Roles of TLR2, TLR4, NOD2, and NOD1 in pulp fibroblasts

J Dent Res. 2009 Aug;88(8):762-7. doi: 10.1177/0022034509341779.

Abstract

Pulp fibroblasts express various pro-inflammatory mediators leading to marked infiltration of inflammatory cells in the progression of pulpitis. We hypothesized that pulp fibroblasts play roles in the recognition of invaded caries-related bacteria and the subsequent innate immune responses. We found clear expressions of TLR2, NOD1, and NOD2 and a faint expression of TLR4 in human dental pulp fibroblasts (HDPF) by RT-PCR and flow cytometry. We also observed that various pro-inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostaglandin E(2) and its key enzyme COX-2, not iNOS or caspase-1, were markedly up-regulated by stimulation with these TLR and NOD agonists. More over, the NOD2 agonist acted synergistically with the TLR2, not the TLR4, agonist to stimulate the production of pro-inflammatory mediators in HDPF. These findings indicate that TLR2, TLR4, NOD2, and NOD1 in HDPF are functional receptors, and NOD2 is a modulator of signals transmitted through TLR2 in pulpal immune responses, leading to progressive pulpitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
  • Apoptosis / immunology*
  • Cells, Cultured
  • Chemokine CCL2 / analysis
  • Chemokine CXCL10 / analysis
  • Cyclooxygenase 2 / immunology
  • Dental Pulp / cytology
  • Dental Pulp / immunology*
  • Diaminopimelic Acid / analogs & derivatives
  • Dinoprostone / analysis
  • Escherichia coli
  • Fibroblasts / immunology*
  • Humans
  • Inflammation Mediators / immunology
  • Interleukin-6 / analysis
  • Interleukin-8 / analysis
  • Lipopeptides / pharmacology
  • Lipopolysaccharides / pharmacology
  • Nod1 Signaling Adaptor Protein / analysis*
  • Nod1 Signaling Adaptor Protein / antagonists & inhibitors
  • Nod2 Signaling Adaptor Protein / analysis*
  • Nod2 Signaling Adaptor Protein / antagonists & inhibitors
  • Pulpitis / immunology
  • Signal Transduction / immunology
  • Streptococcus mutans / immunology
  • Toll-Like Receptor 2 / analysis*
  • Toll-Like Receptor 2 / antagonists & inhibitors
  • Toll-Like Receptor 4 / analysis*
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Vascular Cell Adhesion Molecule-1 / analysis

Substances

  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CXCL10
  • Inflammation Mediators
  • Interleukin-6
  • Interleukin-8
  • Lipopeptides
  • Lipopolysaccharides
  • NOD1 protein, human
  • NOD2 protein, human
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Pam(3)CSK(4) peptide
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Vascular Cell Adhesion Molecule-1
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Diaminopimelic Acid
  • N(2)-(gamma-D-glutamyl)-meso-2,2'-diaminopimelic acid
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone