Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms.
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.
Slevogt
H
H
Dept of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. hortense.slevogt@charite.de
Maqami
L
L
Vardarowa
K
K
Beermann
W
W
Hocke
A C
AC
Eitel
J
J
Schmeck
B
B
Weimann
A
A
Opitz
B
B
Hippenstiel
S
S
Suttorp
N
N
N'Guessan
P D
PD
D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007527:Isoenzymes / Q000276:immunology*; D001936:Moraxella catarrhalis / Q000472:pathogenicity; D045828:Moraxellaceae Infections / Q000276:immunology*; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000276:immunology*; D051571:Protein Kinase C-alpha / Q000276:immunology*; D051744:Protein Kinase C-epsilon / Q000276:immunology*; D000074121:Protein Kinase C-theta; D015398:Signal Transduction / Q000276:immunology
D016209:Interleukin-8; D007527:Isoenzymes; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta