title: Streptococcus pneumoniae-induced regulation of cyclooxygenase-2 in human lung tissue.
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 prostanoid(4) receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E(2) 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 E(2) formation in human lung tissue may play an important role in the early phase of pneumococcal infections.
authors.affiliation: Dept of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Kolja V
authors.initials: KV
authors.lastname: Szymanski
authors.forename: Mario
authors.initials: M
authors.lastname: Toennies
authors.forename: Anne
authors.initials: A
authors.lastname: Becher
authors.forename: Diana
authors.initials: D
authors.lastname: Fatykhova
authors.forename: Philippe D
authors.initials: PD
authors.lastname: N'Guessan
authors.forename: Birgitt
authors.initials: B
authors.lastname: Gutbier
authors.forename: Frederick
authors.initials: F
authors.lastname: Klauschen
authors.forename: Frank
authors.initials: F
authors.lastname: Neuschaefer-Rube
authors.forename: Paul
authors.initials: P
authors.lastname: Schneider
authors.forename: Jens
authors.initials: J
authors.lastname: Rueckert
authors.forename: Jens
authors.initials: J
authors.lastname: Neudecker
authors.forename: Torsten T
authors.initials: TT
authors.lastname: Bauer
authors.forename: Klaus
authors.initials: K
authors.lastname: Dalhoff
authors.forename: Daniel
authors.initials: D
authors.lastname: Drömann
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Olivia
authors.initials: O
authors.lastname: Kershaw
authors.forename: Bettina
authors.initials: B
authors.lastname: Temmesfeld-Wollbrueck
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Hocke
mesh_terms: D003114:Colony-Forming Units Assay; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D008168:Lung / Q000201:enzymology* / Q000382:microbiology*; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence / Q000379:methods; D011008:Pneumococcal Infections / Q000201:enzymology / Q000382:microbiology*; D011453:Prostaglandins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000378:metabolism*
chemical_list: D011453:Prostaglandins; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone