title: Perfluorocarbons decrease Chlamydophila pneumoniae-mediated inflammatory responses of rat type II pneumocytes in vitro.
abstract: Chlamydophila pneumoniae alter the expression of Toll-like receptor (TLR) 4 in alveolar type II (ATII)-cells. Subsequently nuclear factor kappaB (NF-kappaB) is activated and tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein 2 (MIP-2) are produced. Perfluorocarbons (PFC) are beneficial in animals with bacterial pneumonia and reduce production of TNF-alpha. Using isolated ATII-cells, it was studied whether PFC prevent C. pneumoniae-induced TNF-alpha and MIP-2 release and what the underlying pathway is. PF5080 preincubation prevented C. pneumoniae-induced secretion of TNF-alpha (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-alpha Receptor 1 expression was reduced by PF5080. C. pneumoniae reduced cytoplasmatic IkappaBalpha (3.7 +/- 0.3 versus 14 +/- 1) and increased NF-kappaB p65 (31 +/- 7.5 versus 3.6 +/- 1.1) compared with control. PF5080 prevented NF-kappaB 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.
authors.affiliation: Clinic for Neonatology, Campus Charité Mitte, D-10098 Berlin, Germany.
authors.forename: Heide
authors.initials: H
authors.lastname: Wissel
authors.forename: Wolfram
authors.initials: W
authors.lastname: Burkhardt
authors.forename: Jan
authors.initials: J
authors.lastname: Rupp
authors.forename: Roland R
authors.initials: RR
authors.lastname: Wauer
authors.forename: Mario
authors.initials: M
authors.lastname: Rüdiger
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000187:drug effects / Q000502:physiology*; D005466:Fluorocarbons / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005466:Fluorocarbons; D014409:Tumor Necrosis Factor-alpha