Abstract
The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue.
Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites.
In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid4 receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E2 related pro- and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection.
Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E2 formation in human lung tissue may play an important role in the early phase of pneumococcal infections.
Footnotes
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Support Statement
This study was supported by the Transregional Collaborative Research Center SFB-TR84 of the Deutsche Forschungsgemeinschaft (grants C5 to A.C. Hocke and S. Hippenstiel, Z1a to A.C. Hocke and Z1b to A.D. Gruber) and the German Federal Ministry of Education and Research (grant C8 to A.C. Hocke; PROGRESS – Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis).
Statement of Interest
None declared.
- Received October 26, 2011.
- Accepted February 23, 2012.
- ©ERS 2012