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 infl ammation and serves as a critical mediator of infl am...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 infl ammation and serves as a critical mediator of infl ammatory 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 signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 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 signif icantly associated with the prognosis of septic shock. The nonsurvivor 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/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly 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.展开更多
Background: Major abdominal surgery, including colorectal cancer (CRC) surgery, leads to systemic inflammatory response syndrome that can be detected and monitored with inflammatory markers testing. The aims of the...Background: Major abdominal surgery, including colorectal cancer (CRC) surgery, leads to systemic inflammatory response syndrome that can be detected and monitored with inflammatory markers testing. The aims of the study were to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-l (sTREM-1 ), interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) in following the inflammatory response in CRC surgery and postoperative period, as well as to determine if duration of the surgery and the time that the colon has been opened during the surgery (open colon time [OCT]) refect a larger surgical stress through inflammatory markers rise. Methods: The study included 20 patients who underwent CRC surgery and 19 healthy volunteers from June 2011 to September 2012. We determined inflammatory markers 1 day before surgery (T0), 24 h (T1), 48 h (T2), and 7 days after the surgery (T3). All statistical analyses were calculated using MedCalc Statistical Software version 14.8.1 (MedCalc Software bvba, Ostend, Belgium). Results: Concentrations ofCRP, PCT, and I L-6 in all measurement times were statistically different and sTREM- 1 did not yield statistical significance. A weak positive correlation was/bund between l L-6 in T 1 and T2 with the duration of the surgery (T 1 : r= 0.4060, P 〈 0.0001 ; T2:r =0.3430, P〈0.0001)andOCT(T1:r= 0.3640, P〈0.0001,T2:r=0.3430, P〈0.0001).AweakpositivecorrelationbetweenCRP in T2 and OCT (r = 0.4210, P 〈 0.0001 ) was also found. The interconnectivity of tested parameters showed a weak positive correlation between CRP and IL-6 in T1 (r= 0.3680; P 〈 0.0001 ), moderate positive correlation in T2 (r = 0.6770; P 〈 0.0001), and a strong positive correlation in T3 (r = 0.8651; P 〈 0.0001). Conclusions: CRP, IL-6, and PCT were shown to be reliable for postoperative monitoring. Simultaneous determination of CRP and IL-6 might not be useful as they follow similar kinetics, sTREM- 1 might not be useful in CRC postoperative monitoring.展开更多
Triggering receptor expressed on myeloid cells 2(TREM2)is a membrane receptor on myeloid cells and plays an important role in the body’s immune defense.Recently,TREM2 has received extensive attention from researchers...Triggering receptor expressed on myeloid cells 2(TREM2)is a membrane receptor on myeloid cells and plays an important role in the body’s immune defense.Recently,TREM2 has received extensive attention from researchers,and its activity has been found in Alzheimer’s disease,neuroinflammation,and traumatic brain injury.The appearance of TREM2 is usually accompanied by changes in apolipoprotein E(ApoE),and there has been a lot of research into their structure,as well as the interaction mode and signal pathways involved in them.As two molecules with broad and important roles in the human body,understanding their correlation may provide therapeutic targets for certain diseases.In this article,we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development.We further discussed the positive or negative effects of the TREM2-ApoE pathway on nervous system immunity and inflammation.展开更多
BACKGROUND:Triggering receptor expressed on myeloid cells-1 (TREM-1) in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased...BACKGROUND:Triggering receptor expressed on myeloid cells-1 (TREM-1) in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis (SAP), suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS: Sixty-four male Wistar rats were randomly divided into a sham operation group (SO group, n=32) and a SAP group (n=32). A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase (DAO) and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group (P〈0.01, P〈0.05). The expression levels of TREM-1, IL-1β and TNF-a mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group (P〈0.01, P〈0.05). The expression level of TREM-lmRNA was positively correlated with IL-1βand TNF-α mRNA (r=0.956, P=0.044; r=0.986, P=0.015), but the correlation was not found between IL-1β mRNA and TNF-a mRNA (P=0.133). Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS: The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-I might play an important role in the development of intestinal barrier dysfunction in rats with SAP.展开更多
BACKGROUND: Myeloid cell (TREM-1) is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury (ALl) by intraperitoneal injection of lipo...BACKGROUND: Myeloid cell (TREM-1) is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury (ALl) by intraperitoneal injection of lipopolysaccharide (LPS) was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS: Thirty BALB/C mice were randomly divided into a normal control group (n=6) and an ALl group (n=24). The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS: The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA (P=0.14); the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score (r=0.795, P=0.001 :r=0.499, P=0.034), but not with the expression of TREM-1 mRNA (P=0.176).CONCLUSION: The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.展开更多
Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is...Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases, sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g., Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g., Aspergillus infection), and burn-related infections, sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.展开更多
BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accu...BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.展开更多
Background: Triggering receptor expressed on myeloid cell- 1 (TREM- 1) may play a vital role in mammalian target ofrapamycin (mTOR) modulation ofCD8+ T-cell differentiation through the transcription factors T-bo...Background: Triggering receptor expressed on myeloid cell- 1 (TREM- 1) may play a vital role in mammalian target ofrapamycin (mTOR) modulation ofCD8+ T-cell differentiation through the transcription factors T-box expressed in T-cells and eomesodermin during the immune response to invasive pulmonary aspergillosis (IPA). This study aimed to investigate whether the roTOR signaling pathway modulates the proliferation and differentiation of CD8+ T-cells during the immune response to I PA and the role TREM-1 plays in this process. Methods: Cyclophosphamide (CTX) was injected intraperitoneally, and Asl?e;gillus.[mnigams spore suspension was inoculated intranasally to establish the immunosuppressed IPA mouse model. After inoculation, rapamycin (2 mg-kg ·d -1) or interleukin (IL)-12 (5 μg/kg every other day) was given for 7 days. The number of CD8+ effector memory T-cells (Tern), expression of interferon (IFN)-y, roTOR, and ribosomal protein $6 kinase (S6K), and the levels of IL-6, IL- 10, galactomannan (GM), and soluble TREM- 1 (sTREM-I) were measured. Results: Viable A. fumigatus was cultured from the lung tissue of the inoculated mice. Histological examination indicated greater inflammation, hemorrhage, and lung tissue injury in both IPA and CTX + IPA mice groups. The expression of mTOR and S6K was significantly increased in the CTX + IPA + I L- 12 group compared with the control, I PA (P = 0.01 ; P - 0.001 ), and CTX + 1PA (P = 0.034; P = 0.032) groups, but significantly decreased in the CTX + IPA + RAPA group (P 〈 0.001 ). Compared with the CTX + IPA group, the proportion of Tern, expression of IFN-y, and the level ofsTREM-I were significantly higher after IL-12 treatment (P = 0.024, P = 0.032, and P = 0.017, respectively), and the opposite results were observed when the roTOR pathway was blocked by rapamycin (P 〈 0.001). Compared with the CTX + I PA and CTX + I PA + RAPA groups, IL-12 treatment increased IL-6 and downregulated IL- 10 as well as G M, which strengthened the immune response to the IPA infection. Conclusions: mTOR modulates CD8+ T-cell differentiation during the immune response to IPA. TREM-1 may play a vital role in signal transduction between mTOR and the downstream immune response.展开更多
AIM: 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.METHODS: A total of 65 Wist...AIM: 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.METHODS: 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 72 h 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-1through 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.RESULTS: 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 24 h and 48 h after fungal infection.Immunofluorescence technique showed that TREM-1mainly 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-1expression in FK(r =0.942, P =0.000).CONCLUSION: TREM-1 may contribute to amplify theinflammation in the cornea infected with A. fumigatus and play critical roles in the battle against A. fumigatus in the innate immune responses.展开更多
BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that...BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that a 19-gene-based risk classifier(TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging.AIM To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology.METHODS A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival(PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction(qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry(IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro.RESULTS In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen(P = 0.041).In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7(SLAMF7) and triggering receptor expressed on myeloid cells 1(TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR,and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD73 were significantly lower at day 5 of co-culture than at day 0.CONCLUSION The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.展开更多
Objective:To investigate the application of peripheral blood triggering receptor expressed on myeloid cells-1(TREM-1)for sequential treatment switching points in patients with chronic obstructive pulmonary disease(COP...Objective:To investigate the application of peripheral blood triggering receptor expressed on myeloid cells-1(TREM-1)for sequential treatment switching points in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:A total of 120 cases of COPD patients with respiratory failure from June 2017 to December 2018 were randomly divided into two groups:60 cases in the control group and 60 cases in the observation group.The control group received spontaneous breathing trials for 2 h to select the time for non-invasive positive pressure ventilation,while the observation group received peripheral blood TREM-1(≤90.0 pg/mL)to select the time for non-invasive positive pressure ventilation.The stress hormones,clinical pulmonary infection score and vital signs of two groups after 24 h of mechanical ventilation were detected.The treatment time and the adverse reactions of the two groups were recorded.Results:There was no significant difference in rennin,adrenaline,noradrenaline and angiotensin II between two groups(P>0.05).Compared with the control group,the clinical pulmonary infection score was decreased in the observation group(P<0.05).There was no significant difference in heart rate,respiratory rate,pH,partial pressure of carbon dioxide and partial pressure of oxygen between two groups(P>0.05).There was no significant difference in intensive care monitoring time between two groups(P>0.05).Compared with the control group,the observation group had no significant difference in invasive ventilation time and total mechanical ventilation.The time of hospitalization and hospitalization had significantly decreased(P<0.05).There was no significant difference in mortality,ventilator-associated pneumonia and re-intubation between two groups(P>0.05).Conclusion:TREM-1 can be used as a switching point during invasive-noninvasive sequential ventilation for COPD patients with respiratory failure,which can shorten the time of invasive ventilation,total mechanical ventilation and hospitalization.展开更多
OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying s...OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying signaling pathway that mediate TREM2 function.METHODS TREM2 adenovirus were stereologically injected into the right striatum.Two weeks later,MPTP was intraperitoneally injected to produce the acute MPTP mouse model of PD.Mice were sacrificed at different time points following MPTP for biochemical or histological study.RESULTS Overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo.Further study revealed that TREM2 may inhibit neuroinflammation by negatively regulating the TRAF6/TLR4-mediated activation of the MAPK and NF-κB signaling pathways.CONCLUSION TREM2 may have important neuroprotective effects against PD by critical y modulating neuroinflammatory responses.展开更多
Objective: To investigate the correlation of serum soluble triggering receptors expressed on myeloid cells 1 (sTREM-1) content with inflammatory factors and immune function in neonatal infectious pneumonia. Methods: A...Objective: To investigate the correlation of serum soluble triggering receptors expressed on myeloid cells 1 (sTREM-1) content with inflammatory factors and immune function in neonatal infectious pneumonia. Methods: A total of 62 neonates with infectious pneumonia who were treated in Xiaogan Hospital Affiliated to Wuhan University of Science and Technology between July 2016 and September 2017 were selected as pneumonia group, and 50 healthy neonates who were born in this hospital during the same period were selected as normal control group. The differences in serum levels of sTREM-1, inflammatory factors and immunoglobulins were compared between the two groups. Results: Serum sTREM-1 content of pneumonia group was higher than that of normal control group;serum cytokines IL-10, IL-17, PCT and CRP contents were higher than those of normal control group;serum immunoglobulins IgA, IgG and IgM contents were higher than those of normal control group;serum IL-10, IL-17, PCT, CRP, IgA, IgG and IgG contents of pneumonia group of neonates with high serum sTREM-1 content were higher than those of neonates with low serum sTREM-1 content. Conclusion: Serum sTREM-1 content is higher in neonates with infectious pneumonia, which is directly correlated with the inflammatory response and humoral immune function.展开更多
Objective: To study the correlation of serum HMGB1 and sTLT-1 contents with oxidative stress response and endothelial injury in patients with ischemic stroke. Methods: The patients who were diagnosed with ischemic str...Objective: To study the correlation of serum HMGB1 and sTLT-1 contents with oxidative stress response and endothelial injury in patients with ischemic stroke. Methods: The patients who were diagnosed with ischemic stroke in Zhouzhi County People's Hospital between February 2015 and March 2017 were selected as the stroke group of the study, and healthy subjects who received physical examination during the same period were selected as the control group of the study. Serum was collected to determine the contents of HMGB1, sTLT-1, oxidative stress reaction molecules and endothelial injury molecules. Results: Serum HMGB1, sTLT-1, vWF, vWF-cp, sTM, ET-1, D-D, 8-OHdG, LPO and NOS contents of stroke group were significantly higher than those of control group while T-SOD and GSH-Px contents were significantly lower than those of control group;serum T-SOD and GSH-Px contents of stroke patients with high HMBG-1 content were significantly lower than those of stroke patients with low HMBG-1 content while 8-OHdG, LPO and NOS contents were significantly higher than those of stroke patients with low HMBG-1 content;serum vWF, vWF-cp, sTM, ET-1 and D-D contents of stroke patients with high sTLT-1 content were significantly higher than those of stroke patients with low sTLT-1 content. Conclusion: The abnormally elevated HMGB1 and sTLT-1 in serum of patients with ischemic stroke can induce oxidative stress response and aggravate endothelial injury.展开更多
基金supported by Science&Technology Pillar Program of Guangdong Province(2009BAI86B03)
文摘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 infl ammation and serves as a critical mediator of infl ammatory 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 signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 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 signif icantly associated with the prognosis of septic shock. The nonsurvivor 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/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly 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.
文摘Background: Major abdominal surgery, including colorectal cancer (CRC) surgery, leads to systemic inflammatory response syndrome that can be detected and monitored with inflammatory markers testing. The aims of the study were to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-l (sTREM-1 ), interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) in following the inflammatory response in CRC surgery and postoperative period, as well as to determine if duration of the surgery and the time that the colon has been opened during the surgery (open colon time [OCT]) refect a larger surgical stress through inflammatory markers rise. Methods: The study included 20 patients who underwent CRC surgery and 19 healthy volunteers from June 2011 to September 2012. We determined inflammatory markers 1 day before surgery (T0), 24 h (T1), 48 h (T2), and 7 days after the surgery (T3). All statistical analyses were calculated using MedCalc Statistical Software version 14.8.1 (MedCalc Software bvba, Ostend, Belgium). Results: Concentrations ofCRP, PCT, and I L-6 in all measurement times were statistically different and sTREM- 1 did not yield statistical significance. A weak positive correlation was/bund between l L-6 in T 1 and T2 with the duration of the surgery (T 1 : r= 0.4060, P 〈 0.0001 ; T2:r =0.3430, P〈0.0001)andOCT(T1:r= 0.3640, P〈0.0001,T2:r=0.3430, P〈0.0001).AweakpositivecorrelationbetweenCRP in T2 and OCT (r = 0.4210, P 〈 0.0001 ) was also found. The interconnectivity of tested parameters showed a weak positive correlation between CRP and IL-6 in T1 (r= 0.3680; P 〈 0.0001 ), moderate positive correlation in T2 (r = 0.6770; P 〈 0.0001), and a strong positive correlation in T3 (r = 0.8651; P 〈 0.0001). Conclusions: CRP, IL-6, and PCT were shown to be reliable for postoperative monitoring. Simultaneous determination of CRP and IL-6 might not be useful as they follow similar kinetics, sTREM- 1 might not be useful in CRC postoperative monitoring.
基金Natural Science Foundation of Zhejiang Province in China(No.LY20H150009)
文摘Triggering receptor expressed on myeloid cells 2(TREM2)is a membrane receptor on myeloid cells and plays an important role in the body’s immune defense.Recently,TREM2 has received extensive attention from researchers,and its activity has been found in Alzheimer’s disease,neuroinflammation,and traumatic brain injury.The appearance of TREM2 is usually accompanied by changes in apolipoprotein E(ApoE),and there has been a lot of research into their structure,as well as the interaction mode and signal pathways involved in them.As two molecules with broad and important roles in the human body,understanding their correlation may provide therapeutic targets for certain diseases.In this article,we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development.We further discussed the positive or negative effects of the TREM2-ApoE pathway on nervous system immunity and inflammation.
基金The study was supported by a grant from the National Natural Science Foundation of China (81070287).
文摘BACKGROUND:Triggering receptor expressed on myeloid cells-1 (TREM-1) in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis (SAP), suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS: Sixty-four male Wistar rats were randomly divided into a sham operation group (SO group, n=32) and a SAP group (n=32). A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase (DAO) and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group (P〈0.01, P〈0.05). The expression levels of TREM-1, IL-1β and TNF-a mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group (P〈0.01, P〈0.05). The expression level of TREM-lmRNA was positively correlated with IL-1βand TNF-α mRNA (r=0.956, P=0.044; r=0.986, P=0.015), but the correlation was not found between IL-1β mRNA and TNF-a mRNA (P=0.133). Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS: The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-I might play an important role in the development of intestinal barrier dysfunction in rats with SAP.
文摘BACKGROUND: Myeloid cell (TREM-1) is an important mediator of the signal transduction pathway in inflammatory response. In this study, a mouse model of acute lung injury (ALl) by intraperitoneal injection of lipopolysaccharide (LPS) was established to observe the expression pattern of TREM-1 in lung tissue and the role of TREM-1 in pulmonary inflammatory response to ALl.METHODS: Thirty BALB/C mice were randomly divided into a normal control group (n=6) and an ALl group (n=24). The model of ALl was made by intraperitonal injection of LPS in dose of 10 mg/ kg. Specimens from peripheral blood and lung tissue were collected 6, 12, 24 and 48 hours after LPS injection. RT-PCR was used to detect TREM-1 mRNA, and ELISA was employed for detection of TREM-1 protein and TNF-a protein, and HE staining was performed for the pathological Smith lung scoring under a light microscope.RESULTS: The expressions of TREM-1 mRNAin lung tissue and blood of the ALl group 6, 12, 24, and 48 hours after injection of LPS were higher than those in the control group. The levels of TREM- 1 protein and the levels of TNF-a protein in lung tissue of the ALl group 6, 12, 24, and 48 hours after LPS injection were higher than those of the control group; the level of TREM-1 protein peaked 12 hours after LPS injection, but it was not significantly correlated with the expression of TREM-1 mRNA (P=0.14); the TNF-a concentration was positively correlated with TREM-1 levels in lung tissue and with Smith pathological score (r=0.795, P=0.001 :r=0.499, P=0.034), but not with the expression of TREM-1 mRNA (P=0.176).CONCLUSION: The expression of TREM-1 mRNA in lung tissue of mice with ALl is elevated, and the expression of TREM-1 mRNA is related to the level of TNF-a and the severity of inflammatory response to ALl. The expressions of the TREM-1 gene are not consistent with the levels of TREM-1 protein, suggesting a new functional protein involved in immune regulation.
文摘Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases, sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g., Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g., Aspergillus infection), and burn-related infections, sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.
基金National Natural Science Foundation of China,No.81970550,No.82070613 and No.82370638Natural Science Foundation of Hunan Province,China,No.2021JJ31067 and No.2021JJ41048+1 种基金Hunan innovative province construction project,No.2023JJ10095Innovative Talented Project of Hunan province,China,No.2022RC1212.
文摘BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.
文摘Background: Triggering receptor expressed on myeloid cell- 1 (TREM- 1) may play a vital role in mammalian target ofrapamycin (mTOR) modulation ofCD8+ T-cell differentiation through the transcription factors T-box expressed in T-cells and eomesodermin during the immune response to invasive pulmonary aspergillosis (IPA). This study aimed to investigate whether the roTOR signaling pathway modulates the proliferation and differentiation of CD8+ T-cells during the immune response to I PA and the role TREM-1 plays in this process. Methods: Cyclophosphamide (CTX) was injected intraperitoneally, and Asl?e;gillus.[mnigams spore suspension was inoculated intranasally to establish the immunosuppressed IPA mouse model. After inoculation, rapamycin (2 mg-kg ·d -1) or interleukin (IL)-12 (5 μg/kg every other day) was given for 7 days. The number of CD8+ effector memory T-cells (Tern), expression of interferon (IFN)-y, roTOR, and ribosomal protein $6 kinase (S6K), and the levels of IL-6, IL- 10, galactomannan (GM), and soluble TREM- 1 (sTREM-I) were measured. Results: Viable A. fumigatus was cultured from the lung tissue of the inoculated mice. Histological examination indicated greater inflammation, hemorrhage, and lung tissue injury in both IPA and CTX + IPA mice groups. The expression of mTOR and S6K was significantly increased in the CTX + IPA + I L- 12 group compared with the control, I PA (P = 0.01 ; P - 0.001 ), and CTX + 1PA (P = 0.034; P = 0.032) groups, but significantly decreased in the CTX + IPA + RAPA group (P 〈 0.001 ). Compared with the CTX + IPA group, the proportion of Tern, expression of IFN-y, and the level ofsTREM-I were significantly higher after IL-12 treatment (P = 0.024, P = 0.032, and P = 0.017, respectively), and the opposite results were observed when the roTOR pathway was blocked by rapamycin (P 〈 0.001). Compared with the CTX + I PA and CTX + I PA + RAPA groups, IL-12 treatment increased IL-6 and downregulated IL- 10 as well as G M, which strengthened the immune response to the IPA infection. Conclusions: mTOR modulates CD8+ T-cell differentiation during the immune response to IPA. TREM-1 may play a vital role in signal transduction between mTOR and the downstream immune response.
基金Supported by National Natural Science Foundation of China(No.81170825)
文摘AIM: 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.METHODS: 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 72 h 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-1through 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.RESULTS: 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 24 h and 48 h after fungal infection.Immunofluorescence technique showed that TREM-1mainly 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-1expression in FK(r =0.942, P =0.000).CONCLUSION: TREM-1 may contribute to amplify theinflammation in the cornea infected with A. fumigatus and play critical roles in the battle against A. fumigatus in the innate immune responses.
基金Korea Research Foundation,No.2016R1E1A1A02919844 to Kim JC and No.2017R1A2B1009062 to Roh SAMinistry of Science,ICT,and Future Planning,Republic of Koreathe Asan Institute for Life Sciences,No.2016-710 to Lee JL
文摘BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that a 19-gene-based risk classifier(TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging.AIM To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology.METHODS A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival(PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction(qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry(IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro.RESULTS In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen(P = 0.041).In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7(SLAMF7) and triggering receptor expressed on myeloid cells 1(TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR,and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD73 were significantly lower at day 5 of co-culture than at day 0.CONCLUSION The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.
基金This study was supported by the National Natural Science Foundation of China(Grant No.81870076)the Suzhou Medical Key Discipline Funding Project(Grant No.SZXK201821).
文摘Objective:To investigate the application of peripheral blood triggering receptor expressed on myeloid cells-1(TREM-1)for sequential treatment switching points in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:A total of 120 cases of COPD patients with respiratory failure from June 2017 to December 2018 were randomly divided into two groups:60 cases in the control group and 60 cases in the observation group.The control group received spontaneous breathing trials for 2 h to select the time for non-invasive positive pressure ventilation,while the observation group received peripheral blood TREM-1(≤90.0 pg/mL)to select the time for non-invasive positive pressure ventilation.The stress hormones,clinical pulmonary infection score and vital signs of two groups after 24 h of mechanical ventilation were detected.The treatment time and the adverse reactions of the two groups were recorded.Results:There was no significant difference in rennin,adrenaline,noradrenaline and angiotensin II between two groups(P>0.05).Compared with the control group,the clinical pulmonary infection score was decreased in the observation group(P<0.05).There was no significant difference in heart rate,respiratory rate,pH,partial pressure of carbon dioxide and partial pressure of oxygen between two groups(P>0.05).There was no significant difference in intensive care monitoring time between two groups(P>0.05).Compared with the control group,the observation group had no significant difference in invasive ventilation time and total mechanical ventilation.The time of hospitalization and hospitalization had significantly decreased(P<0.05).There was no significant difference in mortality,ventilator-associated pneumonia and re-intubation between two groups(P>0.05).Conclusion:TREM-1 can be used as a switching point during invasive-noninvasive sequential ventilation for COPD patients with respiratory failure,which can shorten the time of invasive ventilation,total mechanical ventilation and hospitalization.
基金Shandong Province Science and Technology Program (2016GSF201061).
文摘OBJECTIVE To investigate the role of triggering receptor expressed on myeloid cells-2(TREM2) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) model mice with Parkinson disease(PD) and explore the underlying signaling pathway that mediate TREM2 function.METHODS TREM2 adenovirus were stereologically injected into the right striatum.Two weeks later,MPTP was intraperitoneally injected to produce the acute MPTP mouse model of PD.Mice were sacrificed at different time points following MPTP for biochemical or histological study.RESULTS Overexpression of TREM2 remarkably reduced MPTP-induced neuropathology including the dopaminergic neurodegeneration and neuroinflammation in vivo.Further study revealed that TREM2 may inhibit neuroinflammation by negatively regulating the TRAF6/TLR4-mediated activation of the MAPK and NF-κB signaling pathways.CONCLUSION TREM2 may have important neuroprotective effects against PD by critical y modulating neuroinflammatory responses.
文摘Objective: To investigate the correlation of serum soluble triggering receptors expressed on myeloid cells 1 (sTREM-1) content with inflammatory factors and immune function in neonatal infectious pneumonia. Methods: A total of 62 neonates with infectious pneumonia who were treated in Xiaogan Hospital Affiliated to Wuhan University of Science and Technology between July 2016 and September 2017 were selected as pneumonia group, and 50 healthy neonates who were born in this hospital during the same period were selected as normal control group. The differences in serum levels of sTREM-1, inflammatory factors and immunoglobulins were compared between the two groups. Results: Serum sTREM-1 content of pneumonia group was higher than that of normal control group;serum cytokines IL-10, IL-17, PCT and CRP contents were higher than those of normal control group;serum immunoglobulins IgA, IgG and IgM contents were higher than those of normal control group;serum IL-10, IL-17, PCT, CRP, IgA, IgG and IgG contents of pneumonia group of neonates with high serum sTREM-1 content were higher than those of neonates with low serum sTREM-1 content. Conclusion: Serum sTREM-1 content is higher in neonates with infectious pneumonia, which is directly correlated with the inflammatory response and humoral immune function.
文摘Objective: To study the correlation of serum HMGB1 and sTLT-1 contents with oxidative stress response and endothelial injury in patients with ischemic stroke. Methods: The patients who were diagnosed with ischemic stroke in Zhouzhi County People's Hospital between February 2015 and March 2017 were selected as the stroke group of the study, and healthy subjects who received physical examination during the same period were selected as the control group of the study. Serum was collected to determine the contents of HMGB1, sTLT-1, oxidative stress reaction molecules and endothelial injury molecules. Results: Serum HMGB1, sTLT-1, vWF, vWF-cp, sTM, ET-1, D-D, 8-OHdG, LPO and NOS contents of stroke group were significantly higher than those of control group while T-SOD and GSH-Px contents were significantly lower than those of control group;serum T-SOD and GSH-Px contents of stroke patients with high HMBG-1 content were significantly lower than those of stroke patients with low HMBG-1 content while 8-OHdG, LPO and NOS contents were significantly higher than those of stroke patients with low HMBG-1 content;serum vWF, vWF-cp, sTM, ET-1 and D-D contents of stroke patients with high sTLT-1 content were significantly higher than those of stroke patients with low sTLT-1 content. Conclusion: The abnormally elevated HMGB1 and sTLT-1 in serum of patients with ischemic stroke can induce oxidative stress response and aggravate endothelial injury.