Xylitol, an anticaries agent, exhibits potent inhibition of inflammatory responses in human THP-1-derived macrophages infected with Porphyromonas gingivalis

J Periodontol. 2014 Jun;85(6):e212-23. doi: 10.1902/jop.2014.130455. Epub 2014 Mar 4.

Abstract

Background: Xylitol is a well-known anticaries agent and has been used for the prevention and treatment of dental caries. In this study, the anti-inflammatory effects of xylitol are evaluated for possible use in the prevention and treatment of periodontal infections.

Methods: Cytokine expression was stimulated in THP-1 (human monocyte cell line)-derived macrophages by live Porphyromonas gingivalis, and enzyme-linked immunosorbent assay and a commercial multiplex assay kit were used to determine the effects of xylitol on live P. gingivalis-induced production of cytokine. The effects of xylitol on phagocytosis and the production of nitric oxide were determined using phagocytosis assay, viable cell count, and Griess reagent. The effects of xylitol on P. gingivalis adhesion were determined by immunostaining, and costimulatory molecule expression was examined by flow cytometry.

Results: Live P. gingivalis infection increased the production of representative proinflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β, in a multiplicity of infection- and time-dependent manner. Live P. gingivalis also enhanced the release of cytokines and chemokines, such as IL-12 p40, eotaxin, interferon γ-induced protein 10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1. The pretreatment of xylitol significantly inhibited the P. gingivalis-induced cytokines production and nitric oxide production. In addition, xylitol inhibited the attachment of live P. gingivalis on THP-1-derived macrophages. Furthermore, xylitol exerted antiphagocytic activity against both Escherichia coli and P. gingivalis.

Conclusion: These findings suggest that xylitol acts as an anti-inflammatory agent in THP-1-derived macrophages infected with live P. gingivalis, which supports its use in periodontitis.

Keywords: Cytokines; Porphyromonas gingivalis; inflammation; periodontitis; xylitol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Bacterial Adhesion / drug effects
  • Cell Count
  • Cell Line
  • Cell Survival / drug effects
  • Chemokine CCL2 / drug effects
  • Chemokine CXCL10 / drug effects
  • Chemokines, CC / drug effects
  • Cytokines / drug effects
  • Escherichia coli / drug effects
  • Humans
  • Immunodominant Epitopes / drug effects
  • Immunologic Factors / pharmacology
  • Interleukin-12 / analysis
  • Interleukin-1beta / drug effects
  • Macrophage Inflammatory Proteins / drug effects
  • Macrophages / drug effects*
  • Macrophages / microbiology
  • Monocytes / immunology
  • Nitric Oxide / analysis
  • Peptide Fragments / drug effects
  • Phagocytosis / drug effects
  • Porphyromonas gingivalis / drug effects*
  • Porphyromonas gingivalis / immunology
  • Tumor Necrosis Factor-alpha / drug effects
  • Xylitol / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CXCL10
  • Chemokines, CC
  • Cytokines
  • Immunodominant Epitopes
  • Immunologic Factors
  • Interleukin-1beta
  • Macrophage Inflammatory Proteins
  • P40, iodinated C-terminal peptide, human
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Nitric Oxide
  • Xylitol