IADR Abstract Archives
The Role of Gingival and Periodontal Ligament Fibroblasts in Inflammo-modultaion
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 hypothesized that periodontal ligament fibroblasts can down regulate inflammation and thus protect teeth.
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, through both contact and secreted factors. Blocking IL6 and IL10 partly restores TNFα secretion, 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 fibroblasts from the gingiva are also able to modulate macrophage TNFα response to P. gingivalis, only PDLF expressed the regulatory transcription factor FoxP3.
Conclusions: Our results indicate that human PDLF regulate inflammation by decreasing the TNFα response of bacterially stimulated macrophages. In addition, PDLF enhance bacterial clearance by improving phagocytosis and may control the extent of the inflammatory cell infiltrate by down-regulating monocyte migration. Amongst the oral fibroblasts tested, PDLF uniquely expressed FoxP3, a transcription factor related to regulation of the adaptive immune system. Our results suggest that oral fibroblasts actively shape the inflammatory microenvironment during periodontal inflammation. A better understanding of the environmental stimuli that control their behavior is important for the understanding of the failed resolution of periodontal and peri-implant inflammation, both of which progress to tissue destruction and bone loss.
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, through both contact and secreted factors. Blocking IL6 and IL10 partly restores TNFα secretion, 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 fibroblasts from the gingiva are also able to modulate macrophage TNFα response to P. gingivalis, only PDLF expressed the regulatory transcription factor FoxP3.
Conclusions: Our results indicate that human PDLF regulate inflammation by decreasing the TNFα response of bacterially stimulated macrophages. In addition, PDLF enhance bacterial clearance by improving phagocytosis and may control the extent of the inflammatory cell infiltrate by down-regulating monocyte migration. Amongst the oral fibroblasts tested, PDLF uniquely expressed FoxP3, a transcription factor related to regulation of the adaptive immune system. Our results suggest that oral fibroblasts actively shape the inflammatory microenvironment during periodontal inflammation. A better understanding of the environmental stimuli that control their behavior is important for the understanding of the failed resolution of periodontal and peri-implant inflammation, both of which progress to tissue destruction and bone loss.