Research Progress of TREM-1 in Immune-related Intestinal Diseases / 胃肠病学

Triggering receptor expressed on myeloid cells-1 (TREM-1), which plays a major role in the pathogenesis of infectious and non-infectious inflammation, is an important inflammation regulator. This article reviewed the structure and forms of TREM-1, mechanism on regulation of inflammation and relationship with immune-related intestinal diseases, thereby to investigate the role and potential value of TREM-1 on diagnosis, prognosis prediction and treatment target in immune-related intestinal diseases.

Effect and mechanism of monocytes/macrophages TREM-1 on acute lung injury in rats with severe heatstroke / 解放军医学杂志

Objective: To investigate the effect of the monocytes/macrophages on acute lung injury in rats with severe heatstroke, by modulating the expression of triggering receptor expressed on myeloid cells-1 (TREM-1). Methods: Forty rats were randomized evenly into the control group (Con group), heatstroke group (HS group), the low dose inhibitor group (LD group) and the high dose inhibitor group (HD group). Before heatstroke induction, the rats of LD and HD groups were administrated with a 50 mg/kg and 100 mg/kg bolus of LP-17, respectively. All rats were exposed to an environment with temperature of (40 ± 2) °C and humidity of 65% ± 5% for 60 minutes to induce heatstroke. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the concentration of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β in the peripheral blood and pulmonary tissue. The expression of TREM-1 on peripheral monocytes was identified by flow cytometry. Moreover, the histological phenotypes were evaluated after HE stain and the expression of inducible nitric oxide synthase (iNOS) was analyzed by immunohistochemistry in pulmonary tissues. Furthermore, Western blotting was used to detect the protein level of TREM-1 and monocyte chemoattractant protein-1 (MCP-1). Results: Compared to HS rat, in rats pretreated with LP-17, the levels of TNF-α, IL-6 and IL-1β in peripheral blood (P<0.01) and pulmonary tissue (P<0.01) were descended; the upregulation of TREM-1 on peripheral monocytes was alleviated in (P<0.01); the histological injury (P<0.01) were reduced; the protein levels of iNOS, TREM-1 and MCP-1 (P<0.01) were down-regulated. Conclusion: The down-regulation of the TREM-1 activity on the monocytes/macrophages in the peripheral blood and lung tissue by the bolus of LP-17 benefit to ameliorate the lung injury induced by heatstroke via inhibiting inflammation, oxidative stress and chemokine.

Effects of Dexmedetomidine Combined with Mild Hypothermia on the Levels of HMGB 1，TLR4 and Trem- 1 in Lung Tissues of Sepsis Model Rats / 中国药房

OBJECTIVE： To investigate the effects of dexmedetomidine combined with mild hypothermia on the levels of High mobility group box 1 protein （HMGB1）， Toll like receptor 4 （TLR4） and Triggering receptor expressed on myeloid cells 1 （Trem-1） in lung tissues of sepsis model rats. METHODS： Totally 100 SD rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， dexmedetomidine group （2 μg/kg）， mild hypothermia group （normal saline+anal temperature 32-35 ℃ caused by whole body spraying of cold water） and combination group （dexmedetomidine 2 μg/kg+anal temperature 32-35 ℃ caused by whole body spraying of cold water）， with 20 rats in each group. Except that sham operation group received sham operation， sepsis model was induced in other groups. After ligation and incision， the corresponding drugs were pumped into the jugular vein and the corresponding body temperature was maintained. Plasma samples were collected 6 h after operation. Interleukin 1 （IL-1）， IL-6， tumor necrosis factor α （TNF-α） were determined by ELISA. The lung wet mass/dry mass ratio （W/D） was calculated by weighing the mass. Lung tissue sections were observed by HE staining， and lung injury scores were scored. The activity of MPO in lung tissue was determined by immunoturbidimetry. The expression of HMGB1，TLR4 and Trem-1 protein was determined by Western blot. RESULTS： Compared with sham operation group， the contents of IL-1， IL-6 and TNF-α， W/D， lung injury score， MPO activity， the protein expression of HMGB1， TLR4 and Trem-1 were increased significantly， with statistical significance （P＜0.05）； lung tissue section showed that alveolar wall was obviously thickened； a large number of inflammatory cells infiltrated； blood vessels were obviously dilated and congested. Compared with model group， above indexes of rats in dexmedetomidine group， mild hypothermia group and combination group were decreased significantly， with statistical significance （P＜0.05）； the degree of pathological changes in lung tissue was significantly reduced. Compared with dexmedetomidine group and mild hypothermia group， above indexes of combination group were decreased more significantly， with statistical significance （P＜0.05）. Alveolar walls were thickened， inflammatory cell infiltration was relieved significantly and no vascular diatation and congestion was found. CONCLUSIONS： Dexmedetomidine combined with mild hypothermia can significantly improve lung injury in sepsis model rats， and down-regulate the protein expression of HMGB1， TLR4 and Trem-1. Therapeutic efficacy of combination therapy is better than single therapy.

Effect of Dahuang Mudan Tang in Triggering Receptor Expressed on Myeloid Cells-1 in Intestinal Tract in Rats with Septic Acute Intestinal Dysfunction / 中国实验方剂学杂志

Objective:To investigate whether the therapeutic effect of Dahuang Mudan Tang on septic acute intestinal dysfunction in sepsis ratsis related to the regulation of expression of triggering receptor expressed on myeloid cells-1(TREM-1). Method:Totally 100 male SD rats were injected intraperitoneally with lipopolysaccharide (LPS) at a dose of 4.5 mg·kg-1 to build sepsis model. The sepsis model rats were randomly divided into five groups:model group, glutamine group (3.75 g·kg-1),low,medium, high-dose Dahuang Mudan Tang group(7.5,15,30 g·kg-1),and another 10 normal rats were selected as normal group. Seven days later,2 mL suspension (100 mg lactulose and 50 mg mannitol) was orally administrated by gavage, and 24 h urinewas collected. The ratio of lactulose to mannitol in urine (L/M) was detected by HPLC with pulsed electrochemical detection (HPLC-PED).Serum citrulline concentrationsin blood and ileum were determined by HPLC.Enzyme linked immunesorbent assay (ELISA) was used to detect the concentrations of triggering receptor expressed on myeloid cells-1(TREM-1),tumor necrosis factor-α(TNF-α),intestinal fatty acid binding protein(iFABP) and D-lactic acid.Real-time PCR was used to detect the mRNA expressions of TREM-1,Toll-like receptors2(TLR2),Toll-like receptors 4(TLR4),myeloid cell differentiation protein(MyD88),nuclear transcription factor-κB(NF-κB).Electron microscopy was used to observe the pathological changes of intestinal mucosa injury. Result:Compared with normal group, the serum concentrations of TREM-1,TNF-α,iFABP, D-lactate; the ratio of lactulose to mannitol in urine (L/M)and the expressions of TREM-1,TLR2,TLR4,MyD88,NF-κB mRNA in model group were increased obviously(PPPPPκB mRNA,and the serum concentrations of TREM-1 and TNF-α in all medication administration groups were decreased obviously(PD-lactate, L/M, the Chiu scorein glutamine group, medium-dose Dahuang Mudan Tang group and high-dose Dahuang Mudan Tang group were decreased obviously(PPPConclusion:Dahuang Mudan Tang can effectively treat SAID in rats, and its mechanism may be realized by regulating the expression of TREM-1 and relieving intestinal inflammation of intestinal tract.

Effect of silencing TREM1 on rats with neuropathic pain / 临床麻醉学杂志

Objective To investigate the role of triggering receptor expressed on myeloid cells 1 (TREM1)in rats with neuropathic pain and its possible mechanism.Methods Forty-eight male a-dult Sprague-Dawley rats,weighing 220-300 g,were successfully placed intrathecal catheters,and then randomly divided into 4 groups (n=1 2 ):sham operation group (group S),neuropathic pain group (group CCI),TREM1 shRNA group (group RNAi)and negative lentivirus group (group Vi-rus).The neuropathic pain was induced by chronic sciatic nerve compression injury (CCI).In group RNAi,30 μl pGLVU6/RFP/Puro-shRNA (1×109IU/ml)was injected intrathecally 1 week before modeling.Group Virus was injected with 30 μl negative lentivirus,whereas group CCI and group S with equal amount of normal saline.MWT and TWL were measured 1 day before (baseline)and 1,3, 7,14 day after modeling.When behavioral test finished,the expression levels of TREM1,TLR4, MyD88,IκBαand p-NF-κB p65 in spinal cord were determined by Western blot.Whereas the mRNA expression levels of IL-1β,TNF-αand IL-6 in spinal cord were measured by RT-PCR.Results Com-pared with group S,the expression levels of TREM1 in groups CCI and Virus significantly increased (P<0.05).While compared with group CCI,the TREM1 expression of group RNAi in spinal cord significantly decreased (P<0.05).Compared with group S,MWT and TWL of groups CCI,Virus and RNAi after modeling and the expression of IκBαsignificantly decreased (P<0.05),whereas the expression of TLR4,MyD88,p-NF-κB p65 increased significantly (P<0.05),as well as the expres-sion of IL-1β,TNFαand IL-6 mRNA (P<0.05).Compared with group CCI,the MWT and TWL of group RNAi after modeling and the expression of IκBαremarkably increased (P<0.05),whereas the expression of TLR4,MyD88 and p-NF-κB p65 in the spinal cord remarkably decreased (P<0.05), as well as the expression of IL-1β,TNF-αand IL-6 mRNA (P<0.05).Conclusion TREM1 knock-down can alleviate neuropathic pain,the underlying mechanism might be the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Effect of sTREM-1 on prognosis of patients with ventilator-associated pneumonia / 中华急诊医学杂志

Objective To explore the prognostic value of soluble triggering receptor expressed on myeloid cells-1(sTREM-1) in patients with ventilator-associated pneumonia (VAP).Methods A total of 103 VAP patients were enrolled from June 2013 to May 2015 in the ICU of Wuxi People's Hospital Affiliated to Nanjing Medical University.The demographics and clinical data were collected,while serum sTREM-1,procalcitonin (PCT),C-reactive protein(CRP),clinical pulmonary infection score(CPIS) and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) were measured.Patients were divided into the death group and the survival group according to 28 d survival.The differences in demographics and clinical data were compared between groups.The values of sTREM-1,PCT,CPIS and APACHE Ⅱ for predicting 28 d death were evaluated by receiver operating curves(ROC).The surviving curve was drawn by Kaplan-Meier method.The possible prognostic factors were analyzed by univadate and logistic multivariate analysis.Results There were 76 patients in the survival group and 27 patients in the death group,and there was no difference in demographics between two groups(P＞0.05).The serum sTREM-1,PCT,CPIS and APACHE Ⅱ were higher in the death group[(89.50±18.45) pg/mL,(823.86±182.74) pg/ mL,(7.20±1.74) and (19.58±3.43)] than those in the survival group[(54.09±12.71) pg/mL,(579.81±193.45) pg/mL,(4.79±1.93) and (17.23±3.12),all P＜0.05].The areas under the ROC of sTREM-1,PCT,CPIS and APACHE Ⅱ for predicting 28 d death were 0.84±0.04(95％CI:0.75-0.92,P＜0.01),0.65±0.05(95％CI:0.55-0.74,P=0.49),0.67±0.06(95％CI:0.55-0.79,P＜0.01),0.79±0.04(95％CI:0.70-0.87,P=0.03),respectively.Patients were assigned into two groups by the best cutoffpoint of sTREM-l=75.00 pg/mL,and Kaplan-Meier survival analysis showed that 28 d survival rate in the low sTREM-1 group was significantly higher than that in the high sTREM-1 group (82.5％ vs.63.4％,x2=3.96,P＜0.05).Multivariate logistic regression analysis showed that both sTREM-1 (OR=1.08,95％CI:1.04-1.13,P＜0.01) andAPACHE Ⅱ (OR=1.39,95％CI:1.15-1.67,P＜0.01) were risk factors associated with 28 d death.Conclusions Early serum sTREM-1 can be used as a reliable predictor for the outcome of patients with VAP.

Relationship between TREM-1 gene polymorphism and susceptibility to coronary atherosclerotic heart disease / 中华检验医学杂志

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; χ2＝39.213, P＜0.01; χ2＝24.184, P＜0.01; t＝5.476, P＜0.01; t＝-5.106, P＜0.01, respectively).The distribution of rs2234237, rs9471535 genotypes and alleles was statistically significant in the two groups (rs2234237: χ2＝6.893, P＜0.05; χ2＝7.159,P＜0.05, respectively; rs9471535: χ2＝8.284, P＜0.05; χ2＝8.314, P＜0.05, respectively).The genotype frequency of rs2234237(AT+TT)in CHD group was significantly lower than in the control group (38.3% vs 53.3%,χ2＝4.680, P＝0.031), and the genotype frequency of rs9471535 ( AG +GG) in CHD group was significantly lower than in the control group (37.5% vs 53.3%, χ2＝5.225, P＝0.022) .In addition, the T allele frequency of rs2234237 in CHD group was significantly lower than in the control group (21.7%vs 33.3%, χ2＝7.159, P＝0.007) , and the G allele frequency of rs9471535 in CHD group was significantly lower than in the control group(20.8%vs 33.3%, χ2＝8.314, P＝0.004).The CHD risk of people carrying rs2234237 TT was 0.173 times of AA (95% CI: 0.048 -0.629, P＝0.008), and the CHD risk of people carrying rs9471535 GG was 0.108 times of AA(95% CI: 0.026-0.450, P＝0.002).However, carriers with T allele of rs2234237(AT+TT) or with G allele of rs9471535(AG+GG)were not significantly associated with the CHD risk(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.

Expressions of TREM-1 and COX-2 in rectal carcinomaand their relationship with prognosis / 西安交通大学学报(医学版)

Objective To detect the differences of triggering receptor expressed on myeloid cells-1 (TREM-1) and cyclo-oxygenase-2 (COX-2) expressions in rectal cancer tissues and carcinoma adjacent tissues so as to explore the relationship between the two factors and clinical pathological characteristics and their effects on the patients` survival.Methods The expressions of TREM-1 and COX-2 were analyzed in 68 cases of rectal cancer tissues and 58 cases of carcinoma adjacent tissues with the method of immunohistochemical staining.We made a regular follow-up of the patients, analyzed the relationship between the two factors and prognosis of rectal cancer.Results The positive expression rates of TREM-1 and COX-2 in rectal cancer tissues were higher than those in carcinoma adjacent tissues (P<0.05).The expression of TREM-1 was related to lymph node metastasis, while COX-2 was related to pathological stage and lymph node metastasis (P<0.05).However, the two factors were not related to age, sex, histological differentiation or tumor size.The expressions of the two factors were positively correlated (r=0.550, P<0.001).The overall survival (OS) of TREM-1 and COX-2 positive expression groups was shorter than that of the negative groups (P<0.05).Cox multiple regression analysis showed that the expression of TREM-1, pathological stage, lymph node metastasis and tumor size affected the prognosis.Conclusion The expressions of COX-2 and TREM-1 in rectal cancer increase, suggesting that the two factors may promote the development and lymph node metastasis of rectal cancer, and the expressions of the two factors are related to the patients` poor prognosis.

Soluble triggering receptor expressed on myeloid cells-1 as a diagnostic marker of ventilator-associated pneumonia in patients with acute ischemic stroke / 中国医师进修杂志

Objective To investigate the potential role of soluble triggering receptor expressed on ayeloid cells-1(sTREM-1) expression in serum,endotracheal aspiration (ETA),bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) as early biomarkers for the diagnosis of ventilator-associated pneumonia (VAP) in patients with acute ischemic stroke.Methods One hundred and thirty-two patients with clinically suspected VAP were prospectively included in this multicenter study.The levels of sTREM-1 in serum,ETA,BALF and EBC were analyzed for diagnostic evaluation at the time of VAP clinically suspected.The bacterial count over 104/CFU as a gold standard for VAP,and the receiver operating characteristic curves were used to identify the ideal cutoff values.Results VAP was confirmed in 76 patients (57.58％).In VAP patients (VAP group) and non-VAP patients (non-VAP group),the level of sTREM-1 in BALF was 32.35 (30.08-41.72) and 18.92(11.89-31.72) ng/L,and the level of sTREM-1 in EBC was 1.57 (1.02-2.61) and 0.41(0.19-1.61)ng/L respectively.The level of sTREM-1 in BALF and in EBC in VAP group was significantly higher than that in non-VAP group (P ＜0.05).The optimum cutoff value for sTREM-1 in BALF according to the maximum Youden index was 23.61 ng/L.This cutoff value had 85.5％ sensitivity and 73.1％ specificity,with 0.813 area under the curve.sTREM-1 in BALF had excellent correlation with that in EBC (R2 =0.78,P ＜ 0.05).Conclusions The results of this prospective study suggest that sTREM-1 levels in BALF and EBC have better roles in facilitating the diagnosis of VAP and thus may be practically recommended to guide the administration of antibiotics when VAP is suspected.

Relationship between intrapulmonaryTREM-1 and endoplasmic reticulum stress in mice with acute lung injury / 实用医学杂志

Objective To observe the correlation of intrapulmonary TREM-1 with endoplasmic reticulum stress in mice with acute lung injury (ALI).Methods Balb/c mice were tracheally injected with lipopolysaccharide(LPS,5 mg/kg) to induce ALI.Real-time PCR and Western blot were used to detect the expressions of TREM-1,CHOP and GRP78.The correlation of TREM-1 with endoplasmic reticulum-related proteins was analyzed.LPS (100 ng/mL) was used to induce inflammation in mouse primary peritoneal macrophages,and expressions of TREM -1,CHOP and GRP78 mRNA were detected by real-time PCR.The effect of TREM-1 activation on the expressions of CHOP and GRP78 was observed in macrophages.Results The expressions of TREM-1,CHOP and GRP78 mRNA were increased in ALI mice.TREM-1 mRNA expression was positively correlated with CHOP and GRP78 mRNA expression.In vitro,LPS up-regulated the expressions of TREM-1,CHOP and GRP78,and TREM-1 was positively correlated with CHOP and GRP78.Activation of TREM-1 increased CHOP and GRP78 mRNA expressions.Conclusions TREM-1 is positively related to the endoplasmic reticulum stress.The activation of TREM-1 enhances endoplasmic reticulum in mouse macrophages.

Effects of dexmedetomidine on mRNA expression of triggering receptor expressed on myeloid cells 1 in peripheral blood mononuclear cells of rats with acute obstructive suppurative cholangitis / 中国中西医结合急救杂志

Objective To investigate the effects of dexmedetomidine (DEX) on the mRNA expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in peripheral blood mononuclear cells of rats with acute obstructive suppurative cholangitis (AOSC).Methods Sixty healthy male Wistar rat models of AOSC induced by complete common bile duct ligation and injection of E.coli into the bile duct through an intubation tube were replicated successfully.After modeling,the peripheral blood was collected and mononuclear cells were isolated and cultured.According to random number table method,the mononeuclear cells were divided into model group (no drug added in culture of mononuclear cells) and low,medium and high dose DEX groups (final concentrations 0.4,0.8,1.2 μg/L DEX were in low,medium and high DEX mononuclear cell cultures,respectively).After the mononuclear cells were cultured for 24 hours,the levels of tumor necrosis factor-α (TNF-α),interleukins (IL-1 and IL-6) in the supernatant of the cultured mononuclear cells were detected by enzyme linked immunosorbent assay (ELISA).The level of C-reactive protein (CRP) was detected by immunity transmission turbidimetry.The expression of TREM-1 mRNA in the mononuclear cells was detected by reverse trantscription-polymerase chain reaction (RT-PCR).Results Compared with the model group,the levels of TNF-α,IL-1,IL-6,CRP were decreased,the TREM-1 mRNA expressions were down-regulated in the different DEX dose groups,and the degrees of descent in medium and high dose groups were more significant than those in low dose group [TNF-oα (ng/L):95.5±8.6,88.9±5.3 vs.131.1 ± 14.2;IL-1 (ng/L):53.5±8.3,48.3 ± 6.7 vs.73.7 ± 12.8;IL-6 (ng/L):266.9±26.2,252.1 ± 17.7 vs.349.9±40.4;CRP (ng/L):4.3 ± 1.1,3.9 ±0.7 vs.5.6 ± 1.7;TREM-1 mRNA (A value):0.43 ± 0.18,0.39 ± 0.16 vs.0.65 ±0.25,all P ＜ 0.05].Conclusion DEX can down-regulate the expression of TREM-1 mRNA and inhibit the formation and secretion of inflammatory factors TNF-α,IL-1,IL-6 and CRP in peripheral blood mononuclear cells of rats with ASOC.

Research progress on the relationship between triggering receptor expressed on myeloid cells 1 and 2 and malignant tumors / 华西口腔医学杂志

Increasing scientific evidence supports the positive relationship between inflammation and cancer development. The immune response initiated by pattern recognition receptors is critical to triggering of tumor-associated inflammation. Triggering receptor expressed on myeloid cells (TREM) is an immunoglobulin of the super transmembrane glycoprotein family, which is mainly expressed on select groups of myeloid cells. The most important members of TREM comprise TREM-1 and TREM-2. Activation of TREM-1 and TREM-2 signaling is initiated upon binding of their ligands. Subsequently, cross-linking reactions of downstream effectors occur, resulting in inflammation regulation. Recently, the connection between TREM and malignant tumors has been widely noticed and studied. This review summarizes studies of association between TREM-1, TREM-2, and malignant tumors in the medical field to provide new ideas for study on the correlation between periodontitis and oral cavity cancer.

The Detection and Clinical Value of Soluble Triggering Receptor Expressed on Myeloid Cells-1in Patients with Stable Chronic Obstructive Pulmonary Disease / 实用医学杂志

Objective To determine the value of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in patients with stable chronic obstructive pulmonary disease (sCOPD). Methods From 2015 January to 2015 August, 101 patients with stable chronic obstructive pulmonary disease and 81 healthy controls were en-rolled. All subjects underwent pulmonary function test to record FEV1%pred and FEV1%FVC and their serum sTREM-1 levels were determined. Arterial blood gas analyses and COPD assessment tests were also conducted in stable COPD patients. Results Serum sTREM-1 levels were significantly higher in stable COPD patients than healthy controls (113.2 ± 31.5 pg/mL and 83.8 ± 17.9 pg/mL respectively, P=0.000). sTREM-1 levels were posi-tively correlated with CAT score (r=0.507, P=0.000), whereas negatively correlated with FEV1%pred and PaO2 (r = 0.507, P = 0.000; r = 0.439, P = 0.000). Conclusion sTREM-1 is a promising biomarker to evaluate sCOPD in the future.

Expression of Trem-1 and its significance in psoriasis vulgaris / 西安交通大学学报(医学版)

Objective To study the expression of triggering receptor expressed on myeloid cells-1 (Trem-1)in psoriatic vulgaris and normal skin tissues and blood,and to explore the potential pathogenesis of psoriasis.Methods Immunohistochemistry and Real-time PCR were used to detect the expression of Trem-1 in the blood and tissues of normal skin and psoriasis.Results The positive expression rate of Trem-1 in psoriatic lesion was significantly higher than normal tissue.Trem-1 was expressed in the whole epidermis,with a significant difference (P<0.05). The mRNA expression of Trem-1 was significantly higher in psoriatic skin tissues and blood than in normal skin tissues and blood (P<0.05).Moreover,the mRNA expression of Trem-1 was positively correlated with PASI (P<0.05).Conclusion Abnormal expression of Trem-1 might be related to the pathogenesis of psoriasis.Trem-1 will cure psoriasis vulgaris as the potential therapeutic target.

Study of diagnostic value of neutrophil CD64 and sTREM-1 in elderly patients with community-acquired pneumonia / 中国免疫学杂志

Objective:To explore the neutrophil CD64 and sTREM-1 in elderly patients with community-acquired pneumonia ( CAP) in the diagnosis of clinical value. Methods: 76 elderly CAP hospitalized patients were divided into severe pneumonia group (n=23) (live in 15 cases,8 deaths)and ordinary pneumonia group(n=53) according to severity;45 patients in the control group compared with healthy older persons. Peripheral blood neutrophil CD64 was measured by automatic flow cytometry,sTREM-1 levels was measured by double-antibody sandwich enzyme-linked immunosorbent assay. The receiver operating characteristic curve ( ROC curve) was used to check diagnostic value of the detection. Results: Median concentrations of CD64 and sTREM-1 in the severe pneumonia group,general pneumonia group and control group were 37. 49,18. 82 and 10. 63 MFI,and 75. 39,65. 31 and 43. 96 pg/ml, respective-ly. Although there was significant differences among the three groups ( P<0. 05 ); CD64 and sTREM-1 in Severe pneumonia survival group reduced to a normal level as his condition improved gradually,death group continued to rise as the disease,and peaked at the time of death;the area under the ROC curve of CD64,sTREM-1were respectively 0. 876,0. 843,which was 0. 917 by combination of CD64 and sTREM-1. Conclusion: Both CD64 and sTREM-1 are good markers in the diagnosis value of CAP, the dynamic changes of two may reflect the condition and prognosis of CAP.

Abnormality and significance of monocyte subsets in peripheral blood of patients with rheumatoid arthritis / 中国免疫学杂志

Objective:To explore the role of peripheral blood monocyte subsets in the pathogenesis of rheumatoid arthritis (RA),we therefore decided to compare the percentage of monocyte subpopulations in peripheral blood,as well as cytokines secretion function,to that of healthy controls. Methods:22 patients with RA and 22 cases of healthy controls ( HC) were drew 3 ml fresh venous blood into a tube containing heparin. The percentage of monocyte subsets,expression of Toll-like receptor(TLR)2,HLA-DR,triggering receptor expressed on myeloid cells-1(TREM-1) on intermediate monocyte and mean fluorescence intensity(MFI) of intracellular tumor necrosis factor-α ( TNF-α) were evaluated with the methods of flow cytometry ( FCM ) . The correlation between percentage of monocyte subsets and serum cytokines was explored. Statistical significance between parametric data was determined by the students't-test. Results:Compared to HC controls, the percentages of intermediate monocytes were significant higher in RA patients [ ( 11. 7 ± 1. 6)% vs (4. 6±1. 2)%,P0. 05),while MFI of intracellular TNF-αin intermediate monocytes of RA patients were significant higher than that of HC controls (46. 3±6. 4 vs 36. 7±8. 3,P<0. 05). In addition,RA patients showed a positive correlation between the percentage of CD14highCD16+ monocytes and DAS28 scores(r=0. 538,P=0. 009),as well as the serum levels of TNF-α,IL-17 ( r=0. 471,P=0. 027;r=0. 593,P=0. 003). Conclusion:Monocyte subpopulations from RA patients are abnormally skewed toward to in-termediate monocytes which has high expression of TLR2 , TREM-1 and the function of TNF-α secretion. Therefore, intermediate monocytes may play a role in the pathophysiology of RA. By modulating polarization or blocking monocyte cell surface receptors could be a new treatment of RA.

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population / 世界急诊医学杂志（英文）

@#BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock. METHODS: We genotyped two TREM-1 single nucleotide polymorphisms (SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis. RESULTS: TREM-1 rs2234246 A allele in the promoter region was significantly associated with the susceptibility of septic shock in recessive model (AA, OR=3.10, 95％Cl 1.15 to 8.32, P=0.02), and in codominant model (AG, OR=0.72, 95％Cl 0.43–1.19, P=0.02; AA, OR=2.71, 95％Cl 1.00–7.42;P=0.03). However, in three inherited models (dominant model, recessive model, and codominant model), none of the assayed loci was significantly associated with the prognosis of septic shock. The non-survivor group demonstrated higher plasma IL-6 levels (99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/mL, AG 85.4±43 pg/mL, and GG 65.3±30.7 pg/mL (P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were significantly higher than those in patients with GG genotypes (P<0.01). CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.

Usefulness of Various Biomarkers for the Differentiation of Bacterial from Viral Meningitis.

Background and Aim: Meningitis is an emergency condition, particularly bacterial meningitis for young and elderly patients. Differentiation between septic and aseptic meningitis may be difficult, the search for biochemical markers and laboratory tests to help in this task is crucial in order to optimize the treatment and avoid unnecessary use of antibiotics especially in aseptic meningitis. The aim of this study was to evaluate the diagnostic and prognostic utility of sTREM-1, CRP, IL-8 in septic meningitis and their usefulness in early differentiation between septic and aseptic meningitis in Egyptian patients. Patients and Methods: This work included 70 patients (25 had septic meningitis group I, 30 had aseptic meningitis group II and 15 control individual group III). sTREM-1, IL-8 and CRP measurements were done on admission and after 48-72 h of treatment, in addition to Gram stain, culture of blood and CSF, latex agglutination test of CSF. Results: Bacterial (septic) meningitis was found in 25 (35.7%) of the studied groups. Patients with septic meningitis had a significant increase in serum sTREM-1 and IL-8 and CRP at the time of admission (32.9919.79, 2.461.8 and 12690.5 respectively) while patients with aseptic meningitis had (6.85.67, 0.660.118 and 3525.38 respectively), the control group had (6.64.6, 0.0550.07 and 154 respectively) (P<0.05). sTREM-1 showed significant higher sensitivity (93.7%) and specificity (94.3%) in the early prediction of sepsis with an area under the receiver operator characteristic (ROC) curve (95% CI) of 88.2 (84-93) at a cut off value of 12.4 ng/ml. Moreover, sTREM-1 level was significantly low (P<0.001) at admission in 6 patients out of 25 patients who had septic meningitis who showed poor outcome. Conclusion: sTREM-1 and IL-8 are valuable in early distinguishing of septic from aseptic meningitis but with higher diagnostic discriminatory power for sTREM-1 in determining septic meningitis prognosis and this marker would facilitate the clinical decision of interrupting antimicrobial therapy and avoiding unnecessary hospitalization.

Effect of TREM-1 expression on the apoptosis of intestinal macrophages of rats / 中华急诊医学杂志

Objective To investigate the effect of triggering receptor expression in myeloid cells-1 (TREM-1) on intestinal macrophage apoptosis in rat.Methods In vitro,the achieved rat intestinal macrophages were divided into 3 groups:control group,LPS (Lipopolysaccharides) group and LPS + LP17 group (n =6 holes of culture plate in each).The concentrations of LPS and LP17 were 1 mg/L and 0.1 mg/L,respectively.The intestinal macrophage apoptosis was measured by using TUNEL kit and flow cytometry after culture for 6 h.All data were statistically analyzed using SPSS 18.0 software.Results The shape and growth of rat intestinal macrophages were quite favorable after culture.The membrane marker of intestinal macrophages,CD14 was clearly observed under immunofluorescence.After macrophage was treated with specific procedure,the cell apoptosis found in LPS group (44.33 ± 7.74)％ was significantly higher than that in control group (19.17 ± 6.01) ％ (P=0.000) measured by TUNEL;the cell apoptosis in LPS +LP17 group (28.33 ± 6.53)％ apparently reduced compared with LPS group (44.33 ±7.74) ％ (P =0.004);there was no significant difference in cell apoptosis between control group (19.17 ± 6.01) ％ and LPS + LP17 group (28.33 ± 6.53) ％ (P =0.050).By flow cytometry,the apoptotic cells in LPS group (16.47 ± 1.66) ％ was significantly increased compared with control group (7.70 ± 1.52) ％ (P =0.000);apoptotic cells in LPS + LP17 group (11.47 ± 3.12) ％ was significantly reduced in comparison with LPS group (16.47 ± 1.66) ％ (P =0.018).There was no significant difference in apoptotic cells between control group (7.70±1.52)％ and LPS + LP17 group (11.47±3.12) ％ (P =0.061).Conclusion LP17 can inhibit TREM-1 expression in intestinal macrophages and reduce intestinal macrophage apoptosis.

Change and significance of the soluble triggering receptor expressed of myeloid cells-1 and soluble urokinase plasminogen activator receptor expression in children with sepsis / 中华实用儿科临床杂志

Objective To investigate the change and clinical significance of soluble triggering receptor expression of myeloid cells-1 (sTREM-1) and soluble urokinase plasminogen activator receptor (suPAR) expression in children with sepsis.Methods There were 80 systemic inflammatory response syndrome (SIRS)patients who were included in the study,60 cases in the sepsis group,20 cases in the non-infectious SIRS group and 30 cases in the healthy control group.By using the enzyme-linked immunosorbent assay (ELISA)to dynamically monitor the levels of serum sTREM-1,suPAR in children with sepsis,the differences of sTREM-1,suPAR levels between children with sepsis and non-sepsis were observed,the correlation with the pediatric critical illness score(PCIS) was analyzed,and the sensitivity and specificity of sTREM-1,suPAR,C-reactive protein (CRP)and procalcitonin (PCT)and other biochemical markers were compared,and the value of sTREM-1,suPAR,CRP,PCT in the early determination and prognosis of sepsis were investigated.Results Serum sTREM-1,suPAR,PCT levels in sepsis group were significantly higher than non-infectious SIRS group and the healthy control group,and the difference was statistically significant (P ＜ 0.05),but the differences of serum CRP levels in non-infectious SIRS group and sepsis group were not statistically significant(P ＞ 0.05).In sepsis subgroup,serum sTREM-1,suPAR,PCT levels between the three groups were of statistically significant difference (P ＜ 0.05).Through dynamic monitoring of sepsis group,serum sTREM-1,suPAR,CRP,PCT levels had a gradual downward trend in 1,4,7 day,at each time point difference was statistically significant (P ＜ 0.05).Serum sTREM-1,suPAR levels in sepsis group had significant negative correlation with PCIS (r =-0.322,-0.333,P ＜ 0.05).The sensitivity and specificity of sTREM-1,suPAR,CRP,PCT on diagnosing sepsis were in a descending order,and sTREM-1 combined with suPAR has the highest sensitivity and specificity.Conclusions sTREM-1 and suPAR all can serve as indicators of infection and inflammation,as their expression level can reflect the severity of sepsis.sTREM-1 combined with suPAR diagnostic sensitivity and specificity of sepsis was significantly better than a single indicator of sTREM-1,suPAR,CRP,PCT.Combining multiple indicators can improve the accuracy of diagnosis.