Abstract
Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. In pulmonary epithelial cells, M. catarrhalis induces release of the pro-inflammatory cytokine interleukin (IL)-8, which plays a pivotal role in orchestrating airway inflammation.
The present study demonstrated that protein kinase (PK)C was activated by Moraxella infection and positively regulated M. catarrhalis-triggered nuclear factor (NF)-κB activation and subsequent IL-8 release. Activation of the PKC/NF-κB signalling pathway was found to be dependent on expression of the Moraxella-specific ubiquitous surface protein A2. In addition, it was shown that specific isoforms of PKC play differential roles in the fine-tuning of the M. catarrhalis-induced NF-κB-dependent gene expression through controlling il8 promoter activity. Inhibition of PKCα and ϵ with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCθ increased, the M. catarrhalis-induced IL-8 transcription and cytokine release.
In conclusion, it was shown that Moraxella catarrhalis infection activates protein kinase C and its isoforms α, ϵ and θ, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.
- Cytokine response
- Moraxella catarrhalis
- protein kinase C isoforms
- pulmonary epithelial cells
- ubiquitous surface protein A2
Footnotes
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