title: The osteoblast as an inflammatory cell: production of cytokines in response to bacteria and components of bacterial biofilms.
abstract: Implant infections are a major complication in the field of orthopaedics. Bacteria attach to the implant-surface and form biofilm-colonies which makes them difficult to treat. Not only immune cells exclusively respond to bacterial challenges, but also local tissue cells are capable of participating in defense mechanisms. The aim of this study was to evaluate the role of osteoblasts in the context of implant infections.
  
  
  
  Primary osteoblasts were cultivated and stimulated with free-swimming bacteria at 4 °C and 37 °C. Supernatants were harvested for ELISA and expression of pro-inflammatory cytokines evaluated by RT-PCR. Bacterial binding to osteoblasts was evaluated using cytofluorometry and uptake was investigated by (3)H thymidine-labelling of bacteria. Osteoblasts were additionally stimulated with the extracellular polymeric substance (EPS) of Staphylococcus epidermidis biofilms, as well as components of the EPS; the bacterial heat shock protein GroEL in particular.
  
  
  
  We demonstrated that binding of bacteria to the osteoblast cell surface leads to an increased production of pro-inflammatory cytokines. Bacteria are capable of surviving intracellular. Furthermore, osteoblasts do not only respond to free-swimming, planktonic bacteria, but also to components of the EPS, including lipoteichoic acid and the heat shock protein GroEL.
  
  
  
  In conclusion, local tissue cells, specifically osteoblasts, might contribute to the persistence of the inflammatory response associated with implant-infections.
authors.affiliation: Center for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, Heidelberg, 69118, Germany. Ulrike.Dapunt@med.uni-heidelberg.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dapunt
authors.affiliation: Institute for Immunology, Heidelberg University, Im Neuenheimer Feld 305, Heidelberg, 69120, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.affiliation: Institute for Immunology, Heidelberg University, Im Neuenheimer Feld 305, Heidelberg, 69120, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegmaier
authors.affiliation: HTRG Heidelberg Trauma Research Group, Center for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, Heidelberg, 69118, Germany.
authors.forename: Arash
authors.initials: A
authors.lastname: Moghaddam
authors.affiliation: Institute for Immunology, Heidelberg University, Im Neuenheimer Feld 305, Heidelberg, 69120, Germany.
authors.forename: Gertrud Maria
authors.initials: GM
authors.lastname: Hänsch
mesh_terms: D018441:Biofilms; D018834:Chaperonin 60; D016207:Cytokines / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D008070:Lipopolysaccharides; D010006:Osteoblasts / Q000502:physiology*; D010587:Phagocytosis; D061251:Primary Cell Culture; D016459:Prosthesis-Related Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000502:physiology*; D013212:Staphylococcus epidermidis / Q000502:physiology*; D013682:Teichoic Acids
chemical_list: D018834:Chaperonin 60; D016207:Cytokines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid
keywords: Biofilm infection; Extracellular polymeric substance; GroEL; Osteoblast