Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms.

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)-kappaB activation and subsequent IL-8 release. Activation of the PKC/NF-kappaB 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-kappaB-dependent gene expression through controlling il8 promoter activity. Inhibition of PKCalpha and epsilon with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCtheta 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 alpha, epsilon and theta, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.

• Authors: H Slevogt, L Maqami, K Vardarowa, W Beermann, A C Hocke, J Eitel, B Schmeck, A Weimann, B Opitz, S Hippenstiel, N Suttorp, P D N'Guessan
• Journal: The European respiratory journal (Eur Respir J) Vol. 31 Issue 4 Pg. 725-35 (Apr 2008) ISSN: 1399-3003 [Electronic] England
• PMID: 18184679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-8
• Isoenzymes
• PRKCQ protein, human
• Protein Kinase C
• Protein Kinase C-alpha
• Protein Kinase C-epsilon
• Protein Kinase C-theta

Topics

• Bronchi (cytology, immunology)
• Cell Line
• Epithelial Cells (immunology)
• Gene Expression Regulation (immunology)
• Humans
• Interleukin-8 (metabolism)
• Isoenzymes (immunology)
• Moraxella catarrhalis (pathogenicity)
• Moraxellaceae Infections (immunology)
• Promoter Regions, Genetic
• Protein Kinase C (immunology)
• Protein Kinase C-alpha (immunology)
• Protein Kinase C-epsilon (immunology)
• Protein Kinase C-theta
• Signal Transduction (immunology)