Over-expression of forkhead box P3 and its association with receptor activator of nuclear factor-kappa B ligand, interleukin (IL) -17, IL-10 and transforming growth factor-beta during the progression of chronic periodontitis

J Clin Periodontol. 2009 May;36(5):396-403. doi: 10.1111/j.1600-051X.2009.01390.x.

Abstract

Aim: T regulatory (Treg) cells have been detected in periodontitis lesions, and forkhead box P3 (Foxp3) expression has been negatively correlated to receptor activator of nuclear factor-kappa B ligand (RANKL). The aim of this study was to correlate T-helper type 1 (Th1), Th2, Th17 and Treg transcription factor expressions, in gingival tissues from patients undergoing active periodontal tissue destruction, with bone loss-associated cytokines.

Materials and methods: In 10 chronic periodontitis patients undergoing disease progression, the mRNA expressions of T-bet, GATA-3, Foxp3, RORC2, interleukin (IL)-1beta, IL-10, IL-17, RANKL, interferon (IFN)-gamma and transforming growth factor (TGF)-beta1 were quantified using real-time reverse transcription-polymerase chain reaction. The levels of these markers were compared between active and inactive periodontal lesions.

Results: In active periodontal lesions, Foxp3, T-bet, RANKL, IL-17, IL-1beta and IFN-gamma were significantly over-expressed compared with inactive lesions. The expression of IFN-gamma was the highest within the active periodontal lesions, similar to that of TGF-beta1 within the inactive ones. There was a positive correlation between RANKL and IL-17. Additionally, RANKL and IL-17 were positively correlated with RORC2, but no correlation was detected with Foxp3.

Conclusions: These results lead us to speculate that Foxp3(+) cells that do not have a regulatory function might have a role in the pathogenesis of active periodontal lesions by down-regulating TGF-beta1 and IL-10 synthesis that lead to the over-expression of Th17-associated cytokines RANKL and IL-17.

Publication types

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

MeSH terms

  • Alveolar Bone Loss / immunology
  • Chronic Periodontitis / immunology*
  • Cytokines / immunology
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / immunology
  • Disease Progression
  • Down-Regulation / immunology
  • Forkhead Transcription Factors / analysis
  • Forkhead Transcription Factors / immunology*
  • GATA3 Transcription Factor / analysis
  • GATA3 Transcription Factor / immunology
  • Gene Expression Regulation / genetics
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / immunology
  • Interleukin-10 / analysis
  • Interleukin-10 / immunology*
  • Interleukin-17 / analysis
  • Interleukin-17 / immunology*
  • Interleukin-1beta / analysis
  • Interleukin-1beta / immunology
  • Lymphotoxin-alpha / analysis
  • Lymphotoxin-alpha / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RANK Ligand / analysis
  • RANK Ligand / immunology*
  • Receptors, Retinoic Acid / analysis
  • Receptors, Retinoic Acid / immunology
  • Receptors, Thyroid Hormone / analysis
  • Receptors, Thyroid Hormone / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Box Domain Proteins / analysis
  • T-Box Domain Proteins / immunology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Transforming Growth Factor beta1 / analysis
  • Transforming Growth Factor beta1 / immunology

Substances

  • Cytokines
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Interleukin-17
  • Interleukin-1beta
  • Lymphotoxin-alpha
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RANK Ligand
  • RORC protein, human
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transforming Growth Factor beta1
  • Interleukin-10
  • Interferon-gamma