title: Lipopolysaccharide-binding protein inhibits toll-like receptor 2 activation by lipoteichoic acid in human odontoblast-like cells.
abstract: BACKGROUND
  Previous studies have suggested that odontoblasts sense gram-positive bacteria components through Toll-like receptor 2 (TLR2) and trigger dental pulp immunity by producing proinflammatory cytokines. Currently, the factors that modulate odontoblast TLR2 activation are unknown. Our aim was to investigate lipopolysaccharide-binding protein (LBP) effects on the TLR2-mediated odontoblast response.
  
  
  METHODS
  Human odontoblast-like cells were stimulated with lipoteichoic acid (LTA) (a TLR2 ligand), LBP, CD14 (a TLR2 cofactor), or various combinations of LTA/LBP, LTA/CD14, or LTA/CD14/LBP. CXCL8, IL6, and TLR2 gene expression was assessed by real-time polymerase chain reaction. CXCL8 and interleukin (IL)-6 production was determined by enzyme-linked immunosorbent assay in culture supernatants of cells stimulated with LTA, LTA/CD14, or LTA/CD14/LBP. LBP effects on nuclear factor kappa B (NF-κB), p38, JNK, ERK, STAT3, and p70S6 signaling pathways were determined in LTA-stimulated odontoblast-like cells with a multiplex biometric immunoassay. LBP effects were compared with specific inhibitors of these signaling pathways. LBP transcript and protein were investigated in vivo in healthy and inflamed dental pulps by real-time polymerase chain reaction and immunohistochemistry.
  
  
  RESULTS
  Activation of CXCL8, IL6, and TLR2 gene expression and CXCL8 and IL-6 secretion in LTA- and LTA/CD14-stimulated odontoblast-like cells was significantly decreased by LBP. LBP inhibited NF-κB and p38 signaling pathways in LTA-stimulated cells in a similar way to NF-κB and p38 inhibitors. LBP transcript and protein were detected in vivo in inflamed dental pulps but not in healthy ones.
  
  
  CONCLUSIONS
  These results demonstrate that LBP reduces TLR2-dependent production of inflammatory cytokines by odontoblast-like cells. We suggest that in this way it could modulate host defense in human dental pulp.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, CNRS UMR5242, Equipe Physiopathologie des Odontoblastes, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Carrouel
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Staquet
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Keller
authors.forename: Caroline
authors.initials: C
authors.lastname: Baudouin
authors.forename: Philippe
authors.initials: P
authors.lastname: Msika
authors.forename: Françoise
authors.initials: F
authors.lastname: Bleicher
authors.forename: Brigitte
authors.initials: B
authors.lastname: Alliot-Licht
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Farges
mesh_terms: D000209:Acute-Phase Proteins / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D018929:Cell Culture Techniques; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D016328:NF-kappa B / Q000187:drug effects; D009804:Odontoblasts / Q000187:drug effects* / Q000276:immunology; D011671:Pulpitis / Q000276:immunology; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000187:drug effects; D013682:Teichoic Acids / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D048670:MAP Kinase Kinase 4; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D050796:STAT3 Transcription Factor; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D048051:p38 Mitogen-Activated Protein Kinases; D000099231:Lipopolysaccharide-Binding Protein; C508606:CXCL8 protein, human; C508600:IL6 protein, human; C494086:STAT3 protein, human; C495342:TLR2 protein, human; C009900:lipoteichoic acid
keywords: CD14; CXCL8; IL-6; LBP; NF-κB; Toll-like receptor; human dental pulp; innate immunity; p38; pathogen-associated molecular pattern