Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. In pulmonary epithelial cells, M. catarrhalis induces release of the proinflammatory 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)-kB activation and subsequent IL-8 release. Activation of the PKC/NF-kB 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 NFkB-dependent gene expression through controlling il8 promoter activity. Inhibition of PKCa and e with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCh 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 a, e and h, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.
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