Disease

Taiwanese Study Gives Greater Understanding of App

The mechanisms underlying Actinobacillus pleuropneumoniae (App) exotoxin ApxI in cytokine induction have been investigated by researchers based in Taiwan.

1 February 2011

3 minute read

Zeng-Weng Chen and co-authors at the College of Veterinary Medicine at the National Chung Hsing University in Taipei published a paper on their work in the journal, Veterinary Research.

Actinobacillus pleuropneumoniae (A. pleuropneumoniae; App) causes fibrino-haemorrhagic necrotising pleuropneumonia in pigs, explain the researchers. Production of pro-inflammatory mediators in the lungs is an important feature of A. pleuropneumoniae infection. However, bacterial components other than lipopolysaccharide involved in this process remain unidentified.

The goals of this study were to determine the role of A. pleuropneumoniae exotoxin ApxI in cytokine induction and to delineate the underlying mechanisms.

Using real-time quantitative PCR analysis, we found native ApxI stimulated porcine alveolar macrophages (PAMs) to transcribe mRNAs of IL-1β, IL-8 and TNF-α in a concentration- and time-dependent manner. Heat-inactivation or pre-incubation of ApxI with a neutralising antiserum attenuated ApxI bioactivity to induce cytokine gene expression. The secretion of IL-1β, IL-8 and TNF-α protein from PAMs stimulated with ApxI was also confirmed by quantitative ELISA.

In delineating the underlying signalling pathways contributing to cytokine expression, we observed mitogen-activated protein kinases (MAPKs) p38 and cJun NH2-terminal kinase (JNK) were activated upon ApxI stimulation. Administration of an inhibitor specific to p38 or JNK resulted in varying degrees of attenuation on ApxI-induced cytokine expression, suggesting the differential regulatory roles of p38 and JNK in IL-1β, IL-8 and TNF-α production. Further, pre-incubation of PAMs with a CD18-blocking antibody prior to ApxI stimulation significantly reduced the activation of p38 and JNK, and subsequent expression of IL-1β, IL-8 or TNF-α gene, indicating a pivotal role of β2 integrins in the ApxI-mediated effect.

Collectively, this study demonstrated ApxI induces gene expression of IL-1β, IL-8 and TNF-α in PAMs that involves β2 integrins and downstream MAPKs, concluded Chen and co-authors.

Reference

Chen Z-W., M-S Chien, N-Y Chang, T-H Chen, C-M Wu, C. Huang, W-C Lee and S-L Hsuan. 2011. Mechanisms underlying Actinobacillus pleuropneumoniae exotoxin ApxI induced expression of IL-1β, IL-8 and TNF-α in porcine alveolar macrophages. Veterinary Research, 42:25. doi:10.1186/1297-9716-42-25.