Differental regulation of Moraxella catarrhalis-induced IL-8 response by PKC isoforms

Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease (COPD). In pulmonary epithelial cells, M. catarrhalis induces release of the pro-inflammatory cytokine interleukin 8 (IL-8) which plays a pivotal role in orchestrating airway inflammation. Herein we demonstrate that protein kinase C (PKC) is activated by Moraxella infection and positively regulated M. catarrhalis- triggered NF-κB activation and subsequent IL-8 release. Activation of the PKC/NF-κB signaling pathway was found to be dependent on expression of the Moraxella-specific ubiquitous surface protein (Usp) A2. In addition, we show that specific isoforms of PKC play differential roles in 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 siRNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCΘ increased the M. catarrhalis-induced IL-8 transcription and cytokine release. In conclusion, we show that M. catarrhalis infection activates PKC and its isoforms α, ε and Θ which are differentially regulating IL-8 transcription in human pulmonary epithelial cells.