Am J Respir Cell Mol Biol. 2005 Dec 9; [Epub ahead of print]
Mechanisms of Chlamydophila pneumoniae Mediated GM-CSF Release in Human Bronchial Epithelial Cells.
Krull M, Bockstaller P, Wuppermann FN, Klucken AC, Muhling J, Schmeck B, Seybold J, Walter C, Maass M, Rosseau S, Hegemann JH, Suttorp N, Hippenstiel S.
Department of Internal Medicine/Infectious Diseases, Charite, Universitatsmedizin, Berlin, Germany.
Chlamydophila pneumoniae is an important respiratory pathogen. In this study we characterized C. pneumoniae strain TW183-mediated activation of human small airway epithelial cells (SAEC) and the bronchial epithelial cell line BEAS-2B and demonstrated time-dependent secretion of granulocyte macrophage colony-stimulating factor (GM-CSF) upon stimulation. TW183 activated p38 mitogen activated protein kinase (MAPK) in epithelial cells. Kinase inhibition by SB202190 blocked chlamydia mediated GM-CSF release on mRNA- and protein-level. In addition, the chemical inhibitor as well as dominant negative mutants of p38 MAPK isoforms p38alpha, beta2, and gamma inhibited C. pneumoniae-related NF-kappaB activation. In contrast, blocking of MAPK ERK, c-Jun kinase/JNK or PI-3 Kinase showed no effect on Chlamydia related epithelial cell GM-CSF release. UV-inactivated pathogens as compared to viable bacteria induced a smaller GM-CSF -release suggesting that viable Chlamydia were only partly required for a full effect. Presence of an anti-chlamydial outer membrane protein-A (Omp-A) antibody reduced and addition of recombinant heat-shock protein 60 from C. pneumoniae (cHsp60, GroEL-1) enhanced GM-CSF -release suggesting a role of these proteins in epithelial cell activation. Our data demonstrate that C. pneumoniae triggers an early proinflammatory signaling cascade involving p38 MAPK dependent NF-kappaB activation resulting in subsequent GM-CSF release. C. pneumoniae-induced epithelial cytokine liberation may contribute significantly to inflammatory airway diseases like chronic obstructive pulmonary disease (COPD) or bronchial asthma.
Wow, that one is complex with lots of different things happening in it. Here's the scoop:
This research looks at CPn in the lungs. They wanted to know how CPn triggers inflammation in the lining of the lungs and if they could pinpoint the exact way it triggers this. They discovered that a specific kinase is resposible for this and that if they blocked it, the reaction did not happen. They also discoverd that blocking other kinases did not affect the reaction. Interestingly killed CPn lines still caused a response though smaller. Also the addition of OMP-a antibodies reduced reaction and adding heat shock proteins from CPn made it worse, suggesting that it is not just the CPn that causes reaction in lung tissue but also it's heat shock proteins. This is an abstract so the info is necessarily limited. The take home message is that CPn has several aspects that cause issues for the triggering of the inflammatory cascade