Mechanisms of Chlamydophila pneumoniae-mediated GM-CSF release in human bronchial epithelial cells.

Abstract

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 levels. 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. Ultraviolet-inactivated pathogens as compared with viable bacteria induced a smaller GM-CSF release, suggesting that viable Chlamydiae were only partly required for a full effect. Presence of an antichlamydial outer membrane protein-A (OmpA) 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.

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@article{Kruell2006MechanismsOC, title={Mechanisms of Chlamydophila pneumoniae-mediated GM-CSF release in human bronchial epithelial cells.}, author={Matthias Kruell and Petra Bockstaller and Frederik N. Wuppermann and Andrea C. Klucken and Joerg Muehling and Bernd Schmeck and Joachim Seybold and Clemens Walter and Matthias Maass and Simone Rosseau and Johannes H. Hegemann and Norbert Suttorp and Stefan Hippenstiel}, journal={American journal of respiratory cell and molecular biology}, year={2006}, volume={34 3}, pages={375-82} }