Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/49200
標題: 胸膜肺炎放線桿菌外毒素ApxI 誘發豬肺泡巨噬細胞前炎症細胞素表現之研究
Actinobacillus Pleuropneumoniae Exotoxin ApxI Induces the Expression of Proinflammatory Cytokines in Porcine Alveolar Macrophages
作者: 宣詩玲
關鍵字: 基礎研究
Actinobacillus pleuropneumoniae
生物技術, 畜牧獸醫類
胸膜肺炎放線桿菌
外毒素ApxI
前炎症細胞素
接受體
訊息傳導
exotoxin ApxI
proinflammatory cytokine
receptor
signaltransduction
摘要: 胸膜肺炎放線桿菌為猪隻重要呼吸道病原,引起纖維素性、出血性、壞死性胸膜肺炎,世界各國均有本病發生,往往造成養猪業極大經濟損失。胸膜肺炎放線桿菌產生多種毒性因子,其中外毒素Apx 為造成疾病的主要毒性因子。胸膜肺炎放線桿菌依其血清型不同,生成二至三種外毒素(ApxI-IV),這些外毒素具有不等程度之溶血性及急性細胞毒殺效果。相較於其他Apx 毒素,ApxI 溶血性與細胞毒性均屬最高,為極重要毒性因子,過去本實驗室已證明ApxI 除上述生物活性,尚可誘發猪肺泡巨噬細胞之凋亡,所涉及訊息傳導路徑包括MAPK 成員p38 及JNK 之活化,導致內源性與外源性凋亡路徑活化,進而誘發猪肺泡巨噬細胞凋亡。另利用特異抗體阻斷細胞表面分子CD18 活性,ApxI 所誘發之凋亡亦被抑制,顯示CD18 可能為ApxI 接受體或參與ApxI 誘發之凋亡,並推測此為ApxI 傷害宿主細胞機制之一。至於ApxI 是否尚有其它生物活性如誘發肺泡巨噬細胞前炎症細胞素生成,至今仍無相關研究,故本計劃擬探討: (1) ApxI 是否誘發猪肺泡巨噬細胞表現前炎症細胞素IL-1β、IL-8 及TNF-α;(2)確認ApxI 細胞接受體;(3)釐清相關訊息傳導路徑,包括p38、JNK、NF-κB 在ApxI誘發猪肺泡巨噬細胞前炎症細胞素表現中所扮演的角色及各訊息分子間之交互關係;藉此瞭解ApxI對宿主細胞之生物活性及毒素在胸膜肺炎放線桿菌致病機制扮演之角色,以利本病防治策略之擬定。
Actinobacillus pleuropneumoniae (APP), the causative agent of porcine fibrinous, hemorrhagic,necrotizing pleuropneumonia, has resulted in great economic loss in swine industry worldwide. APPproduces a variety of virulence factors to facilitate its infection. Among various virulence factors, theexotoxins of A. pleuropneumoniae (Apx) are the major virulence factors contributing to the pathogenesis ofthis disease. There are four types of Apx toxins (ApxI-IV) exerting varied degrees of hemolytic and cytotoxicactivities. In comparison with other Apx toxins, ApxI elicits its most significant effects on hemolysis andcytolysis. Previously, we have demonstrated that ApxI induces typical apoptosis in porcine alveolarmacrophages (PAM) at a concentration- and time-dependent manner. The activation of MAPK p38 and JNKby ApxI leads to subsequent involvement of both intrinsic and extrinsic apoptotic pathways. Inhibition ofeither MAPK or caspase activity protected PAM from ApxI-mediated apoptosis. Furthermore, application ofan antibody specifically blocking a cell surface molecule CD18, spared PAM from apoptosis by ApxI,suggesting that CD18 may be a potential receptor of ApxI or may have a role in the apoptotic effect of ApxI.However, up to now whether ApxI confers effects additional to cytolysis and apoptosis on PAM remainsunclear. Therefore, the objectives of proposed study are to: (1) investigate whether ApxI induces theexpression of proinflammatory cytokines IL-1β, IL-8 and TNF-α in PAM; (2) identify the receptor of ApxIon PAM; and (3) delineate the underlying signaling mechanisms involved in the proinflammatory cytokineexpression, including the roles of p38, JNK, and NF-κB, and the correlation between these signalingmolecules. Through the elucidation of ApxI effects on PAM, it would further our understanding toward thepathogenesis of APP and provide useful information in the development of proper strategy for disease controlin the future.
URI: http://hdl.handle.net/11455/49200
其他識別: NSC99-2628-B005-009-MY3
文章連結: http://grbsearch.stpi.narl.org.tw/GRB/result.jsp?id=2103743&plan_no=NSC99-2628-B005-009-MY3&plan_year=99&projkey=PD9907-0855&target=plan&highStr=*&check=0&pnchDesc=%E8%83%B8%E8%86%9C%E8%82%BA%E7%82%8E%E6%94%BE%E7%B7%9A%E6%A1%BF%E8%8F%8C%E5%A4%96%E6%AF%92%E7%B4%A0ApxI+%E8%AA%98%E7%99%BC%E8%B1%AC%E8%82%BA%E6%B3%A1%E5%B7%A8%E5%99%AC%E7%B4%B0%E8%83%9E%E5%89%8D%E7%82%8E%E7%97%87%E7%B4%B0%E8%83%9E%E7%B4%A0%E8%A1%A8%E7%8F%BE%E4%B9%8B%E7%A0%94%E7%A9%B6
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