The role of gingival and periodontal ligament fibroblasts in modulation of inflammation

Objectives: Up to 59% of the patients receiving dental implants will experience peri-implantitis within 10 years of implant use. Peri-implantitis progresses faster and is more extensive and less responsive to treatment compared to periodontitis. Due to the absence of the periodontal ligament around dental implants as opposed to natural teeth, we aimed to examine whether periodontal ligament fibroblasts actively modulate inflammation.
Methods: Primary human periodontal ligament and gingival fibroblasts (PDLF and GF) were harvested from extracted teeth of healthy donors. Human macrophages were stimulated with Porphyromonas gingivalis in the absence or presence of oral fibroblasts. The effect of fibroblast co-culture on macrophage phagocytosis and cytokine secretion were evaluated. In addition, we examined the effect of fibroblasts on SDF-1α mediated monocyte migration.
Results: PDLF down regulate TNFα secretion by bacterially stimulated macrophages, in both a contact and a secretion dependent manner. Blocking IL6 and IL10 partly restores TNF α secretion following bacterial stimulation, suggesting that these secreted factors participate in the regulation. In addition, PDLF down-regulate monocyte migration towards a chemotactic gradient (SDF-1α) and increase phagocytosis of Porphyromonas gingivalis. Although an immortalized human GF cell line was less effective than PDLF, primary GF showed a more potent regulatory effect than PDLF from the same donors. Furthermore, priming fibroblasts with an inflammatory signal maximized their regulatory activity under the conditions tested.
Conclusions: Our results indicate that PDLF and GF harvested from healthy patients have the potential to regulate inflammation by decreasing pro-inflammatory cytokine secretion from immune cells exposed to bacterial stimulation. In addition, PDLF may control the extent of the inflammatory cell infiltrate by down-regulating monocyte migration. Furthermore, PDLF improve bacterial clearance by enhancing phagocytosis. We aim to investigate the regulatory properties of fibroblasts from inflamed peri-implant tissues in order to understand the failure of these fibroblasts to dampen the severity of inflammation and its outcome.