title: Inhibition of apoptosis in neuronal cells infected with Chlamydophila (Chlamydia) pneumoniae.
abstract: BACKGROUND
  Chlamydophila (Chlamydia) pneumoniae is an intracellular bacterium that has been identified within cells in areas of neuropathology found in Alzheimer disease (AD), including endothelia, glia, and neurons. Depending on the cell type of the host, infection by C. pneumoniae has been shown to influence apoptotic pathways in both pro- and anti-apoptotic fashions. We have hypothesized that persistent chlamydial infection of neurons may be an important mediator of the characteristic neuropathology observed in AD brains. Chronic and/or persistent infection of neuronal cells with C. pneumoniae in the AD brain may affect apoptosis in cells containing chlamydial inclusions.
  
  
  RESULTS
  SK-N-MC neuroblastoma cells were infected with the respiratory strain of C. pneumoniae, AR39 at an MOI of 1. Following infection, the cells were either untreated or treated with staurosporine and then examined for apoptosis by labeling for nuclear fragmentation, caspase activity, and membrane inversion as indicated by annexin V staining. C. pneumoniae infection was maintained through 10 days post-infection. At 3 and 10 days post-infection, the infected cell cultures appeared to inhibit or were resistant to the apoptotic process when induced by staurosporine. This inhibition was demonstrated quantitatively by nuclear profile counts and caspase 3/7 activity measurements.
  
  
  CONCLUSIONS
  These data suggest that C. pneumoniae can sustain a chronic infection in neuronal cells by interfering with apoptosis, which may contribute to chronic inflammation in the AD brain.
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology, Philadelphia College of Osteopathic Medicine, Philadelphia, USA. Denaha@pcom.edu
authors.forename: Denah M
authors.initials: DM
authors.lastname: Appelt
authors.forename: Maria R
authors.initials: MR
authors.lastname: Roupas
authors.forename: Deana S
authors.initials: DS
authors.lastname: Way
authors.forename: Marcus G
authors.initials: MG
authors.lastname: Bell
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Albert
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Hammond
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Balin
mesh_terms: D000544:Alzheimer Disease / Q000382:microbiology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000473:pathology; D002467:Cell Nucleus / Q000382:microbiology / Q000473:pathology; D002690:Chlamydia Infections / Q000382:microbiology*; D016993:Chlamydophila pneumoniae / Q000502:physiology*; D053938:DNA Fragmentation; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000382:microbiology* / Q000473:pathology / Q000502:physiology*; D013997:Time Factors
chemical_list: D017304:Annexin A5; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D020169:Caspases