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

Dutzan N, Gamonal J, Silva A, Sanz M, Vernal R. 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; 36: 396-403. doi: 10.1111/j.1600-051X.2009.01390.x. 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. In 10 chronic periodontitis patients undergoing disease progression, the mRNA expressions of T-bet, GATA-3, Foxp3, RORC2, interleukin (IL)-1 beta, IL-10, IL-17, RANKL, interferon (IFN)-gamma and transforming growth factor (TGF)-beta 1 were quantified using real-time reverse transcription-polymerase chain reaction. The levels of these markers were compared between active and inactive periodontal lesions. In active periodontal lesions, Foxp3, T-bet, RANKL, IL-17, IL-1 beta 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-beta 1 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. 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-beta 1 and IL-10 synthesis that lead to the over-expression of Th17-associated cytokines RANKL and IL-17.