TREM-1 Research Articles

Resveratrol attenuates the pathogenic and inflammatory properties of Porphyromonas gingivalis

Porphyromonas gingivalis has been strongly associated with chronic periodontitis, which affects tooth-supporting tissues. This Gram-negative anaerobic bacterium produces a repertoire of virulence factors that modulate tissue destruction directly or indirectly by the induction of inflammatory processes. The aim of this study was to investigate the effects of resveratrol, a major polyphenol found in grapes and wine, on the growth and virulence properties of P.gingivalis as well as on gingival keratinocyte tight junction integrity and the host inflammatory response. Resveratrol exhibited antibacterial activity that may result from damage to the bacterial cell membrane. Resveratrol also killed a pre-formed P.gingivalis biofilm and reduced bacterial adherence to matrix proteins. In addition, resveratrol had a protective effect on the integrity of the keratinocyte tight junctions by inhibiting its breakdown by P.gingivalis. This may be related to the ability of resveratrol to inhibit the protease activities of P.gingivalis. Lastly, resveratrol reduced P.gingivalis-mediated activation of the NF-κB signaling pathway and attenuated TREM-1 gene expression as well as soluble TREM-1 secretion in monocytes. The effect on NF-κB activation likely results from the ability of resveratrol to act as a PPAR-γ agonist. In summary, the antibacterial, anti-adherence, and antiprotease properties of resveratrol, as well as its ability to protect the gingival keratinocyte barrier and attenuate the inflammatory response in monocytes suggest that it may be a promising novel therapeutic agent for treating periodontal disease.

Lack of an Association between the Functional Polymorphism TREM-1 rs2234237 and the Clinical Course of Sepsis among Critically Ill Caucasian Patients-A Monocentric Prospective Genetic Association Study.

Sepsis is a life-threatening condition and a significant challenge for those working in intensive care, where it remains one of the leading causes of mortality. According to the sepsis-3 definition, sepsis is characterized by dysregulation of the host response to infection. The TREM-1 gene codes for the triggering receptor expressed on myeloid cells 1, which is part of the pro-inflammatory response of the immune system. This study aimed to determine whether the functional TREM-1 rs2234237 single nucleotide polymorphism was associated with mortality in a cohort of 649 Caucasian patients with sepsis. The 90-day mortality rate was the primary outcome, and disease severity and microbiological findings were analyzed as secondary endpoints. TREM-1 rs2234237 TT homozygous patients were compared to A-allele carriers for this purpose. Kaplan–Meier survival analysis revealed no association between the clinically relevant TREM-1 rs2234237 single nucleotide polymorphism and the 90-day or 28-day survival rate in this group of septic patients. In addition, the performed analyses of disease severity and the microbiological findings did not show significant differences between the TREM-1 rs2234237 genotypes. The TREM-1 rs2234237 genotype was not significantly associated with sepsis mortality and sepsis disease severity. Therefore, it was not a valuable prognostic marker for the survival of septic patients in the studied cohort.

TREM-1 Attenuates RIPK3-mediated Necroptosis in Hyperoxia-induced Lung Injury in Neonatal Mice.

Hyperoxia-induced injury to the developing lung, impaired alveolarization, and dysregulated vascularization are critical factors in the pathogenesis of bronchopulmonary dysplasia (BPD); however, mechanisms for hyperoxia-induced development of BPD are not fully known. In this study, we show that TREM-1 (triggering receptor expressed on myeloid cells 1) is upregulated in hyperoxia-exposed neonatal murine lungs as well as in tracheal aspirates and lungs of human neonates with respiratory distress syndrome and BPD as an adaptive response to survival in hyperoxia. Inhibition of TREM-1 function using an siRNA approach or deletion of the Trem1 gene in mice showed enhanced lung inflammation, alveolar damage, and mortality of hyperoxia-exposed neonatal mice. The treatment of hyperoxia-exposed neonatal mice with agonistic TREM-1 antibody decreased lung inflammation, improved alveolarization, and was associated with diminished necroptosis-regulating protein RIPK3 (receptor-interacting protein kinase 3). Mechanistically, we show that TREM-1 activation alleviates lung inflammation and improves alveolarization through downregulating RIPK3-mediated necroptosis and NLRP3 (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3) inflammasome activation in hyperoxia-exposed neonatal mice. These data show that activating TREM-1, enhancing angiopoietin 1 signaling, or blocking the RIPK3-mediated necroptosis pathway may be used in new therapeutic interventions to control adverse effects of hyperoxia in the development of BPD.

Relationship between triggering receptor expressed on myeloid cells and postoperative cognitive dysfunction in elderly patients

Objective To evaluate the relationship between the triggering receptor expressed on myeloid cells (TREM) and postoperative cognitive dysfunction (POCD) in elderly patients. Methods Eighty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients, aged 65-85 yr, weighing 50-80 kg, scheduled for elective total knee replacement under spinal-epidural anesthesia were enrolled in this study.Cerebrospinal fluid (CSF) was extracted after a catheter was successfully inserted into subarachnoid space.Blood samples from the cubital vein was collected before anesthesia induction (T0) and at 24 and 72 h after surgery (T1, 2). The concentrations of TREM1 and TREM2 in CSF and plasma and tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in plasma were measured by enzyme-linked immunosorbent assay.The expression of TREM1, TREM2, IL-6 and TNF-α protein and mRNA in mononuclear cells in peripheral blood was detected using real-time polymerase chain reaction.Neuropsychological test was performed in the the same time period at 1 day before surgery and 7 days after surgery, and the Z score was used to diagnose the development of POCD.The patients were divided into POCD group (P group) and non-POCD group (NP group) according to whether or not POCD happened after surgery. Results The incidence of POCD was 22%.Compared with group NP, the plasma TREM1 concentrations at T1, 2 and plasma IL-6 and TNF-α concentrations at T2 were significantly increased, and the expression of TREM1 mRNA and TNF-α mRNA at T1, 2 and IL-6 mRNA at T2 was up-regulated in group P (P 0.05). There was a higher consistency between plasma and CSF TREM1 concentrations (Cronbach′s Alpha=0.784, P<0.01) and a high consistency between plasma and CSF TREM2 (Cronbach′s Alpha=0.935, P<0.01). Conclusion Up-regulated expression of central and peripheral TREM1 is related to the development of POCD in elderly patients. Key words: Aged; Congnition disorders; Myeloid cells; Receptors, immunologic

Nuclear receptor ligands induce TREM-1 expression on dendritic cells: analysis of their role in tumors

ABSTRACTDendritic cells (DCs) initiate adaptive immune responses after their migration to secondary lymphoid organs. The LXR ligands/oxysterols and the RXR ligand 9-cis Retinoic Acid (9-cis RA) were shown to dampen DC migration to lymphoid organs through the inhibition of CCR7 expression. We performed transcriptomics of DCs undergoing maturation in the presence of the LXR ligand 22R-Hydroxycholesterol (22R-HC). The analysis highlighted more than 1500 genes modulated by 22R-HC treatment, including the triggering receptor expressed on myeloid cells (TREM)-1, which was found markedly up-regulated. We tested the effect of other nuclear receptor ligands (NRL) and we reported the induction of TREM-1 following RXR, RAR and VDR activation. From a functional point of view, triggering of TREM-1 induced by retinoids increased TNFα and IL-1β release, suggesting an active role of NRL-activated TREM-1+ DCs in inflammation-driven diseases, including cancer. Consistently with this hypothesis we detected DCs expressing TREM-1 in pleural effusions and ascites of cancer patients, an observation validated by the induction of TREM-1, LXR and RAR target genes when monocyte-DCs were activated in the presence of tumor-conditioned fluids. Finally, we observed a better control of LLC tumor growth in Trem-1−/- bone marrow chimera mice as compared to wild type chimera mice. Future studies will be necessary to shed light on the mechanism of TREM-1 induction by distinct NRL, and to characterize the role of TREM-1+ DCs in tumor growth.

The expression of TREMs in ischemic optic neuropathy of rats

Objective To investigate the expression of TREMs and the related pathway in ischemic optic neuropathy (ION) of rats. Methods The permanent ligation of bilateral internal carotid arteries (BICA) of rat was performed for 14 days to establish sub-acute ION model as model group. The control group were separated BICA without ligation. The expression of TREM-1, TREM-2, Caspase-3 and IL-6 genes and proteins were detected by reverse transcription PCR(RT-PCR) and Western Blot, respectively. Results Compared with control group, the expressions of TREM-1, Caspase-3 and IL-6 in model group were higher and TREM-2 was lower (P=0.001). Conclusion TREM-1 has effects on inducing apoptosis and inflammation. Reversely, TREM-2 shows opposite effects. Key words: Optic neuropathy, ischemic; TREM-1; TREM-2; Caspase-3; IL-6

Pravastatin improves atherosclerosis in mice with hyperlipidemia by inhibiting TREM-1/DAP12.

To study the protective effect of pravastatin on blood vessels in mice with hyperlipemia. Apolipoprotein E (ApoE)-/- and triggering receptor expressed on myeloid (TREM)-/ApoE-/- mice were selected and fed with high-fat food, which were then subdivided into the control group and the pravastatin intervention group. C57BL/6J mice were used as controls. Oil Red O staining was used to stain aortas and sections so as to observe the level and basic composition of plaques. Immunohistochemistry was applied to detect inflammatory cells expression in aortic plaques. Real-time polymerase chain reaction (PCR) was employed to detect the expressions of TREM-1, tumor necrosis factor-alpha (TNF-α), and interleukin-1 (IL-1) messenger ribonucleic acids (mRNAs) in vascular tissues of mice in different groups, and the expressions of TREM-1, DNAX-activating protein of molecular mass 12 (DAP12), TNF-α, and IL-1 were detected via Western blotting technique. Pravastatin reduced the area of atherosclerotic plaques and improved the plaque formation by reducing lipid deposits and alleviating plaque inflammatory responses. In the pravastatin group, the expression of TREM-1 in the aorta atherosclerotic plaque of mice was decreased, the expressions of TREM-1 and DAP12 genes and proteins in vascular tissue cells declined, and the expressions of the downstream inflammatory factors, TNF-α, IL-1 were reduced. Pravastatin improves atherosclerosis (AS) in mice by inhibiting TREM-1/DAP12.

Relationship between TREM-1 gene polymorphism and susceptibility to coronary atherosclerotic heart disease

Objective To explore the relationship between gene polymorphisms of triggering receptor expressed on myeloid cells-1 (TREM-1) rs2234237A/T, rs9471535A/G and susceptibility to coronary atherosclerotic heart disease(coronary heart disease for short, CHD). Methods A case-control study. 120 patients with CHD (CHD group) and 90 healthy people (Normal control group) were selected from November 2016 to April 2017 in Jingzhou Central Hospital. The single nucleotide polymorphisms(SNPs) of TREM-1gene (rs2234237 and rs9471535)were analyzed using Sanger method in all subjects. Comparing baseline clinical data and the distribution of genotype frequencies in the two groups. Non conditional logistic regression was used to analyze the relationship between TREM-1 gene ( rs2234237 and rs9471535) polymorphisms and susceptibility to CHD. Results The proportion of gender as well as level of age, body mass index, total cholesterol, triglyceride and low density lipoprotein cholesterol were not statistically significant between the two groups(χ2 =0.575, P>0.05; t=-1.670, P>0.05; t=-1.719, P>0.05; t=1.011, P>0.05; t=-1.834, P>0.05; t=0.474, P>0.05, respectively), while the proportion of smoking, hypertension and diabetes as well as level of high density lipoprotein cholesterol and fasting plasma glucose were statistically significant between the two groups (χ2 =4.321, P 0.05). Conclusions TREM-1 gene rs2234237 A/T and rs9471535 A/G polymorphisms are significantly associated with susceptibility to CHD . rs2234237 TT genotype and rs9471535 GG genotype might act as protective factors of CHD.(Chin J Lab Med, 2018, 41: 436-441) Key words: Coronary disease; Triggering receptor expressed on myeloid cells-1; Polymorphism, single nucleotide; Disease susceptibility

AmpliSeq transcriptome analysis of human alveolar and monocyte-derived macrophages over time in response to Mycobacterium tuberculosis infection.

Human alveolar macrophages (HAM) are primary bacterial niche and immune response cells during Mycobacterium tuberculosis (M.tb) infection, and human blood monocyte-derived macrophages (MDM) are a model for investigating M.tb-macrophage interactions. Here, we use a targeted RNA-Seq method to measure transcriptome-wide changes in RNA expression patterns of freshly obtained HAM (used within 6 h) and 6 day cultured MDM upon M.tb infection over time (2, 24 and 72 h), in both uninfected and infected cells from three donors each. The Ion AmpliSeq™ Transcriptome Human Gene Expression Kit (AmpliSeq) uses primers targeting 18,574 mRNAs and 2,228 non-coding RNAs (ncRNAs) for a total of 20,802 transcripts. AmpliSeqTM yields highly precise and reproducible gene expression profiles (R2 >0.99). Taking advantage of AmpliSeq’s reproducibility, we establish well-defined quantitative RNA expression patterns of HAM versus MDM, including significant M.tb-inducible genes, in networks and pathways that differ in part between MDM and HAM. A similar number of expressed genes are detected at all time-points between uninfected MDM and HAM, in common pathways including inflammatory and immune functions, but canonical pathway differences also exist. In particular, at 2 h, multiple genes relevant to the immune response are preferentially expressed in either uninfected HAM or MDM, while the HAM RNA profiles approximate MDM profiles over time in culture, highlighting the unique RNA expression profile of freshly obtained HAM. MDM demonstrate a greater transcriptional response than HAM upon M.tb infection, with 2 to >10 times more genes up- or down-regulated. The results identify key genes involved in cellular responses to M.tb in two different human macrophage types. Follow-up bioinformatics analysis indicates that approximately 30% of response genes have expression quantitative trait loci (eQTLs in GTEx), common DNA variants that can influence host gene expression susceptibility or resistance to M.tb, illustrated with the TREM1 gene cluster and IL-10.

High mobility group box 1 protein in bronchoalveolar lavage fluid and correlation with other inflammatory markers in pulmonary diseases.

Objectives: Analysis of new markers in bronchoalveolar lavage fluid (BALF) provides new insights into the immunopathogenesis and may be helpful in differential diagnosis of lung diseases. High mobility group box 1 protein (HMGB1) is a non-histone nuclear protein and its release into the extracellular environment may be associated with the inflammatory response. The aim of the study is the analysis of HMGB1 in BALF, correlations with other markers of inflammation and differences in extracellular HMGB1 levels in various lung diagnoses. Methods: The concentration of HMGB1 was tested by an Elisa test. We calculated correlations with other inflammatory markers (leukocytes, total protein, albumin, IgG, IgA, IgM, C3 complement component, alpha-2macroglobuline, CD3, CD4, CD8, TREM-1 and TREM-2) and specified HMGB1 level in various diagnoses. Results: A positive correlation was found between the level of HMGB1 and total protein levels (p=0.0001), albumin (p=0.0058), IgA (p=0.011), IgM (0.0439) and TREM-2 (p=0.0188). Conversely, a negative correlation was revealed between HMGB1 and TREM-1 (p=0.0009). HMGB1 level varied in different diagnoses: the highest level was detected in QuantiFERON TB-positive subjects (median: 30.2) and hypersensitivity pneumonitis (median: 33.2), followed by pulmonary sarcoidosis (median: 16.8) and idiopathic pulmonary fibrosis (median: 8.8). Conclusion: HMGB1 correlates with other inflammatory markers tested in BALF. Its level varies in different lung diagnoses. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 268-275).

Leishmania infantum Induces the Release of sTREM-1 in Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to be a major global health problem. The inflammatory response during VL is characterized by the release of several cytokines and other pro-inflammatory mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of evolutionarily conserved membrane-bound surface receptors expressed on neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling events that drive cytokine production, degranulation, and phagocytosis. In certain inflammatory-associated diseases, TREM-1 can also be found as a soluble form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these studies, we now find that high levels of circulating sTREM-1 correlate directly with VL disease severity. In particular, high levels of sTREM-1 were observed in non-survivor VL patients. Furthermore, these levels of sTREM-1 positively correlated with liver size and negatively correlated with leukocyte counts and hemoglobin concentration. Moreover, we found that neutrophils exposure in vitro to Leishmania infantum modulates TREM-1, DAP12, and IL-8 gene expression, while also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1 levels are associated with increasing parasite ratio. Taken together, these studies suggest that L. infantum may modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL.

Diagnostic value of soluble triggering receptor expressed on myeloid cells-1 in pleural effusion

Objectives The aim of this study was to assess the value of the pleural fluid soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the diagnosis of the etiology of pleural effusion. Background The accurate diagnosis of pleural effusion remains a challenging problem even after thoracocentesis and closed pleural biopsy. TREM-1 is a recently described molecule that plays an important role in myeloid cell-activated inflammatory responses. Patients and methods We measured sTREM-1 levels from 20 patients with transudative effusion, 20 patients with malignant effusion, 20 patients with tuberculous effusion, and 20 patients with parapneumonic effusion using a specific enzyme-linked immunosorbent assay technique. Result sTREM-1 levels were significantly higher in parapneumonic effusion (45.50 ± 13.21 ng/l) than tuberculous effusion (34.90 ± 10.51 ng/l) and in malignant effusion (15.37 ± 5.01 ng/l) than transudative effusion (6.75 ± 3.35 ng/l). Conclusion Our study suggests that sTREM-1 can differentiate between infectious effusions (parapneumonic and tuberculous) and noninfectious effusions (malignant and transudative effusions).

Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB

The triggering receptor expressed on myeloid cells (TREM) family of proteins are cell surface receptors with important roles in regulation of myeloid cell inflammatory activity. In the central nervous system, TREM2 is implicated in further roles in microglial homeostasis, neuroinflammation and neurodegeneration. Different TREM receptors appear to have contrasting roles in controlling myeloid immune activity therefore the relative and co-ordinated regulation of their expression is important to understand but is currently poorly understood. We sought to determine how microglial TREM expression is affected under neuroinflammatory conditions in vitro and in vivo. Our data show that microglial Trem1 and Trem2 gene expression are regulated in an opposing manner by lipopolysaccharide (LPS) in vitro in both adult murine and human microglia. LPS caused a significant induction of Trem1 and a contrasting suppression of Trem2 expression. We also observed similar divergent Trem1 and Trem2 responses in vivo in response to acute brain inflammation and acute cerebral ischaemia. Our data show that inhibition of NF-κB activation prevents the LPS-induced alterations in both Trem1 and Trem2 expression in vitro indicating NF-κB as a common signaling intermediate controlling these divergent responses. Distinct patterns of microglial Trem1 induction and Trem2 suppression to different Toll-like receptor (TLR) ligands were also evident, notably with Trem1 induction restricted to those ligands activating TLRs signaling via TRIF. Our data show co-ordinated but divergent regulation of microglial TREM receptor expression with a central role for NF-κB. Neuroinflammatory conditions that alter the balance in TREM expression could therefore be an important influence on microglial inflammatory and homeostatic activity with implications for neuroinflammatory and neurodegenerative disease.

IMPACT OF INNATE IMMUNITY GENES IN DEVELOPMENT OF CRITICAL POSTOPERATIVE COMPLICATIONS AFTER CORONARY ARTERY BYPASSES GRAFTING

Introduction. Postoperative critical complications after coronary artery bypass grafting are the result of innate immunity functioning that related with individual features and sometimes genetically determined. The aim: to evaluate the contribution of innate immunity genes polymorphisms in the development of critical postoperative complications of coronary artery bypass grafting. Design and methods: 680 patients with coronary artery disease after coronary artery bypass grafting were involved in the investigation. TREM-1 and TLR genes polymorph loci were genotyped using allele-specifi c real-time PCR. Results. It was found that allele G rs1817537 (OR = 2,94 (95%CI = 1,09-7,92); р = 0,019), allele Т rs2234246 (OR = 3,64 (95%CI = 1,24-10,73); р = 0,0076) and allele Т rs3804277 (OR = 2,94 (95%CI = 1,09-7,92); р = 0,019) of TREM-1 gene are associated with high risk of multiple organ failure while allele C rs3775073 TLR6 (OR = 0,33 (95%CI = 0,15-0,71); р = 0,0045), allele А rs7768162 TREM-1 (OR = 0,46 (95%CI = 0,21-0,98); р = 0,043) and T/T genotype of rs4711668 TREM-1 (OR = 0,22 (95%CI = 0,05-0,97); р = 0,015) are associated with decreased risk. Conclusion. Rare alleles in some polymorphic sites of innate immunity genes demonstrate the importance in multiple organ failure development.

Triggering Receptor Expressed on Myeloid cells-1: a new player in platelet aggregation.

Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is an immunoreceptor initially known to be expressed on neutrophils and monocytes/macrophages. TREM-1 acts as an amplifier of the inflammatory response during both infectious and aseptic inflammatory diseases. Another member of the TREM family, The Triggering receptor expressed on myeloid cells Like Transcript-1 (TLT-1) is exclusively expressed in platelets and promotes platelet aggregation. As the gene that encodes for TLT-1 is located in the TREM-1 gene cluster, this prompted us to investigate the expression of TREM-1 on platelets. Here we show that TREM-1 is constitutively expressed in α-granules and mobilised at the membrane upon platelet activation. Pharmacologic inhibition of TREM-1 reduces platelet activation as well as platelet aggregation induced by collagen, ADP, and thrombin in human platelets. Aggregation is similarly impaired in platelets from Trem-1-/- mice. In vivo, TREM-1 inhibition decreases thrombus formation in a carotid artery model of thrombosis and protects mice during pulmonary embolism without excessive bleeding. These findings suggest that TREM-1 inhibition could be useful adducts in antiplatelet therapies.

Effect of TREM-1 blockade and single nucleotide variants in experimental renal injury and kidney transplantation.

Renal ischemia reperfusion (IR)-injury induces activation of innate immune response which sustains renal injury and contributes to the development of delayed graft function (DGF). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pro-inflammatory evolutionary conserved pattern recognition receptor expressed on a variety of innate immune cells. TREM-1 expression increases following acute and chronic renal injury. However, the function of TREM-1 in renal IR is still unclear. Here, we investigated expression and function of TREM-1 in a murine model of renal IR using different TREM-1 inhibitors: LP17, LR12 and TREM-1 fusion protein. In a human study, we analyzed the association of non-synonymous single nucleotide variants in the TREM1 gene in a cohort comprising 1263 matching donors and recipients with post-transplant outcomes, including DGF. Our findings demonstrated that, following murine IR, renal TREM-1 expression increased due to the influx of Trem1 mRNA expressing cells detected by in situ hybridization. However, TREM-1 interventions by means of LP17, LR12 and TREM-1 fusion protein did not ameliorate IR-induced injury. In the human renal transplant cohort, donor and recipient TREM1 gene variant p.Thr25Ser was not associated with DGF, nor with biopsy-proven rejection or death-censored graft failure. We conclude that TREM-1 does not play a major role during experimental renal IR and after kidney transplantation.

The Role of TREM-1 Gene Expression and Soluble TREM-1 as Prognostic Markers of Sepsis

Background: Determination of TREM-1 expression on monocytes has been investigated as a perspective diagnostic method to distinguish infectious from non-infectious etiology of the inflammation. Objectives: To analyse the expression of the TREM-1 gene in patients of sepsis and septic shock and its relation with the severity of pathophysiological conditions. Also to describe the dynamics changes of soluble TREM- 1, procalcitonin and C-reactive protein during the course of sepsis and Correlation between their expressions and the clinical scoring system known as APACHE II scoring system. Material and Methods: After an ethical approval, the expression of mRNA of TREM-1 in PMNs was detected in 76 critically ill patients (49 with sepsis and 27 with septic shock) were analyzed by using quantitative real-time PCR. The concentration of s. TREM-1, CRP and PCT levels were measured by an enzyme immunoassay. Results: On the ICU admission, the septic shock group displayed higher levels of sTREM-1, PCT, APACHE II score (P<0.001) and CRP (P=0.01) than the sepsis group. Significant positive correlation (P<0.05) between APACHE II and both sTREM-1 and PCT in the prognosis of morbidity were shown. The mRNA levels of patients suffering from sepsis and septic shock were 0.54- and 0.39-fold lower compared to those of healthy subjects (1.06) respectively. Conclusion: With regard to sepsis diagnosis and severity, sTREM-1 and PCT have positive values in prognostic assessment of the disease and may be taken as a survival-impacting risk factor. The TREM-1 gene expression levels isolated from patients with sepsis may be used as a surrogate marker for determining the severity.

The effect of signal transduction pathway of triggering receptor-1 expressed on myeloid cells in acute lung injury induced by paraquat in rats

To investigate the transduction pathway of triggering receptor-1 expressed on myeloid cells (TREM-1) in acute lung injure induced by paraquat in rats through the activating or blocking TREM-1, to observe the effect of signal transduction pathway in the acute lung injure induced-paraquat. 80 SD rats were randomly divided into normal saline control group (n=20) , PQ poisoning group (n=20) , antibody group (n=20) , and LP17 group (n=20). poisoning group, antibody group and LP17 group were given saline diluting PQ 80 mg/kg of disposable lavage after 2 h, a single set of intraperitoneal injection of anti-TREM-1 mAb (250 g/kg) , tail intravenous LP17 group synthetic peptide (3.5 mg/kg) , poisoning group was given equal normal saline intraperitoneal injection, control group given normal saline 1 mg/kg after 2 h after lavage, given the amount of intraperitoneal injection of saline solution. The expression of NF-κB in lung tissue was determined by immunohistochemistry.The levels of TNF-a, IL-10, TREM-1, and soluble TREM-1 (sTREM-1) in lung tissue and serum were measured by ELISA. Pathology changes of lung were observed under light microscope, and lung score of pathology was compared. Administration of anti-TREM-1 mAb after PQ poisoning modeling significantly increased the NF-κB expression in lung tissue at 48 h, resulting in a large number of pro-inflammatory cytokines releasing in the lung tissue and serum and lung pathology injury score increasing.Administration of LP17 after modeling significantly down-·regulated the expressions of NF-κB and proinflammatory cytokines, while led to a slight increase of anti-inflammatory cytokines and a decline of lung pathology injury score. TREM-1 may involve in inflammatory response by promoting the generation of inflammatory factors via NF-κB pathway, thus lead to lung pathological changes.

An association between single nucleotide polymorphisms within TLR and TREM-1 genes and infective endocarditis

Infective endocarditis (IE) is an inflammatory condition of the lining of the heart chambers and valves, which is generally caused by bacteria. Toll-like receptors (TLRs) and Triggering receptor expressed on myeloid cells (TREMs) are key effectors of the innate system that play a significant role in the recognition of infectious agents, particularly, bacteria. We hypothesised that inherited variation in TLR and TREM-1 genes may affect individual susceptibility to IE. The distribution of genotypes and alleles of the TLR1 (rs5743551, rs5743611), TLR2 (rs3804099, rs5743708), TLR4 (rs4986790, rs4986791), TLR6 (rs3775073, rs5743810), and TREM-1 (rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535, rs2234237) gene polymorphisms was investigated in 110 Caucasian (Russian) subjects with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors. Odds ratios with 95% confidence intervals were calculated. We found that C/C genotype of the rs3775073 polymorphism within TLR6 gene was associated with a decreased risk of IE (OR=0.51, 95% CI=0.26–0.97, P=0.032) according to the recessive model; however, we observed no association between the other investigated SNPs within TLR and TREM-1 genes and IE. Further in-depth investigations in this field are necessary to shed the light on the impact of inherited variation within innate immune response genes on the development of IE.

The expression of triggering receptor-1 on myeloid cells in severe acute pancreatitis-induced lung injury rats

Objective To investigate the expression of triggering receptor-1 on myeloid cells (TREM-1) and inflammatory cytokines in acute lung injury (ALI) incurred by severe acute pancreatitis (SAP).Methods Twenty-four male SD rats were randomly (random number) divided into sham operation (SO) group,SAP group and SAP + LP17 (synthesized TREM-1) group (n =8 in each group),and SAP model was established by retrograde injection of sodium taurocholate into the bile-pancreatic duct.Twelve hours after modeling,all rats of three groups were sacrificed,and the pancreas and lung of rats were harvested.The histopathological changes of pancreas and lung tissue stained with hematoxylin-eosin staining (HE staining) were observed under light microscope.The lung tissue was marked with macrophage-specific antibody CD68 to detect macrophage infiltration by using immunohistochemistry.The expressions of TREM-1 mRNA、interleukin-1β (IL-1β) mRNA and tumor necrosis factor-α (TNF-α) mRNA in lung tissue were detected by fluorescence quantitative polymerase chain reaction (QRT-PCR method).The data were expressed as ((-x) ± s) and SPSS 17.0 software was used to make one-way ANOVA,and P ＜ 0.05 was considered to indicate significant difference.Results Compared with SO group and SAP + LP17 group,the injuries of pancreas and lung tissue in SAP group were significantly more severe (P ＜ 0.05).In SAP group,macrophage infiltration in lung tissue was more evident than that in SO group.Accordantly,the expression of TREM-1 mRNA,IL-1β mRNA and TNF-α mRNA of lung tissue in SAP group were significantly higher than those in SO group and SAP + LP17 group (P ＜ 0.01 or P ＜ 0.05).Conclusions The expression of TREM-1 in the lung injury caused by SAP was significantly higher.It might be an important inflammatory mediator in the mechanism of lung injury caused by SAP.LP17 effectively lowered the expression of TREM-1 and decreased the release of inflammatory cytokines,lessening the lung injury. Key words: Severe acute pancreatitis; Acute lung injury; Triggering receptor-1 on myeloid cells; LP17 ; Interleukin-1β ; Tumor necrosis factor-α