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.
OBJECTIVE
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.


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.
Department of Conservative Dentistry, Dental School, Universidad de Chile, Santiago de Chile, Chile.
Nicolás
N
Dutzan
Jorge
J
Gamonal
Augusto
A
Silva
Mariano
M
Sanz
Rolando
R
Vernal
D016301:Alveolar Bone Loss / Q000276:immunology; D055113:Chronic Periodontitis / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000276:immunology; D018450:Disease Progression; D015536:Down-Regulation / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000032:analysis / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology*; D020381:Interleukin-17 / Q000032:analysis / Q000276:immunology*; D053583:Interleukin-1beta / Q000032:analysis / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000032:analysis / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053245:RANK Ligand / Q000032:analysis / Q000276:immunology*; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000276:immunology; D011988:Receptors, Thyroid Hormone / Q000032:analysis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000032:analysis / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000276:immunology; D000098815:T-bet Transcription Factor
D016207:Cytokines; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D008233:Lymphotoxin-alpha; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053245:RANK Ligand; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma