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

Abstract

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.

• Authors: S-I Tanabe, C Bodet, D Grenier
• Journal: Journal of periodontal research (J Periodontal Res) Vol. 44 Issue 4 Pg. 503-10 (Aug 2009) ISSN: 1600-0765 [Electronic] United States
• PMID: 18973520 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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)