title: Induction of inflammatory cytokines and nitric oxide in J774.2 cells and murine macrophages by lipoteichoic acid and related cell wall antigens from Staphylococcus epidermidis.
abstract: Staphylococcus epidermidis causes infections associated with medical devices including central venous catheters, orthopaedic prosthetic joints and artificial heart valves. This coagulase-negative staphylococcus produces a conventional cellular lipoteichoic acid (LTA) and also releases a short-glycerophosphate-chain-length form of LTA (previously termed lipid S) into the medium during growth. The relative pro-inflammatory activities of cellular and short-chain-length exocellular LTA were investigated in comparison with peptidoglycan and wall teichoic acid from S. epidermidis and LPS from Escherichia coli O111. The ability of these components to stimulate the production of pro-inflammatory cytokines [interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha] and nitric oxide was investigated in a murine macrophage-like cell line (J774.2), and in peritoneal and splenic macrophages. On a weight-for-weight basis the short-chain-length exocellular LTA was the most active of the S. epidermidis products, stimulating significant amounts of each of the inflammatory cytokines and nitric oxide, although it was approximately 100-fold less active than LPS from E. coli. By comparison the full-chain-length cellular LTA and peptidoglycan were less active and the wall teichoic acid had no activity. As an exocellular product potentially released from S. epidermidis biofilms, the short-chain-length exocellular LTA may act as the prime mediator of the host inflammatory response to device-related infection by this organism and act as the Gram-positive equivalent of LPS in Gram-negative sepsis. The understanding of the role of short-chain-length exocellular LTA in Gram-positive sepsis may lead to improved treatment strategies.
authors.affiliation: Molecular Biosciences Research Group, Life and Health Sciences, Aston University, Birmingham B4 7ET, UK 2Department of Clinical Microbiology, Queen Elizabeth Hospital, University Hospital Trust, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Jones
authors.affiliation: Molecular Biosciences Research Group, Life and Health Sciences, Aston University, Birmingham B4 7ET, UK 2Department of Clinical Microbiology, Queen Elizabeth Hospital, University Hospital Trust, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Perris
authors.affiliation: Molecular Biosciences Research Group, Life and Health Sciences, Aston University, Birmingham B4 7ET, UK 2Department of Clinical Microbiology, Queen Elizabeth Hospital, University Hospital Trust, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Vernallis
authors.affiliation: Molecular Biosciences Research Group, Life and Health Sciences, Aston University, Birmingham B4 7ET, UK 2Department of Clinical Microbiology, Queen Elizabeth Hospital, University Hospital Trust, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Worthington
authors.affiliation: Molecular Biosciences Research Group, Life and Health Sciences, Aston University, Birmingham B4 7ET, UK 2Department of Clinical Microbiology, Queen Elizabeth Hospital, University Hospital Trust, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lambert
authors.affiliation: Molecular Biosciences Research Group, Life and Health Sciences, Aston University, Birmingham B4 7ET, UK 2Department of Clinical Microbiology, Queen Elizabeth Hospital, University Hospital Trust, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: Tom Sj
authors.initials: TS
authors.lastname: Elliott
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D013212:Staphylococcus epidermidis; D013682:Teichoic Acids / Q000494:pharmacology*
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D009569:Nitric Oxide; C009900:lipoteichoic acid