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.
Yamaguchi
Ryusuke
R
Department of Periodontology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yoshimura
Atsutoshi
A
Yoshioka
Hidenobu
H
Kaneko
Takashi
T
Hara
Yoshitaka
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000032:analysis*; D003773:Dental Plaque / Q000276:immunology*; D003774:Dental Plaque Index; D005260:Female; D005884:Gingival Hemorrhage / Q000276:immunology; D006017:Glycolipids / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis; D017622:Periodontal Attachment Loss / Q000276:immunology; D010512:Periodontal Index; D010514:Periodontal Pocket / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055815:Young Adult
D000911:Antibodies, Monoclonal; D016207:Cytokines; D006017:Glycolipids; D015850:Interleukin-6; D016209:Interleukin-8; D008050:Lipid A; D016328:NF-kappa B; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C040142:lipid A precursors, bacterial; D016753:Interleukin-10