title: Expression of NOD2 is increased in inflamed human dental pulps and lipoteichoic acid-stimulated odontoblast-like cells.
abstract: Human odontoblasts trigger immune response s to oral bacteria that invade dental tissues during the caries process. To date, their ability to regulate the expression of the nucleotide-binding domain leucine-rich repeat containing receptor NOD2 when challenged by Gram-positive bacteria is unknown. In this study, we investigated NOD2 expression in healthy and inflamed human dental pulps challenged by bacteria, and in cultured odontoblast-like cells stimulated with lipoteichoic acid (LTA), a Toll-like receptor (TLR) 2 agonist which is specific for Gram-positive bacteria. We found that NOD2 gene expression was significantly up-regulated in pulps with acute inflammation compared to healthy ones. In vitro, LTA augmented NOD2 gene expression and protein level in odontoblast-like cells. The increase was more pronounced in odontoblast-like cells compared to dental pulp fibroblasts. Blocking experiments in odontoblast-like cells with anti-TLR2 antibody strongly reduced the NOD2 gene expression increase, whereas stimulation with the synthetic TLR2 ligand Pam(2)CSK(4) confirmed NOD2 gene up-regulation following TLR2 engagement. These data suggest that NOD2 up-regulation is part of the odontoblast immune response to Gram-positive bacteria and might be important in protecting human dental pulp from the deleterious effects of cariogenic pathogens.
authors.affiliation: Université de Lyon, Université Lyon 1, and Hospices Civils de Lyon, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Keller
authors.forename: Florence
authors.initials: F
authors.lastname: Carrouel
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Staquet
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kufer
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: Jean-Christophe
authors.initials: JC
authors.lastname: Farges
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008963:Molar / Q000166:cytology / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D009804:Odontoblasts / Q000187:drug effects / Q000378:metabolism*; D011671:Pulpitis / Q000378:metabolism*; D013682:Teichoic Acids / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; C508606:CXCL8 protein, human; D002352:Carrier Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C499841:PAM2-Cys-SKKK; C495342:TLR2 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid