Regulation of Salivary Peptidoglycan Recognition Protein 1 in Adolescents.

INTRODUCTION: Peptidoglycan recognition protein 1 (PGLYRP1), a member of peptidoglycan recognition proteins, is known to be involved in the proinflammatory response toward bacterial infections. Recently, PGLYRP1 was identified as a ligand for triggering receptor expressed on myeloid cells 1 (TREM-1). Although PGLYRP1 is involved in immune and inflammatory responses, its levels in initial stages of periodontal disease in adolescents are currently unknown. OBJECTIVES: We aimed to investigate salivary levels of PGLYRP1 and its correlation with TREM-1, polymorphonuclear leukocyte elastase (PMN elastase), and an active matrix metalloproteinase 8 (aMMP-8) in adolescents. METHODS: Whole saliva samples (n = 537) were collected from 15- to 16-y-old adolescents at Kotka Health Center, Finland, prior to periodontal examination, including measurement of periodontal pocket depth (PPD), visible plaque index (VPI), and bleeding on probing (BOP). Adolescents, clustered as periodontally healthy, gingivitis, or subclinical periodontitis, were tested for salivary levels of TREM-1, PGLYRP1, and PMN elastase by enzyme-linked immunosorbent assay and aMMP-8 by a time-resolved immunofluorometric assay (IFMA). RESULTS: Salivary levels of PGLYRP1 and aMMP-8 were significantly higher in adolescents with subclinical periodontitis and gingivitis compared to individuals with healthy periodontium. TREM-1 and PMN elastase levels were higher in adolescents with subclinical periodontitis compared to healthy individuals but did not reach significance. PGLYRP1 correlated positively with BOP, PPD, VPI, aMMP-8, and TREM-1. CONCLUSIONS: Elevated PGLYRP1 levels in adolescents with gingivitis and subclinical periodontitis and its positive correlation with TREM-1 and aMMP-8 may indicate an association of PGLYRP1 with initial stages of periodontal disease. Sex and poor oral hygiene but not smoking are also associated with higher levels of PGLYRP1. However, PGLYRP1 has a lower discriminating capacity and is therefore a less reliable marker alone in the diagnosis of initial stages of periodontal disease in adolescents. KNOWLEDGE TRANSFER STATEMENT: PGLYRP1, a member of peptidoglycan recognition proteins, is a ligand for TREM-1. Elevated PGLYRP1 levels in adolescents with gingivitis and subclinical periodontitis and its positive correlation with TREM-1 and aMMP-8 may indicate an association of PGLYRP1 with initial stages of periodontal disease. However, it has a lower discriminating capacity and is therefore a less reliable marker alone in the diagnosis of periodontal disease in adolescents.

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

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)-1ß 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-1ß 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-1ß 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-1ß (P < 0.025) compared to slow responders. Mixed-effects multilevel regression analyses revealed that PGLYRP1 (P = 0.047) and IL-1ß (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.