Regulation of PGLYRP1 and TREM-1 during Progression and Resolution of Gingival Inflammation

Abstract

Introduction: The triggering receptor expressed on myeloid cells 1 (TREM-1) signaling pathway is stimulated by bacteria and, together with its putative ligand peptidoglycan recognition protein 1 (PGLYRP1), propagates proinflammatory responses. Objectives: We aimed to evaluate the TREM-1/PGLYRP1/interleukin (IL)–1β regulation in response to biofilm accumulation and removal in an experimental human gingivitis model. Methods: The study (n = 42 participants, mean age: 23.8 ± 3.7 y) comprised a recruitment step (day –14) followed by experimentally induced biofilm formation (induction [I] phase, day 0 to +21) and a 2-wk resolution (R) phase (day +21 to +35). Plaque was recorded by the Modified Quigley and Hein Plaque Index (TQHPI), while records of gingival inflammation were based on the Modified Gingival Index (MGI). Unstimulated whole saliva supernatants (n = 210, 5 time points) were tested for TREM-1, PGLYRP1, and IL-1β by enzyme-linked immunosorbent assay. Results: During the I-phase, concentrations of all analytes showed a tendency for downregulation at day +7 compared to day 0. TREM-1 (P = 0.019) and PGLYRP1 (P = 0.007) increased significantly between day +7 and day +21. Although all analyte levels decreased during the R-phase, the difference was not significant except TREM-1 being at borderline significance (P = 0.058). Moreover, TREM-1, PGLYRP1, and IL-1β showed significant positive correlations (P < 0.0001) with each other. The study participants were grouped into “fast” and “slow” responders based on clinical gingival inflammation scores. At each time point, fast responders showed significantly higher concentrations of TREM-1 (P < 0.025), PGLYRP1 (P < 0.007), and IL-1β (P < 0.025) compared to slow responders. Mixed-effects multilevel regression analyses revealed that PGLYRP1 (P = 0.047) and IL-1β (P = 0.005) showed a significant positive association with the MGI scores. Conclusion: The study demonstrated that TREM-1 and PGLYRP1 are regulated in response to biofilm accumulation and removal, and fast responders demonstrated higher levels of these analytes compared to slow responders. Knowledge Transfer Statement: The results of this study demonstrated the suitability of salivary TREM-1 and PGLYRP1 to reflect biofilm accumulation and removal and PGLYRP1 to monitor the progression and resolution of inflammation in gingivitis-susceptible individuals (fast responders). Combined with conventional risk factors, the molecular toolbox proposed here should be further validated in future studies to confirm whether it can be used for population-based monitoring and prevention of gingivitis.

The relationship between oral diseases and infectious complications in patients under dialysis

“…Although the main, physiological functions of PGLYRP1 are still ambiguous, PGLYRP1 can be induced in response to systemic infection (Osanai et al, ). Recent work by Silbereisen et al demonstrated that the levels of PGLYRP1 were upregulated in saliva in response to experimental dental plaque accumulation (Silbereisen et al, ). Although PGLYRP1 has antibacterial activities against gram‐positive bacteria, the linking of salivary or serum PGLYRP1 to systemic infection episodes during HD was not previously demonstrated (Lu et al, ; Wang et al, ).…”

Salivary biomarkers in the context of gingival inflammation in children with cystic fibrosis

“…TREM-1, PGLYRP1, and IL-1 are also known to be regulated during gingival inflammation. 22 This fact together with our findings that the periodontal status seemingly does not affect salivary calprotectin levels, might explain why calprotectin did not correlate with TREM-1, PGLYRP1, and IL-1 in systemic health. In CF children, however, PGLYRP1, IL-1 , and calprotectin positively correlated with each other.…”

“…Salivary TREM-1, PGLYRP1, calprotectin, and IL-1 levels were analyzed by commercial enzyme-linked immunosorbent assay (ELISA) kits *, †, ‡, § according to the manufacturer's instructions and as described previously. 22 The TREM-1 ELISA kit is detecting both soluble and membrane-bound TREM-1. Briefly, standards and diluted saliva SNs (TREM-1 (1:3), PGLYRP1 (1:60), calprotectin (1:2,000), and IL-1 (1:20)) were applied to pre-coated (capturing antibodies) 96 well plates (Nunc-Immuno MicroWell 96 well solid plates, Sigma) and incubated for 2 hours at room temperature (RT) after washing and blocking the plates.…”

Label‐Free Quantitative Proteomics versus Antibody‐Based Assays to Measure Neutrophil‐Derived Enzymes in Saliva

“…Differences in analyte levels over time (day 0 to +35) were investigated by Friedman's test, and Dunn's multiple comparisons test was used to compare analyte levels between individual time points. Mixed‐effects multilevel regression analyses were performed using the software STATA 14.2 (StataCorp) to estimate differences in gingival inflammation (MGI) and plaque (TQHPI) over time. p ‐Values < 0.05 were considered statistically significant.…”