Treponema denticola peptidoglycan induces the production of inflammatory mediators and matrix metalloproteinase 9 in macrophage-like cells

J Periodontal Res. 2009 Aug;44(4):503-10. doi: 10.1111/j.1600-0765.2008.01141.x. Epub 2008 Oct 22.


Background and objective: Treponema denticola is a key pathogen associated with periodontitis, a chronic inflammatory disease affecting tooth-supporting tissues. In the present study, we investigated the response of human macrophage-like cells to stimulation by peptidoglycan isolated from T. denticola. We also studied the effect of the peptidoglycan preparation on the phosphorylation state of kinases.

Material and methods: Monoblastic leukemia cells (U937 strain) were differentiated into adherent macrophage-like cells using phorbol myristic acid prior to being stimulated for 6 or 24 h with various amounts of T. denticola peptidoglycan. Secreted inflammatory mediators were quantified by enzyme-linked immunosorbent assays. The phosphorylation state of kinases was determined by immunoblotting.

Results: The T. denticola peptidoglycan preparation, which was non-toxic for macrophage-like U937 leukemia cells at the concentration used, significantly increased, in a dose-dependent manner, the secretion of the pro-inflammatory cytokines tumor necrosis factor alpha, interleukin-1beta and interleukin-6. It also increased the secretion of two potent chemokines, interleukin-8 (IL-8) and regulated on activation normal T cell expressed and secreted (RANTES). T. denticola peptidoglycan also induced a significant increase in the secretion of prostaglandin E(2) and matrix metalloproteinase 9 by macrophage-like cells. The phosphorylation state of several kinases, including extracellular regulated protein-serine kinase 2 (+99%), G protein-coupled receptor-serine kinase 2 (+50%), Yes-related protein-tyrosine kinase (+44%) and extracellular regulated protein-serine kinase 1 (+30%) also increased following stimulation with the peptidoglycan preparation.

Conclusion: T. denticola peptidoglycan activates intracellular signaling pathways, leading to an increased production of inflammatory mediators by macrophage-like cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Survival
  • Chemokine CCL5 / analysis
  • Dinoprostone / analysis
  • G-Protein-Coupled Receptor Kinase 2 / analysis
  • Humans
  • Inflammation Mediators / analysis*
  • Interleukin-1beta / analysis
  • Interleukin-6 / analysis
  • Lymphocyte Activation / immunology
  • Macrophages / immunology*
  • Matrix Metalloproteinase 9 / analysis*
  • Mitogen-Activated Protein Kinase 1 / analysis
  • Mitogen-Activated Protein Kinase 3 / analysis
  • Peptidoglycan / immunology*
  • Periodontitis / microbiology
  • Phosphorylation
  • Protein Serine-Threonine Kinases / analysis
  • T-Lymphocytes / immunology
  • Time Factors
  • Treponema denticola / immunology*
  • Tumor Necrosis Factor-alpha / analysis
  • src-Family Kinases / analysis


  • CCL5 protein, human
  • Chemokine CCL5
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Peptidoglycan
  • Tumor Necrosis Factor-alpha
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Protein Serine-Threonine Kinases
  • GRK2 protein, human
  • G-Protein-Coupled Receptor Kinase 2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 9
  • Dinoprostone