Expression of NOD2 Is Increased in Inflamed Human Dental Pulps and Lipoteichoic Acid-Stimulated Odontoblast-Like Cells

Innate Immun. 2011 Feb;17(1):29-34. doi: 10.1177/1753425909348527. Epub 2009 Oct 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Carrier Proteins / pharmacology
  • Cells, Cultured
  • Dental Pulp / cytology
  • Dental Pulp / metabolism*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Humans
  • Interleukin-8 / genetics
  • Lipopolysaccharides / pharmacology*
  • Molar / cytology
  • Molar / metabolism
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Odontoblasts / drug effects
  • Odontoblasts / metabolism*
  • Pulpitis / metabolism*
  • Teichoic Acids / pharmacology*
  • Toll-Like Receptor 2 / antagonists & inhibitors
  • Toll-Like Receptor 2 / immunology
  • Tumor Necrosis Factor-alpha / genetics


  • Antibodies, Monoclonal
  • CXCL8 protein, human
  • Carrier Proteins
  • Interleukin-8
  • Lipopolysaccharides
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • PAM2-Cys-SKKK
  • TLR2 protein, human
  • Teichoic Acids
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha
  • lipoteichoic acid