title: Glutaminyl cyclases as novel targets for the treatment of septic arthritis.
abstract: BACKGROUND
  Septic arthritis is a severe and rapidly debilitating disease mainly caused by Staphylococcus aureus. Here, we assess the antiarthritic efficiency of glutaminyl cyclase (QC) inhibitors.
  
  
  METHODS
  Mice were inoculated with an arthritogenic amount of S. aureus intravenously or by local administration into the knee joint. Animals were treated with QC inhibitors (PBD155 and PQ529) via chow during the experiment. QC and isoQC knockout mice were also analyzed for arthritis symptoms after local administration of bacteria.
  
  
  RESULTS
  Both QC inhibitors significantly delayed the onset of clinical signs of arthritis, and inhibitors significantly decreased weight loss in treated animals. Following intraarticular injection of S. aureus, PBD155-treated mice had lower levels of synovitis and bone erosion, as well as less myeloperoxidase in synovial tissue. Fluorescence-activated cell sorter analysis revealed that PBD155 treatment affected the expression pattern of adhesion molecules, preventing the upregulation of cells expressing CD11b/CD18.
  
  
  CONCLUSIONS
  The compounds investigated here represent a novel class of small molecular antiarthritic inhibitors. In our studies, they exerted strong antiinflammatory actions, and therefore they might be suited for disease-modifying treatment of infectious arthritis.
authors.affiliation: Broegelmann Research Laboratory, The Gade Institute,  University of Bergen, Norway.
authors.forename: Annelie
authors.initials: A
authors.lastname: Hellvard
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Maresz
authors.forename: Stephan
authors.initials: S
authors.lastname: Schilling
authors.forename: Sigrid
authors.initials: S
authors.lastname: Graubner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Heiser
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
authors.forename: Holger
authors.initials: H
authors.lastname: Cynis
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Piotr
authors.initials: P
authors.lastname: Mydel
mesh_terms: D000284:Administration, Oral; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D019881:Aminoacyltransferases; C059280:glutaminyl-peptide cyclotransferase