lipid-a and Gingival-Hemorrhage

We hypothesized that tobacco smoke induces alterations to the 3-OH fatty acids present in lipid A in a manner consistent with a microflora of reduced inflammatory potential. Whole saliva samples and full-mouth clinical periodontal recordings were obtained from persons with (22 smokers; 15 non-smokers) and without (14 smokers; 15 non-smokers) chronic periodontitis. Clear differences in the contributions of multiple saturated 3-OH fatty acid species were noted in the group with disease compared with healthy individuals. Increases in the long-chain fatty acids associated with anaerobic bacterial periodontopathogens, particularly 3-OH-C(i17.0) (146.7%, relative to controls), were apparent. Significant reductions in the 3-OH fatty acids associated with the consensus (high potency) enteric LPS structure (3-OH-C(12.0) and 3-OH-C(14.0); 33.3% and 15.8% reduction, respectively) were noted in smokers compared with non-smokers with chronic periodontitis. Thus, smoking is associated with specific structural alterations to the lipid-A-derived 3-OH fatty acid profile in saliva that are consistent with an oral microflora of reduced inflammatory potential. These findings provide much-needed mechanistic insight into the established clinical conundrum of increased infection with periodontal pathogens but reduced clinical inflammation in smokers.

Topics: Adult; Bacteria, Anaerobic; Chronic Periodontitis; Cotinine; Dental Plaque Index; Fatty Acids; Female; Gingival Hemorrhage; Gram-Negative Bacteria; Humans; Lipid A; Lipopolysaccharides; Male; Middle Aged; Mouth; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Saliva; Smoking

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).. 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.. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; CHO Cells; Cricetinae; Cricetulus; Cytokines; Dental Plaque; Dental Plaque Index; Female; Gingival Hemorrhage; Glycolipids; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lipid A; Male; Middle Aged; NF-kappa B; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Young Adult