Introduction: Periodontitis, a major cause of tooth loss, is a bacterially induced inflammatory disease affecting the tissues surrounding and supporting the teeth, whose molecular basis is poorly understood. Accumulation of dental plaque initiates the disease, and its progression to severe states has been associated with certain species of bacteria.
Objectives: Our aim is to identify the epithelial mechanisms activated by commensal species and periodontal pathogens to determine which signalling pathways, transcription factors, and pro-inflammatory cytokine responses are associated with periodontitis.
Methods: The H400 gingival epithelial cell line was infected with the health associated Actinomyces naeslundii and periodontopathogens Fusobacterium nucleatum and Porphyromonas gingivalis for either up to 2 h for signal pathway activation or 24 h cytokine release.
Results: Differential pathway activation was observed between the three species. A. naeslundii induced phosphorylation of JNK, ERK 1/2 and NF-κB, similarly to F. nucleatum which activated all MAP kinase pathways (including p38) and NF-κB. P. gingivalis induced minimal levels of p-JNK and p-ERK 1/2, and differential transcription factor activation was observed in response to the three bacteria. A. naeslundii and F. nucleatum exhibited a similar profile with activation of c-Fos and c-Jun, while P. gingivalis activated binding of ATF-2, MEF-2 and STAT 1α. Notably, F. nucleatum was the most potent activator. Both A. naeslundii and F. nucleatum induced a pro-inflammatory response, with A. naeslundii driving release of IL-1α, IL-1β and IL-6, and F. nucleatum stimulating IL-6 and GM-CSF secretion. P. gingivalis was the least stimulatory bacterium, an observation supported by a lack of cytokine production and IL-8 down-regulation.
Conclusion: Our data suggests that epithelial cells recognize and respond differently to commensal bacteria compared to periodontal pathogens. Elucidating the mechanisms by which this happens will form the basis of our future studies.