Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/33056
標題: Mitogen-activated protein kinases p38 and JNK mediate Actinobacillus pleuropneumoniae exotoxin ApxI-induced apoptosis in porcine alveolar macrophages
作者: Wu, Chi-Ming
Chen, Zeng-Weng
Chen, Ter-Hsin
Liao, Jiunn-Wang
Lin, Cheng-Chung
Chien, Maw-Sheng
Lee, Wei-Cheng
Hsuan, Shih-Ling
關鍵字: Actinobacillus pleuropneumoniae;ApxI;Porcine alveolar macrophage;Apoptosis;Mitogen-activated protein kinase;Caspase;intestinal epithelial-cells;map kinase;pathways;death;phosphorylation;stress
Project: Veterinary Microbiology, Volume 151, Issue 3-4, Page(s) 372-378.
摘要: 
Acanobacillus pleuropneumoniae exotoxins (Apx) are major virulence factors that play important roles in the pathogenesis of pleuropneumonia in swine. A previous study has demonstrated that native ApxI at low concentrations induces apoptosis in primary porcine alveolar macrophages (PAMs) via a caspase-3-dependent pathway. However, the molecular mechanisms underlying ApxI-induced apoptosis remain largely unknown. In this study, it was shown that ApxI treatment in PAMs rapidly induced phosphorylation of both p38 and JNK, members of the mitogen-activated protein kinase family. Application of a selective p38 or JNK inhibitor significantly reduced ApxI-induced apoptosis, indicating the involvement of p38 and JNK pathways in this event. Furthermore, activation of both caspase-8 and -9 were observed in ApxI-stimulated PAMs. Inhibition of caspase-8 and caspase-9 activity significantly protected PAMs from ApxI-induced apoptosis. In addition, Bid activation was also noted in ApxI-treated PAMs, and inhibition of caspase-8 suppressed the activation of Bid and caspase-9, suggesting that ApxI was able to activate the caspases-8-Bid-caspase-9 pathway. Notably, inhibition of p38 or JNK pathway greatly attenuated the activation of caspases-3, -8, and -9. This study is the first to demonstrate that ApxI-induced apoptosis of PAMs involves the activation of p38 and JNK, and engages the extrinsic and intrinsic apoptotic pathways. (C) 2011 Elsevier B.V. All rights reserved.
URI: http://hdl.handle.net/11455/33056
ISSN: 0378-1135
DOI: 10.1016/j.vetmic.2011.03.033
Appears in Collections:獸醫病理生物學所

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