Triggering Receptor Expressed On Myeloid Cells-1 Levels Research Articles

Value of gingival crevicular fluid TREM-1, PGLYRP1, and IL-1β levels during menopause.

This study aimed to investigate the association of GCF TREM-1, PGLYRP1, and IL-1β levels with periodontal health in pre- and postmenopausal women. Triggering receptor expressed on myeloid cells 1 (TREM-1), activated through its ligand peptidoglycan recognition protein 1 (PGLYRP1), stimulates proinflammatory cytokine production, such as interleukin (IL)-1β, during periodontal inflammation. Postmenopausal changes may modulate these immune-inflammatory functions. No clinical study has yet investigated the effect of menopause on TREM-1, PGLYRP1, and IL-1β levels in gingival crevicular fluid (GCF). This cross-sectional study included 148 women (age range = 35-65 years), divided into postmenopausal women (PMW) (n = 76, mean age = 54 ± 5 years) and regularly menstruating premenopausal women (RMPW) (n = 72, mean age = 40 ± 4 years). Clinical periodontal parameters were recorded. TREM-1, PGLYRP1, and IL-1β levels were quantified with enzyme-linked immunosorbent assays. Pearson's Chi-squared test and Mann-Whitney-U test were used to compare categorical and numerical variables, respectively. Spearman's Rho correlation analysis was used to test the linear relationship between variables. Analyte level data were categorized based on the periodontal diagnosis and menopause status (2 × 2 nonparametric factorial ANOVA). No significant differences in TREM-1, PGLYRP1, and IL-1β levels between PMW and RMPW were observed (p > .05). Mean values of periodontal indexes including probing depth did not differ significantly between PMW and RMPW groups (p = .474). TREM-1 levels were significantly higher in both PMW and RMPW with periodontitis, compared to gingivitis or health (p = .0021). Menopause-related changes have no observable effect on GCF levels of TREM-1, PGLYRP1, and IL-1β. Higher GCF TREM-1 levels in women with periodontitis regardless of their menopausal status indicate that TREM-1 may be an indicator for periodontitis both in premenopausal and postmenopausal women.

Association of salivary TREM-1 and PGLYRP1 inflammatory markers with non-communicable diseases.

Triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are elevated in biofluids in the presence of various inflammatory conditions. This cross-sectional study aimed to evaluate the effect of age, sex, smoking and different oral and systemic non-communicable diseases on the levels of TREM-1 and PGLYRP1 in saliva. In total, 445 individuals (mean age 48.7 ± 16.9 years, female:male 51%:49%) were included. All provided self-reported information on smoking and systemic diseases and whole stimulated saliva. Periodontal and cariological parameters were recorded. Salivary levels of TREM-1, PGLYRP1 and total protein were measured using commercially available assays. Salivary TREM-1 levels were significantly higher in stages III-IV periodontitis compared to other periodontal diagnoses (p < .05). Smoking, bleeding on probing (BOP), percentage of pockets ≥4 mm and the number of manifest caries were associated with TREM-1 (p < .05), while sex, BOP, number of manifest caries and muscle and joint diseases were associated with PGLYRP1 (p < .05). Salivary TREM-1 is associated with periodontitis and caries, while PGLYRP1 is associated with gingival inflammation and caries. Additionally, TREM-1 levels are modified by smoking, while PGLYRP1 is modified by sex and muscle and joint diseases. TREM-1 and PGLYRP1 in saliva could serve as potential biomarkers for detecting and monitoring non-communicable diseases.

A phase 1a dose-escalation study of PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on myeloid cells 1).

2523 Background: This study aimed to characterize the safety of PY159 (an agonist antibody to TREM1 that reprograms immunosuppressive intratumoral myeloid cells) as a single agent and in combination with pembrolizumab in subjects with advanced refractory solid tumors, including subjects refractory to immune checkpoint inhibitors. Methods: Two strata were evaluated, PY159 as a single agent and in combination with pembrolizumab, using an accelerated 3+3 dose escalation study design. Dosing was intravenous once every 3 weeks. Disease assessment by RECIST 1.1 was performed every 6 weeks. The single-agent stratum included 7 dose levels of PY159 (range, 0.01–10 mg/kg). The combination stratum included 4 dose levels of PY159 (range, 0.3–10 mg/kg). Pharmacokinetics were evaluated at specified time points. Archival tumor tissue was analyzed for TREM1 expression by immunohistochemistry. Based on preclinical immunohistochemistry data, HR+ HER2– and triple-negative breast cancer, gastric cancer, pancreatic cancer, head and neck cancer, non-small cell lung cancer, and gynecologic cancers were studied. Results: Thirty-seven subjects (median age 65 years; range 29–86 years; 22 female and 15 male) with an ECOG PS &lt;2 were enrolled and all but 5 were RECIST-evaluable (3 withdrew consent, 1 sustained a TEAE, and 1 had a DLT, an asymptomatic grade-3 transaminitis). Twenty subjects received single-agent PY159 and 17 received PY159 in combination with pembrolizumab. Four subjects experienced a grade-3 TRAE, 14 a low-grade immune-related reaction, 18 an SAE (related in 2), and 14 an immune-related adverse event (arthralgias). There were no SUSARs. Five subjects sustained high-grade TRAE resulting in discontinuation. TREM1 levels in the tumors ranged from 0 to 15%. Pharmacokinetic parameters were linear beyond the 0.3 mg/kg dose, dose proportional with a half-life of 8–9 days, and unaffected by pembrolizumab. Radiographic response included 2 partial responses (1 each in an ovarian and pancreatic cancer subject) and stable disease in 9 subjects, ranging from 12 to 96+ weeks. Two subjects continue receiving PY159. Conclusions: PY159 was well tolerated, with an acceptable safety profile, as a single agent and in combination with pembrolizumab. A dose for expansion was derived and enrollment of subjects with 7 prespecified cancers is ongoing. Clinical trial information: NCT04682431 .

Association of peptidoglycan recognition protein 1 to post-myocardial infarction and periodontal inflammation: A subgroup report from the PAROKRANK (Periodontal Disease and the Relation to Myocardial Infarction) study.

Peptidoglycan recognition protein 1 (PGLYRP1) is an antimicrobial and proinflammatory innate immunity protein activated during infections. We aimed to investigate whether PGYLRP1 and associated molecules of the immune response in saliva is a cumulative outcome result of both MI and periodontal inflammation. Two hundred patients with MI and another 200 matched non-MI controls were included. A full-mouthexamination was conducted to assess periodontal inflammation and collection of stimulated saliva was performed 6 to 10weeks after the first MI. PGLYRP1, triggering receptor expressed on myeloid cells 1(TREM-1), interleukin-1 beta (IL-1β) were analyzed by ELISA. Matrix metalloproteinase (MMP)-8 levels were determined by IFMA. Compared to controls, MI patients showed higher salivary PGLYRP1, but not TREM-1 levels. The difference in PGLYRP1 levels remained after adjustment for covariates. In MI patients, the PGLYRP1 levels positively correlated with BOP and PPD 4 to 5mm. Among non-MI subjects, the levels of PGLYRP1 correlated positively and significantly with BOP and total PPD. Salivary PGLYRP1 concentrations also showed strong positive correlations with levels of TREM-1, IL-1β and MMP-8. In multivariate linear regression analysis, in MI patients, BOP and former smokingstatus displayed an association with salivary PGLYRP1 concentration. MI patients showed higher salivary PGLYRP1 levels than healthy controls, also after adjusting for smoking, sex, age and periodontal health status. Salivary levels of PGLYRP1 may reflect the overall inflammatory burden to chronic bacterial exposure, possibly underpinning the observed associations between periodontitis and exposure with MI.

Role of triggering receptor expressed on myeloid cells-1 (TREM-1) in COVID-19 and other viral pneumonias: a systematic review and meta-analysis of clinical studies.

BackgroundTriggering receptor expressed on myeloid cells-1 (TREM-1) has emerged as an important inflammatory marker of immune response associated with severity and mortality outcomes in infection diseases, including viral pneumonias.Aim(1) To evaluate the expression of TREM-1 in patients with COVID-19 and other viral pneumonias compared to healthy individuals; and (2) to analyze the levels of these biomarkers according to disease severity.Materials and methodsThis review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Searches were performed in PubMed, Scopus, Embase, and Google Scholar. Studies were considered eligible if they were observational studies that provided data on the levels of TREM-1 in humans with viral pneumonia compared to healthy controls. The results of the meta-analysis were expressed as standardized mean difference (SMD) and an effect size of 0.8 was considered a large effect. A subgroup analysis was performed according to the disease severity.ResultsSeven studies were included in this systematic review. Four studies included patients with COVID-19 and three analyzed patients with different viruses. The meta-analysis was performed only with patients with COVID-19, which showed increased levels of soluble form of TREM-1 (sTREM-1) among patients with COVID-19 compared to healthy controls (SMD 1.53; 95% CI 0.53–2.52; p < 0.01). No differences were found between patients with mild-to-moderate COVID-19 and healthy controls, but higher levels of sTREM-1 were shown among patients with severe COVID-19 (SMD 1.83; 95% CI 0.77–2.88; p < 0.01). All three studies including patients with other viral pneumonias showed that TREM-1 levels were significantly elevated in infected patients compared with controls.ConclusionThese findings may provide evidence on the pro-inflammatory role of TREM-1 in these infections, contributing to the inflammatory profile and disease progression.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10787-022-00972-6.

Tacrolimus Impairs Kupffer Cell Capacity to Control Bacteremia: Why Transplant Recipients Are Susceptible to Infection.

Kupffer cells (KCs) are the resident intravascular phagocyte population of the liver and critical to the capture and killing of bacteria. Calcineurin/nuclear factor of activated T cells (NFAT) inhibitors (CNIs) such as tacrolimus are used to prevent rejection in solid organ transplant recipients. Although their effect on lymphocytes has been studied extensively, there are limited experimental data about if and how CNIs shape innate immunity, and whether this contributes to the higher rates of infection observed in patients taking CNIs. Here, we investigated the impact of tacrolimus treatment on innate immunity and, more specifically, on the capability of Kupffer cells (KCs) to fight infections. Retrospective analysis of data of >2,700 liver transplant recipients showed that taking calcineurin inhibitors such as tacrolimus significantly increased the likelihood of Staphylococcus aureus infection. Using a mouse model of acute methicillin-resistant S. aureus (MRSA) bacteremia, most bacteria were sequestered in the liver and we found that bacteria were more likely to disseminate and kill the host in tacrolimus-treated mice. Using imaging, we unveiled the mechanism underlying this observation: the reduced capability of KCs to capture, phagocytose, and destroy bacteria in tacrolimus-treated animals. Furthermore, in a gene expression analysis of infected KCs, the triggering receptor expressed on myeloid cells 1 (TREM1) pathway was the one with the most significant down-regulation after tacrolimus treatment. TREM1 inhibition likewise inhibited KC bacteria capture. TREM1 levels on neutrophils as well as the overall neutrophil response after infection were unaffected by tacrolimus treatment. Our results indicate that tacrolimus treatment has a significant impact directly on KCs and on TREM1, thereby compromising their capacity to fend off infections.

Role of TREM-1 in the development of early brain injury after subarachnoid hemorrhage

Triggering receptor expressed on myeloid cells-1 (TREM-1) was found to be induced in the context of subarachnoid hemorrhage (SAH) before. This study further investigates its role in the development of SAH-induced early brain injury (EBI). Firstly, rats were randomly divided into Sham and SAH groups for analysis of temporal patterns and cellular localization of TREM-1. Secondly, TREM-1 intervention was administrated to produce Sham, vehicle, antagonist and agonist groups, for analyzing TREM-1, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and NF-κB expressions at 24 h post-modeling, and EBI assessment at 24 h and 72 h. Thirdly, TLR4 inhibitor (TAK-242) was exploited to produce Sham, Sham+TAK-242, SAH, and SAH + TAK-242 groups to analyze the effects of TLR4 inhibition on TREM-1 induction and EBI evaluation at 72 h. Fourthly, the relationship of soluble TREM-1 (sTREM-1) levels in cerebrospinal fluid of SAH patients with Hunt-Hess grades were explored. The results showed that TREM-1 increased in the brain after experimental SAH (eSAH) early at 6 h and peaked at 48 h, which was found to be located in microglia and endothelial cells. TREM-1 inhibition attenuated EBI associated with TLR4/MyD88/NF-κB suppression, while enhancement had the opposite effects. Contrarily, TLR4 inhibition prevented TREM-1 induction and ameliorated EBI. In addition, sTREM-1 levels in SAH patients positively correlated with Hunt-Hess grades. Overall, the present study provides new evidence that TREM-1 increases dynamically in the brain after eSAH and it is located in microglia and endothelial cells, which may aggravate EBI by interacting with TLR4 pathway. And sTREM-1 in patients might act as a monitoring biomarker of EBI, providing new insights for future studies.

Elevated serum TREM-1 is associated with periodontitis and disease activity in rheumatoid arthritis

The triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are involved in the propagation of inflammatory responses. This study investigated whether serum levels of TREM-1 and PGLYRP1 correlate with periodontitis in rheumatoid arthritis (RA) patients. A total of 154 non-smoking participants with RA (n = 55, F/M: 41/14), Behçet´s disease (BD, n = 41, F/M: 30/11) and healthy controls (HC, n = 58, F/M: 40/18) were recruited. Serum and saliva were collected, the 28-joint disease activity score (DAS-28) was calculated and dental/periodontal measurements were recorded. Serum TREM-1 and PGLYRP1 levels were measured by ELISA and salivary bacterial DNA counts by quantitative polymerase chain reaction. TREM-1 and PGLYRP1 levels were higher in RA (166.3 ± 94.3; 155.5 ± 226.9 pg/ml) than BD (102.3 ± 42.8; 52.5 ± 26.3 pg/ml) and HCs (89.8 ± 55.7; 67.4 ± 37.3 pg/ml) (p < 0.05). In RA, periodontitis was associated with increased TREM-1 and PGLYRP1 levels (p < 0.05), yet in patients under methotrexate TREM-1 levels were lower. TREM-1 correlated with C-reactive protein (CRP) levels, DAS-28 and erythrocyte sedimentation rate, whereas PGLYRP1 positively correlated with CRP. RA patients displayed 3.5-fold higher salivary bacterial DNA counts than HCs. Increased serum TREM-1 levels correlated with PGLYRP1, CRP and DAS-28-ESR in RA patients with periodontitis.

Does iron-deficiency anemia affect M1 macrophage activation and inflammation?

Aim: Iron deficiency anemia (IDA) is a prevalent disorder and may be a problem for various systems. Anemia of inflammation has been extensively investigated before, but there is still a lack of knowledge about macrophage activation in IDA. Hence, the aim of this study was to investigate the relationship between IDA and macrophage activation. Patients and Methods: The present study included 88 female subjects. The participants were divided into two groups: 48 IDA patients in the patient group and 40 healthy subjects in the control group. M1 macrophage activation was measured with the triggering receptor expressed on myeloid cells-1 (TREM-1). TREM-1 levels and C-reactive protein were compared between patient and control groups. The relationship between TREM-1 levels and hemogram parameters and iron status was investigated. Results: TREM-1 levels of the patient group were significantly higher than of the control group [124.5 (6.8-770.5) pg/ml vs 48.5 (0.66-401.1) pg/ml, p=0.02], while CRP levels remained similar between the groups. There was no correlation between TREM-1 levels and hemoglobin, mean erythrocyte volume, ferritin, transferrin saturation and serum iron (p =0.96, 0.14, 0.21, 0.16, and 0.26, respectively) in IDA patients. Conclusion: The present study showed that IDA might increase TREM-1 levels and this condition might be a clue of macrophage activation. IDA patients should be considered in terms of pro-inflammatory conditions and further investigations are needed to clarify the association mentioned above.

Serum Presepsin, Proadrenomedullin and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as Biomarkers for the Diagnosis of Acute Pyelonephritis

To investigate the diagnostic values of serum presepsin, proadrenomedullin (proADM) and triggering receptor expressed on myeloid cells-1 (TREM-1) levels in children with acute pyelonephritis and lower urinary tract infection. Peripheral venous blood and urine samples were obtained before starting antibiotic therapy at the time of admission in all patients. Serum TREM-1, presepsin and proADM concentrations were determined by the enzyme-linked immunosorbent assay method. 82 children (38 acute pyelonephritis, 24 lower urinary tract infection, 20 controls) were enrolled. Serum proADM and TREM-1 levels were higher in patients with acute pyelonephritis than those of lower urinary tract infection and controls (P=0.001 and P<0.001, respectively). Both serum proADM and TREM-1 levels had predictive value for diagnosis of acute pyelonephritis (P=0.006 and P<0.001, respectively). ROC analysis showed that proADM and TREM-1 had positive predictive values for diagnosis of acute pyelonephritis (AUC=0.830, P=0.003; and AUC=0.843, P<0.001, respectively). Serum proADM and TREM-1 levels could serve as early biomarkers for the diagnosis of acute pyelonephritis in children.

SurfaceTREM-1 asa Prognostic Biomarker in Pediatric Sepsis.

To investigate the association between the triggering receptor expressed on myeloid cells-1 (TREM-1) levels and prognosis in septic children. Patients admitted to pediatric intensive care units (PICU) of three tertiary centers were included in this prospective observational study. Serum samples were taken at admission from patients who were hospitalized with sepsis. Of the 87 patients included, 34 (39.1%) had severe sepsis and 53 (60.9%) had septic shock. The median age was 2 y (2 mo to 16 y). TREM-1 values were found to be significantly higher in septic shock patients 129pg/ml (min 9.85- max 494.90) compared to severe sepsis 105pg/ml (min 8.21- max 289.17) (p = 0.048). Despite higher TREM-1 levels been measured in non-survivors compared to survivors, it was not statistically significant [168.98pg/ml (min 9.85- max 494.90) vs. 110.79pg/ml (min 8.21- max 408.90), (p = 0.075)]. Admission TREM-1 levels were higher in septic shock compared to severe sepsis patients. There was no association between mortality and TREM-1 levels in sepsis. TREM-1 measurements should be used carefully in pediatric sepsis prognosis.

Soluble TREM-1 Levels in Familial Mediterranean Fever Related AA-Amyloidosis

ABSTRACT Objectives: Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a monocyte and neutrophil receptor functioning in innate immunity. TREM-1 activity has been studied in various autoimmune diseases such as RA and SLE but there is no data in autoinflammatory pathologies. We studied soluble TREM-1 (sTREM-1) activity in Familial Mediterranean Fever (FMF) cases to evaluate the clinical role of TREM-1 in amyloidosis. Methods: The study includes 62 patients with FMF (42 with amyloidosis) who are regular attendees of a tertiary center for autoinflammatory diseases. For control purposes, 5 patients with AA amyloidosis secondary to other inflammatory diseases, and 20 healthy individuals were also included. Soluble TREM-1 levels were measured using enzyme-linked immunosorbent assay (ELISA). All FMF patients were in an attack-free period during the collection of the blood samples.Results: Soluble TREM-1 levels were found to be significantly higher in the FMF amyloidosis group compared to FMF without amyloidosis group and healthy controls (p = .001 and 0.002). Nevertheless, this difference between sTREM-1 levels was not found among FMF amyloidosis and other AA amyloidosis groups (p = .447) as well as between only FMF patients and healthy controls (p = .532). Soluble TREM-1 levels were found in correlation with creatinine and CRP in the FMF patient group regardless of their amyloidosis diagnosis (r = 0.314, p = .013; r = 0.846, p < .001).Conclusion: TREM-1 seems to be related to renal function rather than disease activity in FMF. Its role as an early diagnostic marker of amyloidosis in FMF complicated with AA amyloidosis should be tested in larger patient groups.

A new inflammatory marker in overweight patients: triggering receptor expressed on myeloid cells-1.

Triggering receptor expressed on myeloid cells 1 (TREM-1) is secreted by phagocytes in adipose tissue and it also upregulates the expression of genes involved in the inflammatory response and atherosclerotic conditions. This study was aimed to investigate the serum TREM-1 levels in overweight patients. Twenty-eight subjects in the overweight group (OG) and 20 age-matched healthy subjects in the control group (CG) (BMI 27.6±1.2 vs 23.1±2.17 kg/m2, respectively, p<0.001) were included in the study. The serum sTREM-1 level was measured by ELISA. The homeostasis model assessment score (HOMA-IR) was also calculated. The mean TREM-1 levels were significantly higher in OG than in CG (407.3±323.7 vs 150.3±152.7 pg/mL, respectively, p<0.001). The HOMA-IR score was also significantly higher in OG than in CG (3.42±3.63 vs 2.77±1.61, respectively). A positive correlation was detected between TREM-1 and BMI (r=0.318, p=0.028). This study mainly demonstrated that a high serum TREM-1 level might be an early inflammatory marker in overweight patients. We found that TREM-1 might be associated with BMI in overweight patients regardless of insulin resistance (Tab. 1, Ref. 21). Text in PDF www.elis.sk.

Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as a New Marker in Ventilated Children with Pneumonia

Pneumonia is the world's leading infectious cause of mortality. This is one of the most common lower respiratory tract infections, which contributes significantly to the burden of antibiotic use. Because of the complexity of the pathophysiology, pneumonia is widely recognized that the clinical diagnosis and prognosis are usually not enough to accurately estimate the severity of the condition. The most difficult task for a doctor is above all the value of risk in patients with community-acquired pneumonia. Early diagnosis is important to reduce hospitalization and death. There are widespread biomarkers, none of which look perfect, and the demand for new biomarkers that maximizes the severity and treatment response for pneumonia has increased lately. Ventilation-related pneumonia (VAP) is a hospital-acquired pneumonia that can occur more than 48 hours after mechanical ventilation. This is a common complication of mechanical ventilation, which has a high mortality rate. VAP can make it difficult for patients to turn off the ventilator and cause longer hospitalizations, which can cause a very large financial burden for patients and the need for large medical resources. The incidence and mortality of VAP have decreased with the progress of prevention strategies in the last few decades. However, VAP is still one of the most common causes of nosocomial infections and a frequent cause of death in intensive care units. Current challenges in VAP treatment include the lack of a gold standard for diagnosis, the lack of effective prevention strategies, and increased antibiotic resistance. Active receptors are expressed on myeloid cells (TREM-1) and are considered to be glycoprotein members of the immunoglobulin family. TREM-1 is an inflammatory receptor that causes inflammation after exposure to extracellular fungi and bacterial pathogens. Elevated TREM-1 levels are a potential marker of lung disease. The aim of this study is to evaluate sTREM-1 levels in the serum of pneumonia patients and their use as new biomarkers, which seem promising for accurate diagnosis, risk and follow-up of VAP, always, however, one of the most common causes is nosocomial infection and one of the leading causes of death most commonly in intensive care units. A comparative study was conducted on children diagnosed with pneumonia admitted to Pediatric Abo El Rish Intensive Care Unit and Abo El Rish Pediatric Hospital, Cairo University, compared to age and sex-matched healthy control group. sTREM-1 level was measured using ELISA technique while CRP by Nephelometry. TREM-1 level was significantly higher in ventilated children with pneumonia compared to the control group. No significant correlation was found between sTREM-1 level and CRP level in the studied children. TREM-1 is not a pulmonary infection marker only but a reliable marker for ventilator-associated pneumonia (VAP).

Regulation of Salivary Peptidoglycan Recognition Protein 1 in Adolescents.

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. 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. 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). 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. 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. 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.

A point-of-care test of active matrix metalloproteinase-8 predicts triggering receptor expressed on myeloid cells-1 (TREM-1) levels in saliva.

This cross-sectional study aims to investigate if a point-of-care (PoC) test of active matrix metalloproteinase-8 (aMMP-8) predicts levels of inflammation amplifier triggering receptor expressed on myeloid cells-1 (TREM-1) and its putative ligand the neutrophil peptidoglycan recognition protein 1 (PGLYRP1) in saliva. Forty-seven adolescents, aged 15 to 17 years, were tested with aMMP-8 PoC test, which was followed by a full-mouth clinical examination of the assessment of periodontal, mucosal, and oral health. TREM-1 and PGLYRP1 levels were analyzed by ELISA. The immunofluorometric assay (IFMA) specific for aMMP-8 was used as the reference method. Fourteen saliva samples out of a total of 47 showed positivity for aMMP-8 PoC test. Both the TREM-1 and the aMMP-8 (IFMA) levels were significantly elevated among the aMMP-8 PoC test positives compared with the PoC test negatives (P<0.05). Moreover, aMMP-8 levels assessed by IFMA showed a strong positive correlation with TREM-1 levels in saliva (r = 0.777, P<0.001). The number of sites with a probing depth of ≥4 mm was significantly lower among the adolescents that had a negative aMMP-8 PoC test result, and TREM-1 levels < 75pg/mL (P< 0.05). In contrast, adolescents with a positive aMMP-8 PoC test result (i.e., elevated aMMP-8 levels) together with elevated TREM-1 levels had a significantly higher number of periodontal pockets with ≥4 mm (P < 0.001). The present study validated usability of aMMP-8 PoC test for predicting "proinflammatory" salivary profile and periodontal health status in adolescents.

Role of TREM-1 in pulmonary tuberculosis patients- analysis of serum soluble TREM-1 levels

Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory responses and is upregulated during sepsis and pulmonary infection. The association between serum soluble TREM-1 (sTREM-1) level and pulmonary tuberculosis (PTB) disease deserves investigation. In the present study, patients with PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects were prospectively enrolled and serum levels of sTREM-1, sTREM-2, and C-reactive protein (CRP) were measured. We correlated serum biomarkers and clinical presentations and treatment outcomes of PTB cases. We also utilized immunohistochemistry (IHC) to visualize TREM-1-expressing cells in lung tissues from PTB patients. A total of 86 PTB, 41 LTBI, and 20 non-TB, non-LTBI subjects were enrolled. Serum levels of sTREM-1 and CRP significantly increased in PTB patients; these higher serum levels were correlated with more advanced involvement in chest films and higher bacteria burden in sputum. In multivariate analysis, serum levels of sTREM-1 >260 pg/mL and CRP >2.6 mg/L were independent predictors for on-treatment mortality. Abundant TREM-1-expressing macrophages were identified in lung tissues from PTB samples. In conclusion, serum levels of sTREM-1 correlated with disease severity and treatment outcomes in PTB patients.

TREM1 intervention does not affect renal pathology upon ischemia/reperfusion injury (TRAN1P.929)

Abstract Rationale:Following transplantation, renal ischemia is a major cause of Acute Kidney injury(AKI). TREM1(Triggering receptor expressed on myeloid cells 1) is an innate immune receptor expressed on neutrophils and monocytes/macrophages, the most common cells infiltrating the kidney upon IR. TREM1 enhances Toll-like receptor (TLR)-induced inflammatory response in several models of infection and sterile inflammation.TREM1 inhibition reduced disease severity in mesenteric ischemia-reperfusion induced injury (IRI).We hypothesized that TREM1 intervention will also reduce renal IRI. Methods:Mice were subjected to renal IRI induced by occlusion of the renal artery for 25’ and reperfused for 24h. Mice were treated i.p. with different doses of LP17, LR12, TREM1 fusion protein and control peptides.Renal TREM1 protein expression and plasma sTREM1 were measured. TREM1 expression on circulating granulocyte and monocyte, renal function (creatinine, urea), damage (PASD) and inflammation (KC and LY6G-positive cell infiltration) were evaluated. Results:IRI was associated with increased renal and circulating TREM1 protein levels. TREM1 levels were similar on circulating granulocyte but decrease on monocyte upon IR. TREM1 intervention with LP17, LR12 and TREM1 fusion protein did not reduce renal dysfunction, injury or inflammation following IRI. Conclusion: The modulation of the TREM-1 pathway by means of synthetic peptides and fusion protein does not represent a useful tool to prevent renal IRI.

TREM-1 expression in rat corneal epithelium with Aspergillus fumigatus infection.

To investigate the expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in the aberrant inflammation within the corneal epithelium at early period of fungal infection. A total of 65 Wistar rats were randomly divided into control group, sham group and fungal keratitis (FK) group, in which the cornea was infected by Aspergillus fumigatus (A. fumigatus). After executed randomly at 8, 16, 24, 48 and 72h after experimental model being established, the severity of keratomycosis in rats was scored visually with the aid of a dissecting microscope and slit lamp. Then corneas in three groups were collected to assess the expression of TREM-1 through quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence technique and Western blot analysis. The correlation between FK inflammation and expression of TREM-1 was also analyzed. Corneal inflammation scores increased with time after fungal infection (F=49.74, P=0.000). The inflammation scores in FK group were obviously higher than those in sham group on the whole (F=137.78, P=0.000). Levels of TREM-1 in the infected rat corneal epithelium had elevated at 8h and peaked at 48h (P<0.001, compared with control group). Western blot analysis also showed an obviously elevated TREM-1 level in rat corneal epithelium at 24h and 48h after fungal infection. Immunofluorescencetechnique showed that TREM-1 mainly existed in corneal epithelium and infected corneal stoma of rat. TREM-1 protein expression was enhanced after fungal infection. Moreover, severity of FK inflammation was significantly related to TREM-1 expression in FK (r=0.942, P=0.000). TREM-1 may contribute to amplify the inflammation in the cornea infected with A. fumigatus and play critical roles in the battle against A. fumigatus in the innate immune responses.

TREM-1 and Pentraxin-3 Plasma Levels and Their Association with Obstructive Sleep Apnea, Obesity, and Endothelial Function in Children

Obstructive sleep apnea (OSA) is a common health problem in children and increases the risk of cardiovascular disease (CVD). Triggering receptor expressed on myeloid cells-1 (TREM-1) plays an important role in innate immunity and amplifies inflammatory responses. Pentraxin-3 is predominantly released from macrophages and vascular endothelial cells, plays an important role in atherogenesis, and has emerged as a biomarker of CVD risk. Thus, we hypothesized that plasma TREM-1 and pentraxin-3 levels would be elevated in children with OSA. ONE HUNDRED SIX CHILDREN (MEAN AGE: 8.3 ± 1.6 y) were included after they underwent overnight polysomnographic evaluation and a fasting blood sample was drawn the morning after the sleep study. Endothelial function was assessed with a modified hyperemic test after cuff-induced occlusion of the brachial artery. Plasma TREM-1 and pentraxin-3 levels were assayed using commercial enzyme-linked immunosorbent assay kits. Circulating microparticles (MPs) were assessed using flow cytometry after staining with cell-specific antibodies. Children with OSA had significantly higher TREM-1 and pentraxin-3 levels (versus controls: P < 0.01, P < 0.05, respectively). Plasma TREM-1 was significantly correlated with both body mass index (BMI)-z score and the obstructive apnea-hypopnea index (AHI) in univariate models. Pentraxin-3 levels were inversely correlated with BMI-z score (r = -0.245, P < 0.01), and positively associated with endothelial MPs and platelet MPs (r = 0.230, P < 0.01 and r = 0.302, P < 0.01). Both plasma TREM-1 and pentraxin-3 levels were independently associated with AHI in multivariate models after controlling for age, sex, race, and BMI-z score (P < 0.001 for TREM-1 and P < 0.001 for pentraxin-3). However, no significant associations emerged between TREM-1, pentraxin-3, and endothelial function. Plasma TREM-1 and pentraxin-3 levels are elevated in pediatric OSA, and may play a role in modulating the degree of systemic inflammation. The short-term and long-term significance of elevated TREM-1 and pentraxin-3 in OSA-induced end-organ morbidity remains to be defined.