探討酪胺酸激酶抑制劑對家塵螨誘發炎症之影響及機制

陳蘋如

18.208.126.232，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

Health & Medical Care > Medical Sciences
College of Medicine > Graduate Institute of Medicine

Bibliography Management Tool

Related Links

Report an Issue

Purchase Single Articles

Download PDF

探討酪胺酸激酶抑制劑對家塵螨誘發炎症之影響及機制

Tyrosine Kinase Inhibitors Alleviated House Dust Mite Allergen Der pII-induced Inflammation

陳蘋如 , Masters　　Advisor：柯俊良　　

繁體中文

氣喘；家塵螨表皮生長因子；酪胺酸酶抑制劑； asthma ； house dust mite ； epithelial growth factor receptor ； Tyrosine kinase inhibitor

Abstract │ Reference (151) │ Altmetrics

Abstract 〈TOP〉

家塵螨引發的氣喘是常見的炎症之一，其中Dermatophagoides pteronyssinus是造成氣喘的主要過敏原，會誘發特異性抗原CD4+ Th2產生免疫反應。過去研究發現呼吸道上皮細胞中活化的鐸受體(Toll-like receptor, TLR)外，表皮生長因子接受器 (Epidermal growth factor receptor, EGFR) 也是調控過敏性呼吸道疾病的重要因子之一。本實驗將探討酪胺酸激酶抑制劑 (Tyrosine Kinase Inhibitors, TKIs) 是否抑制家塵螨誘發的免疫反應及其機制，並釐清家塵螨對不同型態細胞種類及其微環境的致敏關係。首先，我們在人類周邊血液單核球細胞(HPBMC)預處理TKIs (Tarceva、AZD-9291) 並用Dermatophagoides pteronyssinus重組蛋白-Der pII刺激，以酵素結合免疫吸附分析 (ELISA) 來測定相關激素之變化，結果發現 TKIs 可以有效減IL-6和IL-8之分泌。其次，結果發現在人類肺上皮細胞(BEAS-2B) 中，以 ELISA、RT-PCR和Real-time PCR，TKIs皆可有效抑制 Der pII 所誘發的IL-6和 IL-8之表現，以西方墨點法分析EGFR以及AMPK之活化，則觀察到Tarceva可抑制p-EGFR之活化以及其下游相關蛋白p-AKT，而AZD-9291雖無法抑制p-EGFR之活化，但仍可有效抑制其下游相關蛋白p-STAT3和p-AKT，而TKIs抑制上皮細胞發炎之機轉並非透過AMPK之活化；在核質分離法中發現AZD-9291主要是抑制NF-κB之進核作用。另外，結果發現在大鼠肺泡巨噬細胞 (NR8383) 中，以 Griess Reagent System 測定一氧化氮 (NO) 之產生，則 AZD-9291 可有效抑制 Der pII 所誘發的 NO 之產生，但無法抑制 iNOS 基因之表現。最後，結果發現在單核球和巨噬細胞中，以RT-PCR觀察巨噬細胞相關指標CD14和 CD36，結果發現AZD-9291可抑制Der pII所誘發CD14和CD36之基因表現，在西方墨點法中發現AZD-9291可促使p-AMPK之表現，但無法抑制 Der pII所誘發之capase-1。綜合以上實驗結果，AZD-9291可透過抑制p-AKT / p-STAT3訊號路徑、NF-κB之進核作用及AMPK活化來減緩 Der pII 所造成之IL-6、IL-8之分泌。因此AZD-9291可發展為減緩家塵蟎 Der pII所引起發炎反應的臨床治療藥物。

Parallel Abstract 〈TOP〉

House dust mites (HDM；Dermatophagoides pteronyssinus.) is one of the common sources of airborne allergens worldwide. It activates specific CD4+ Th2 cells to orchestrate the HDM-induced allergic response. Previous study demonstrated that both Toll-like receptor (TLR) and  epithelial growth factor receptor (EGFR) signaling regulated the key features of allergic airway disease in airway epithelial cells. The aim of study investigated whether tyrosine kinase inhibitors affect Derp II -induced inflammation in various cell types and their microenvironment. To determine related cytokines stimulated by recombinant protein Der pII in HPBMC, we demonstrated that pre-treatment of TKIs such as Tarceva and AZD-9291 effectively inhibits the production of IL-6 and IL-8 by ELISA. Second, Tarceva and AZD-9291 inhibited the Der pII-induced expression of IL-6 and IL-8 in human lung epithelial cells (BEAS-2B) by ELISA, RT-PCR and Real-time PCR. On Western blot, Tarceva decreased both phosphorylated EGFR and its downstream p-AKT, whereas AZD-9291 only decreased its downstream p-STAT3 and p-AKT, indication mechanism of TKIs inhibition wsa not associated with AMPK activation in human lung epithelial cells. Moreover, AZD-9291 inhibited NF-κB transloction to nucleus. Third, AZD-9291 effectively decreased Der p-induced nitric oxide production not via inhibition of iNOS gene in rat alveolar macrophages (NR8383). We determined the expression of macrophage related marker of CD14 and CD36 by RT-PCR in monocyte and macrophage. Our data indicated AZD-9291 was shown to inhibit Der pII-induced gene expression of CD14 and CD36. Furthermore, AZD-9291 activated phosphorylated AMPK, but can’t inhibit Der pII-induced caspase-1. Take together, pur data indicate AZD-9291 alleviates Der pII-stimulated secretion of IL-6 and IL-8 via inhibiting p-AKT /p-STAT3 signaling pathway, NF-κB transloction and AMPK activation. Therefore, AZD-9291 can be developed as a clinical potential drug against Der pII-induced inflammation.

Reference ( 151 ) 〈TOP〉

Acciani TH, Suzuki T, Trapnell BC, Le Cras TD (2016) Epidermal growth factor receptor signalling regulates granulocyte-macrophage colony-stimulating factor production by airway epithelial cells and established allergic airway disease. Clin Exp Allergy 46: 317-328
連結：
Akagawa KS, Komuro I, Kanazawa H, Yamazaki T, Mochida K, Kishi F (2006) Functional heterogeneity of colony-stimulating factor-induced human monocyte-derived macrophages. Respirology 11 Suppl: S32-36
連結：
Alqahtani JM (2016) Asthma and other allergic diseases among Saudi schoolchildren in Najran: the need for a comprehensive intervention program. Ann Saudi Med 36: 379-385
連結：
Antonioli L, Colucci R, Pellegrini C, Giustarini G, Sacco D, Tirotta E, Caputi V, Marsilio I, Giron MC, Nemeth ZH, Blandizzi C, Fornai M (2016) The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders. Expert Opin Ther Targets 20: 179-191
連結：
Ballesteros-Tato A, Randall TD, Lund FE, Spolski R, Leonard WJ, Leon B (2016) T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2 Cell-Mediated Immunity to Inhaled House Dust Mite. Immunity 44: 259-273
連結：

Altmetrics

〈TOP〉

E-mail ：

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

E-mail ：