Ability of supragingival plaque to induce toll-like receptor 4-mediated stimulation is associated with cytokine production by peripheral blood mononuclear cells.

BACKGROUND

In our previous study, we found that the ability of supragingival plaque to induce Toll-like receptor (TLR)4-mediated stimulation was positively associated with plaque score and bleeding on probing (BOP) at the sampled sites and that the ability to induce TLR2-mediated stimulation was negatively associated with probing depth (PD) and clinical attachment level (CAL). Because signaling from TLR leads to the induction of pro- and anti-inflammatory cytokines, we further analyzed the influence of the ability of supragingival plaque to induce TLR2-/TLR4-mediated stimulation of cytokine production by peripheral blood mononuclear cells (PBMCs).

METHODS

The abilities of 125 plaque samples to induce TLR2- or TLR4-mediated stimulation were determined using genetically engineered Chinese hamster ovary reporter cells that express a reporter molecule upon activation of nuclear factor-kappa B through TLR2 or TLR4. PBMCs were stimulated with each plaque sample, and the production of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin [IL]-6 and -8) and an anti-inflammatory cytokine (IL-10) was analyzed by enzyme-linked immunosorbent assay.

RESULTS

The levels of the cytokines produced by PBMCs all correlated with the ability of supragingival plaque to induce TLR4-mediated stimulation but not with its ability to induce TLR2-mediated stimulation. Cytokine production was inhibited by an anti-TLR4 monoclonal antibody and a TLR4 antagonist, compound 406. The levels of cytokines were associated with plaque index, BOP, PD, and CAL at the sampled sites.

CONCLUSIONS

The production of pro-/anti-inflammatory cytokines by PBMCs was associated with the ability of supragingival plaque to induce TLR4-mediated stimulation. The cytokines induced by supragingival plaque via TLR4 might modulate periodontal status.