Abstract
Chlamydophila pneumoniae alter the expression of Toll-like receptor (TLR) 4 in alveolar type II (ATII)-cells. Subsequently nuclear factor kappaB (NF-κB) is activated and tumor necrosis factor-α (TNF-α) and macrophage inflammatory protein 2 (MIP-2) are produced. Perfluorocarbons (PFC) are beneficial in animals with bacterial pneumonia and reduce production of TNF-α. Using isolated ATII-cells, it was studied whether PFC prevent C. pneumoniae-induced TNF-α and MIP-2 release and what the underlying pathway is. PF5080 preincubation prevented C. pneumoniae-induced secretion of TNF-α (43 ± 10 versus 661 ± 41 pg/mL) and MIP-2 (573 ± 41 versus 4786 ± 502 pg/mL). The C. pneumoniae-induced 2.2-fold increase of TNF-α Receptor 1 expression was reduced by PF5080. C. pneumoniae reduced cytoplasmatic IκBα (3.7 ± 0.3 versus 14 ± 1) and increased NF-κB p65 (31 ± 7.5 versus 3.6 ± 1.1) compared with control. PF5080 prevented NF-κB activation. TLR4 expression was 1.5-fold higher after C. pneumoniae incubation, but remained at control levels after PF5080 pretreatment. After 24 h of C. pneumoniae incubation, in 88 ± 6% of cells bacteria were found in the perinuclear region and in 50% of these cells bacteria adhered to cellular surface. After PF5080 preincubation, C. pneumoniae were in 32 ± 4% attached to and in 5 ± 1% internalized in ATII-cells. Since PF5080 was found in ATII-cell membranes, PF5080 effect could be explained by an alteration of the cellular membrane, preventing activation of the inflammatory cascade.
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Abbreviations
- ATII:
-
alveolar type II
- cHSP60:
-
chlamydial Heat Shock Protein 60
- CLSM:
-
confocal laser scanning microscopy
- MIP-2:
-
macrophage inflammatory protein 2
- NF-κB:
-
nuclear factor kappaB
- PFC:
-
perfluorocarbons
- TLR4:
-
Toll-like receptor 4
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Acknowledgements
The authors thank Ruth Herrmann and Silke Wilitzki (Clinic of Neonatology, Campus Charité Mitte, University Children's Hospital, Humboldt-University Berlin, Germany) Petra Klein (Institute of Biology, Department of Membrane Physiology, Humboldt University Berlin, Germany), and Anke Hellberg (Institute of Medical Microbiology and Hygiene, University of Luebeck, Luebeck, Germany) for technical assistance.
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This study was supported by grants Wi 2074/1-1 from the Deutsche Forschungsgemeinschaft and the “Medizinischer Forschungsfonds Tirol.”
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Wissel, H., Burkhardt, W., Rupp, J. et al. Perfluorocarbons Decrease Chlamydophila pneumoniae–Mediated Inflammatory Responses of Rat Type II Pneumocytes In Vitro. Pediatr Res 60, 264–269 (2006). https://doi.org/10.1203/01.pdr.0000233033.82664.91
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DOI: https://doi.org/10.1203/01.pdr.0000233033.82664.91
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