Mitogen-activated protein kinases p38 and JNK mediate Actinobacillus pleuropneumoniae exotoxin ApxI-induced apoptosis in porcine alveolar macrophages.

Abstract

Actinobacillus 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.

• Authors: Chi-Ming Wu, Zeng-Weng Chen, Ter-Hsin Chen, Jiunn-Wang Liao, Cheng-Chung Lin, Maw-Sheng Chien, Wei-Cheng Lee, Shih-Ling Hsuan
• Journal: Veterinary microbiology (Vet Microbiol) Vol. 151 Issue 3-4 Pg. 372-8 (Aug 05 2011) ISSN: 1873-2542 [Electronic] Netherlands
• PMID: 21550186 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• BH3 Interacting Domain Death Agonist Protein
• Bacterial Proteins
• Exotoxins
• Hemolysin Proteins
• ApxI toxin, Bacteria
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Caspase 3
• Caspase 8
• Caspase 9

Topics

• Actinobacillus pleuropneumoniae (metabolism)
• Animals
• Apoptosis
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Bacterial Proteins (pharmacology)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Cells, Cultured
• Enzyme Activation
• Exotoxins (pharmacology)
• Hemolysin Proteins (pharmacology)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• Macrophages, Alveolar (cytology, microbiology)
• Phosphorylation
• Swine
• p38 Mitogen-Activated Protein Kinases (metabolism)