title: Stimulants of Toll-like receptors 2 and 4 are elevated in saliva of periodontitis patients compared with healthy subjects.
abstract: OBJECTIVE
  Because the absorption of stimulants of Toll-like receptor (TLR)2 and TLR4 from the gastrointestinal tract into the circulation has been proposed to promote the development of atherosclerosis and insulin resistance, we aimed to quantify the abundance of stimulants of TLR2 and TLR4 in human saliva.
  
  
  METHODS
  A recently developed bioassay based upon measurement of NF-κB activation in TLR-deficient human embryonic kidney (HEK)-293 cells transfected with human TLR2 or TLR4 and calibrated with synthetic bacterial lipopeptide (Pam(3) CSK(4) ) or Escherichia coli lipopolysaccharide (LPS), was used to establish the normal range of TLR stimulants in saliva of 20 healthy subjects and 20 subjects with periodontal disease.
  
  
  RESULTS
  Median soluble stimulants of TLR2 and TLR4 were significantly higher in saliva of periodontitis patients compared with saliva of healthy subjects; 3450 versus 77 ng/ml Pam(3) CSK(4) equivalents (p<0.0001) and 138 versus 7 ng/ml LPS equivalents, respectively (p<0.0001). Salivary TLR stimulant levels remained relatively stable in healthy subjects over several days. Six strains of oral Gram-negative bacteria, including Tannerella forsythensis, Lysobacter enzymogenes, Prevotella intermedia, Prevotella oris and Porphyromonas gingivalis, from a panel of nine examined did not stimulate TLR4-dependent signalling.
  
  
  CONCLUSIONS
  Elevated salivary TLR stimulants may represent a novel mechanism by which periodontitis increases the risk of developing cardiovascular disease and insulin resistance.
authors.affiliation: Infection and Immunity section, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: D F
authors.initials: DF
authors.lastname: Lappin
authors.forename: S
authors.initials: S
authors.lastname: Sherrabeh
authors.forename: C
authors.initials: C
authors.lastname: Erridge
mesh_terms: D000328:Adult; D001439:Bacteroides / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D055113:Chronic Periodontitis / Q000276:immunology*; D017077:Culture Media, Conditioned; D004926:Escherichia coli; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D055666:Lipopeptides / Q000032:analysis; D008070:Lipopolysaccharides / Q000032:analysis; D051218:Lymphocyte Antigen 96 / Q000032:analysis; D053528:Lysobacter / Q000276:immunology; D008297:Male; D016966:Porphyromonas gingivalis / Q000276:immunology; D018720:Prevotella / Q000276:immunology; D018713:Prevotella intermedia / Q000276:immunology; D012463:Saliva / Q000737:chemistry*; D012471:Salivary Proteins and Peptides / Q000032:analysis*; D051195:Toll-Like Receptor 2 / Q000032:analysis*; D051197:Toll-Like Receptor 4 / Q000032:analysis*; D051198:Toll-Like Receptor 5 / Q000032:analysis
chemical_list: D017077:Culture Media, Conditioned; C495377:LY96 protein, human; D055666:Lipopeptides; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; C508075:Pam(3)CSK(4) peptide; D012471:Salivary Proteins and Peptides; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5