ( (often used to English word searches) )
*	Indicates an unlimited number of variable letters to follow, from 1~n. Example: Enter "appl*", search results will yield apple, apples, apply, applied, application…(often used in English word searches) e , appl es , appl y , appl ied , appl ication … ( (often used to English word searches) )
AND、OR、NOT	Boolean logic combinations of key words is a skill used to expand or refine search parameters. (1) AND (1) AND: Refines search parameters (2) OR (2) OR: Expands search parameters (3) NOT: Excludes irrelevant parameters

DOI stands for Digital Object Identifier （ D igital O bject I dentifier ） ,
and is the unique identifier for objects on the internet. It can be used to create persistent link and to cite articles.

Using DOI as a persistent link

To create a persistent link, add「http://dx.doi.org/」「 http://dx.doi.org/ 」 before a DOI.
For instance, if the DOI of an article is 10.5297/ser.1201.002 , you can link persistently to the article by entering the following link in your browser: http://dx.doi.org/ 10.5297/ser.1201.002 。
The DOI link will always direct you to the most updated article page no matter how the publisher changes the document's position, avoiding errors when engaging in important research.

Cite a document with DOI

When citing references, you should also cite the DOI if the article has one. If your citation guideline does not include DOIs, you may cite the DOI link.

DOIs allow accurate citations, improve academic contents connections, and allow users to gain better experience across different platforms. Currently, there are more than 70 million DOIs registered for academic contents. If you want to understand more about DOI, please visit airiti DOI Registration （ doi.airiti.com ）。

Data Source

College of Agriculture and Natural Resourses > Department of Food Science and Biotechnology
Bio-Agriculture > Biological Science

Bibliography Management Tool

Related Links

Report an Issue

Purchase Single Articles

Download PDF

柑橘類黃酮化合物抑制 PMA/Ionomycin 誘導小鼠 EL-4 細胞 IL-5 表現之影響

Inhibitory effects of citrus flavonoids on the expression of IL-5 in PMA/Ionomycin-induced EL-4 cells

楊濰菱 , Masters　　Advisor：顏國欽　　

繁體中文 DOI： 10.6845/NCHU.2015.00686

過敏；介白素-5 ；柑橘類黃酮化合物； EL-4 細胞株； ROS ； allergy ； IL-5 ； citrus flavonoids ； EL-4 cell ； ROS

Abstract │ Reference (190) │ Altmetrics

Abstract 〈TOP〉

適應性免疫反應通常為正常有益的調節作用，但此反應若過度活化則會造成過敏現象。過敏反應的發生是外來過敏原刺激並活化體內免疫系統，使得輔助型 T 淋巴球傾向第二類輔助型 T 細胞 (type 2 helper T-cells，Th2) 之分化，造成過敏相關抗體與細胞激素 (cytokine) 產生。介白素-5 (interleukin 5, IL-5) 是 Th2 細胞主要分泌的細胞激素之一，在許多免疫反應中擔任重要的調控角色，並與嗜酸性球 (eosinophils) 的生長分化具密切關係，因而與氣喘、異位性皮膚炎、嗜酸性球增多症等免疫疾病呈正相關。柑橘類黃酮化合物具有廣泛的生物活性，包含抗菌、抗氧化與抗發炎等生理功效，具有免疫調節改善過敏之潛力。本研究目的為探討柑橘類黃酮化合物抑制發炎介質 phorbol 12-myristate 13-acetate (PMA) 與 Ionomycin 對小鼠淋巴瘤 (EL-4) 細胞株誘導 IL-5 分泌及 ROS (reactive oxygen species) 生成之機轉。
首先以 PMA/Ionomycin 誘導 EL-4 細胞株 IL-5 與胞內 ROS 的生成。並介入五種柑橘類黃酮化合物，分別為川陳皮素 (nobiletin)、橘皮素 (tangeretin)、5-去甲基川陳皮素 (5-demethyl nobiletin, 5-DN)、橙皮苷 (hesperetin) 及梔子素 A (gardenin A)，評估此五種柑橘類黃酮化合物對於 PMA/Ionomycin 誘導 IL-5 分泌與胞內 ROS  生成之抑制效應。實驗結果以橙皮苷與梔子素 A 之抑制效果最佳，並證實橙皮苷與梔子素 A 可透過抑制細胞核內 Th2 相關轉錄因子 nuclear factor of activated T cells (NFAT) 及activator protein 1 (AP-1) 路徑之表現，而具有減緩 EL-4 細胞中 Th2 過敏反應之潛力。更進一步探討橙皮苷與梔子素 A 對於抗氧化與抗發炎相關之轉錄因子 nuclear factor-erythroid 2 related factor 2 (Nrf2) 與 peroxisome proliferators activated receptor γ (PPARγ) 之影響。結果顯示橙皮苷可以透過提升 phosphoinositide 3-kinase/protein kinase B (PI3K/Akt)、extracellular signal-regulated kinase (ERK) 及 c-Jun N-terminal kinase II JNK) 蛋白磷酸化，進而活化 Nrf2 與 heme oxygenase 1 (HO-1) 表現，並具有減少 PMA/Ionomycin 誘導之核內 NFAT 蛋白表現及 IL-5 釋放之功效。此外，梔子素 A 則可透過活化 PPARγ 與 HO-1，減少 PMA/ Ionomycin 誘導之核內 AP-1 蛋白表現與 IL-5 生成。
綜合上述結果，此兩種柑橘類黃酮化合物 (橙皮苷與梔子素 A) 可透過活化 EL-4 細胞之 Nrf2 或 PPARγ，並降低 PMA/Ionomycin 誘導 NFAT 蛋白之表現，進而達到抑制 IL-5 分泌及 ROS 產生。因此，柑橘類黃酮化合物可能具改善 Th2 相關免疫失衡等過敏現象之潛力。

Parallel Abstract 〈TOP〉

Adaptive immune response is usually an ordinary and beneficial regulating function, however, it should be balanced between type 1 helper T-cells (Th1) and Th2 activity. The inability to respond adequately with a Th1 response may result in chronic infection an  overactive Th2 immune response may contribute to  allergies. Th1/Th2 imbalance towards Th2 response will lead to related Th2 cytokines and antibodies secretion, interleukin 5 (IL-5). IL-5 is a key cytokine produced by Th2 cells, involving in eosinophil growth and  differentiation in bone marrow. Dysregulated production of IL-5 by Th2 cells has been linked with eosinophilic inflammatory and allergic diseases.
Citrus flavonoids have been reported to possess a variety of beneficial qualities, including anti-viral, anti-inflammatory and anti-oxidant properties. Because of their capacity to inhibit inflammatory reactions, there is potential for citrus flavonoids to improve symptoms of allergies.The aim of this study was to investigate effects of citrus flavonoids on phorbol 12-myristate 13-acetate (PMA) plus ionomycin-induced IL-5 cytokine and reactive oxygen species (ROS)  production in Th2 cells, and the underlying mechanism.
To evaluate the anti-allergic activity of citrus flavonoids, including nobiletin, tangeretin, 5-demethyl nobiletin (5-DN), hesperetin and gardenin A, the expressions of IL-5 and ROS by PMA/Ionomycin-induced EL-4 cells were determined. Results showed that  treatments with six selected citrus flavonoids  significantly inhibited the production of IL-5 and ROS, especially hesperidin and gardenin A, by blocking  the Th2-related nuclear transcription factors including  nuclear factor of activated T cells (NFAT) or activator  protein 1 (AP-1). We found that citrus flavonoids  inhibited NFAT, which might in turn downregulate Th2-allergic inflammatory responses; therefore, citrus flavonoids might suppress IL-5 and ROS expression by inhibiting NFAT activation. 
We further investigates the relationship between hesperetin as well as gardenin-A and nuclear transcription factors nuclear factor-erythroid 2 related factor 2 (Nrf2) and peroxisome proliferators activated receptor γ (PPARγ), because of their anti-inflammatory or anti-oxidative roles in the immune system. In this studies, we showed that activation of Nrf2 and HO-1 via increasing the phosphorylation of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) might play an important role in the hesperidin-induced inhibition of NFAT expression in EL-4 cells.Furthermore, gardenin A can activate PPARγ and HO-1 via downregulation of AP-1, hence decreasing the production of IL-5 and ROS by PMA and Ionomycin.
This study suggests that downregulation of NFAT via the activation of Nrf2 and PPARγ might contribute to the inhibitory effect of those citrus flavonoids (hesperidin and gardenin A) on mitogen-induced IL-5 and ROS production in EL-4 cells. Furthermore, citrus flavonoids (hesperidin and gardenin A) is potential to regulate immune homeostasis and anti-allergic properties.

Reference ( 190 ) 〈TOP〉

Abbas, A. K.; Murphy, K. M.; Sher, A., Functional diversity of helper T lymphocytes. Nature 1996, 383, 787-793.
連結：
Adams, M.; Reginato, M. J.; Shao, D.; Lazar, M. A.; Chatterjee, V. K., Transcriptional activation by peroxisome proliferator-activated receptor gamma is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J Biol Chem 1997, 272, 5128-5132.
連結：
Ahmad, S. F.; Zoheir, K. M.; Abdel-Hamied, H. E.; Ashour, A. E.; Bakheet, S. A.; Attia, S. M.; Abd-Allah, A. R., Amelioration of autoimmune arthritis by naringin through modulation of T regulatory cells and Th1/Th2 cytokines. Cell Immunol 2014, 287, 112-120.
連結：
Alam, J.; Cook, J. L., How many transcription factors does it take to turn on the heme oxygenase-1 gene? Am J Respir Cell Mol Biol 2007, 36, 166-174.
連結：
Alvarez-Maqueda, M.; El Bekay, R.; Alba, G.; Monteseirin, J.; Chacon, P.; Vega, A.; Martin-Nieto, J.; Bedoya, F. J.; Pintado, E.; Sobrino, F., 15-deoxy-delta 12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes. J Biol Chem 2004, 279, 21929-21937.
連結：

Altmetrics

〈TOP〉

E-mail ：

When an article is available to download, a notice will be sent to your mailbox address.

E-mail ：