Research progress on phenotype and function of microglia / 中国药理学通报

Microglia are the central nervous system's resident myeloid-derived immune cells, which play a major role in the innate and acquired immunological responses of brain. In the maintenance of brain tissue function under both healthy and pathological conditions, microglia take a protective or damaging role, depending on cell phenotypes and functions. The traditional microglia classification of pro- or anti-inflammatory phenotypes refers to the profile of macrophages, hence the term “brain macrophages:has been drawn. More microglia phenotypes are being discovered as new technologies and research methods are developed, and the newly discovered microglia phenotypes are often disease-, brain region-, and function-specific, providing an important foundation for studying the pathological processes underlying the development of specific diseases and developing appropriate interventions. Here, we provide a retrospective review of recent advances in the study of phenotype and function of microglia, and analyze the microglial cell lineage composition and its heterogeneous function.

TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization / 神经科学通报·英文版

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4+ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4+ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.

Research Progress on Mechanisms of Triggeringreceptor Expressed on Myeloid Cells-2 in Cognitive Dysfunction / 中山大学学报(医学科学版)

The neuroimmune system is crucial for the development， aging， and damage of the central nervous system， and has gradually become a research hotspot. Triggeringreceptor expressed on myeloid cells-2 （TREM2） is a transmembrane receptor of the immunoglobulin superfamily and is mainly expressed in the microglia in the central nervous system. An increasing number of studies indicate that TREM2 has great potential to improve cognitive dysfunction related to Alzheimer's disease， vascular dementia， Parkinson's disease， postoperative cognitive impairment， obesity， etc. However， there is a lack of a systematic summary of the specific role of TREM2 in cognitive dysfunction. This paper reviews the progress in the latest research on the related mechanisms of TREM2 in cognitive dysfunction， in order to provide new strategies for the treatment of cognitive dysfunction.

ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.

Impact of lead oxide nanoparticle exposure on the polarization of microglia cells in mouse hippocampus / 中国职业医学

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Mechanism study of chlorogenic acid alleviating macrophage activation / 中国药房

OBJECTIVE To observe the effects of chlorogenic acid on the activation of macrophage induced by lipopolysaccharide （LPS）， and to explore the role of triggering receptors expressed on myeloid cells-2 （TREM2） in the action. METHODS To find a suitable LPS concentration， the cells were cultured with 1， 10 and 100 ng/mL LPS for 24 h. The level of interleukin 6 （IL-6） in the cell culture supernatant and protein expression of inducible nitric oxide synthase （iNOS） in the cells were detected. To search for a suitable chlorogenic acid concentration， the cells were divided into control group， LPS group and three chlorogenic acid （0.01， 0.1 and 1 μmol/L）+LPS groups. The levels of tumor necrosis factor α （TNF-α） and IL-1β in the cell culture supernatant， the protein expressions of iNOS and TREM2 in the cells and cell viability were detected. To observe the effects of TREM2 in chlorogenic acid alleviating macrophage activation， TREM2-small interfering RNA （TREM2-siRNA） was taken to intervene in TREM2 protein expression. The cells were divided into control group， LPS group， chlorogenic acid+LPS group， TREM2-siRNA+chlorogenic acid+LPS group and SC-siRNA+chlorogenic acid+LPS group. After 24 h incubation， the levels of TNF- α and IL-1β in the cell culture supernatant and protein expressions of TREM2， iNOS and nuclear factor κB p65 （NF-κB p65） in the cells were detected. RESULTS 10 ng/mL LPS promoted IL-6 release and increased iNOS protein expression， and 10 ng/mL LPS was taken in the next experiments. Compared with the LPS group， 0.1 μmol/L chlorogenic acid decreased TNF-α jiaji1981@126.com and IL-1β levels， and down-regulated iNOS expression，meanwhile increased TREM2 expression without effect on cell viability， and 0.1 μmol/L chlorogenic acid was taken in the next experiments. Compared with the control group， the protein expressions of iNOS and NF- κB p65 in the LPS group were significantly increased （P＜0.05）； compared with the LPS group， the protein expressions of iNOS and NF- κB p65 in the chlorogenic acid+LPS group were significantly decreased， the protein expressions of TREM2 was significantly increased （P＜ 0.05）； compared with the chlorogenic acid+LPS group， the protein expressions of iNOS and NF-κB p65 of TREM2-siRNA+ chlorogenic acid+LPS group were significantly increased， the protein expressions of TREM2 was significantly decreased （P＜0.05）. TREM2-siRNA could significantly reverse the above effects of chlorogenic acid， while SC-siRNA did not significantly affect the above anti-inflammatory effects of chlorogenic acid. CONCLUSIONS Chlorogenic acid can inhibit the LPS-induced macrophage activation， and its anti-inflammatory may be mediated by TREM2 protein.

The influence of serum triggering receptor expressed on myeloid cells 1 level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome / 中华老年医学杂志

Objective:To study the influence of serum triggering receptor expressed on myeloid cells 1(TREM-1)level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome(ARDS).Methods:A total of 100 elderly patients with sepsis were selected as the research objects.All the patients with sepsis were divided into sepsis ARDS group and sepsis non-ARDS group.General data and TREM-1 level were compared between the two groups.The patients with sepsis ARDS were divided into death group and survival group according to the survival status during the 28-day follow-up.TREM-1 level, acute physiology and chronic health evaluation(APACHE)Ⅱ score and SOFA score were compared between the two groups.The correlation between serum TREM-1 level and procalcitonin(PCT), APACHE Ⅱ score and SOFA score was analyzed.The survival rate of high TREM-1 level group and low TREM-1 level group was compared.Results:The age, white blood cell(WBC), PCT, APACHE Ⅱ score, SOFA score and TREM-1 level of sepsis ARDS patients were significantly higher than those of non-ARDS patients( t=2.722, 6.088, 11.55, 6.889, 4.661, 6.122, all P<0.05). The incidence of sepsis ARDS patients with chronic obstructive pulmonary disease was significantly higher than that of non-ARDS patients( χ2=7.895, P<0.05). Serum TREM-1 level, APACHE Ⅱ score and SOFA score of ARDS patients in death group were significantly higher than those in survival group( t=3.293, 6.173, 4.255, all P<0.05). Serum TREM-1 level was positively correlated with PCT, APACHE Ⅱ score and SOFA score( t=0.553, 0.602, 0.636, P<0.001). The Kaplan-Meier survival curve showed that the survival rate of high TREM-1 level group was significantly lower than that of low TREM-1 level group( χ2=3.999, P=0.036). Cox regression analysis showed that TREM-1 level was a risk factor for the prognosis of ARDS patients with sepsis( HR=1.893, 95% CI: 1.049-3.414). Conclusions:Serum TREM-1 level is significantly increased in elderly patients with sepsis ARDS, which is closely related to the prognosis and can be used as a potential prognostic biomarker.

Expression of serum soluble triggering receptor expressed on myeloid cells 2 in patients with vascular dementia and its relationship with β-amyloid 1-42 and lipoprotein-associated phospholipase 2 / 中华老年医学杂志

Objective:To investigate the expression levels of serum soluble triggering receptor expressed on myeloid cells 2(sTREM2)in patients with vascular dementia(VD)and its relationship with β-amyloid 1-42(Aβ1-42)and lipoprotein-associated phospholipase 2(Lp-PLA2), as well as its value in diagnosis and differential diagnosis.Methods:A total of 152 patients with ischemic stroke receiving routine treatment in our hospital from January 2018 to January 2020 were included and divided into a VD group(n=76)and a non-VD group(n=76)according to evaluation from subsequent visits at 3 months.General data, Mini-Mental State Examination Scale(MMSE), Hachinski Ischemic Scale(HIS)scores, and the levels of biochemical indicators were compared and analyzed for the two groups.Results:There were statistically significant differences in lesion size between the VD group and the non-VD group( P<0.05). The MMSE score in the VD group was significantly lower than that in the non-VD group.The HIS score, serum levels of sTREM2[(3.34±1.18)μg/L and(2.78±1.25)μg/L, t=2.121, P=0.036], Aβ1-42[(93.69±14.45)ng/L and(81.24±14.21)ng/L, t=4.003, P<0.001]and Lp-PLA2 levels[(58.67±14.15)μg/L and(43.18±13.86)μg/L, t=5.096, P<0.001]were significantly higher in patients with VD than in patients without VD( P<0.05). Serum sTREM2 was positively correlated with Aβ1-42( r=0.723, P<0.001)and Lp-PLA2( r=0.714, P<0.001), and Aβ1-42 was positively correlated with Lp-PLA2( r=0.698, P<0.001)in VD patients.The cut-off value, sensitivity, specificity, and area under the curve of serum sTREM2 for differentiating VD from non-VD were 3.96 μg/L, 81.30%, 78.40%, and 0.838, respectively. Conclusions:Serum sTREM2 is abnormally elevated in VD patients, and is significantly correlated with Aβ1-42 and LP-PLA2, thus STREM2 may be an indicator in the differential diagnosis of VD and non-VD.

Relationship between CCL21 and TREM2/DAP12 signaling pathways in spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain / 中华麻醉学杂志

Objective:To evaluate the relationship between CCL21 and triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) signaling pathways in the spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Thirty-two SPF healthy male C57BL/6J mice, weighing 18-22 g, aged 8-10 weeks, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), CCL21 neutralizing antibody group (group anti-CCL21), remifentanil + incisional pain group (group R+ I), and CCL21 neutralizing antibody + remifentanil + incisional pain group (group anti-CCL21+ R+ I).A CCL21 neutralizing antibody 0.3 μg (diluted to 10 μl in normal saline) was intrathecally injected in anti-CCL21 and anti-CCL21+ R+ I groups twice a day.Normal saline 10 μl was intrathecally injected at the same time point twice a day in C and R+ I groups.Fifteen min after intrathecal injection, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at an interval of 15 min in C and anti-CCL21 groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was injected via the caudal vein for 4 consecutive times at an interval of 15 min in R+ I and anti-CCL21+ R+ I groups.The tail-flick latency (TFL) and mechanical paw withdrawal threshold (MWT) were measured at 24 h before remifentanil or normal saline injection (T 0) and 3, 6, 24 and 48 h after stopping injection of remifentanil or normal saline (T 1-4).The mice were sacrificed after the last measurement of pain threshold, and L 4-6 segments of the spinal cord were removed for determination of the expression of TREM2 and DAP12 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction). Results:Compared with group C, TFL was significantly shortened and MWT was decreased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was up-regulated in group R+ I and R+ I+ anti-CCL21 ( P<0.05), and no significant change was found in the parameters mentioned above in group anti-CCL21 ( P>0.05).Compared with group R+ I, TFL was significantly prolonged and MWT was increased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was down-regulated in group anti-CCL21+ R+ I ( P<0.05). Conclusions:CCL21 is involved in remifentanil-induced hyperalgesia by activating TREM2/DAP12 signaling pathways in the spinal dorsal horn of mice with incisional pain.

Progress of tumor-associated myeloid cells in multiple myeloma / 白血病·淋巴瘤

Multiple myeloma (MM) is a kind of hematologic malignancy. Although there are lots of therapies for MM, it is still incurable. Except for the drug-resistance, another important reason for the incurability is the immunosuppressive effect derived from interactions between tumor cells and the bone marrow microenvironment, which makes our body cannot clear resident tumor cells completely. As a vital part in the immunosuppressive microenvironment, tumor-associated myeloid cells (TAMC) play an extremely significant role in the immune escape of MM and become the reason for limiting the effectiveness of immunotherapy, furthermore, TAMC have become potential targets for the treatment of MM. This article reviews the composition and the latest progress of the mechanisms of TAMC in the immune microenvironment of MM.

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.

Progress of myeloid cells in promoting the malignant progression of glioma / 肿瘤研究与临床

Myeloid cells are an important part of glioma's microenvironment. They have strong immune function, mainly composed of glioma related microglia/macrophages and myelogenous suppressor cells. This article reviews the mechanism of myeloid cells in promoting the malignant progression of glioma, and sorts out a number of related pathways, which provides a new direction and thinking for targeted treatment of glioma.

Research advances in the role of myeloid-derived suppressor cells in liver diseases / 临床肝胆病杂志

In recent years, more and more studies have shown that myeloid-derived suppressor cells (MDSCs) participate in the development and progression of various chronic liver diseases including chronic viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver diseases, and liver cancer. As a type of cells derived from bone marrow progenitor cells and immature myeloid cells, MDSCs play an important role in the development, progression, and repair of liver diseases by regulating inflammatory response and the differentiation and function of immune cells. This article reviews the research advances in the association between MDSCs and various liver diseases, in order to provide new thoughts for the clinical diagnosis, prognosis, and treatment of chronic liver diseases.

Advances in chronic liver diseases with abnormal chemokine expression and colorectal cancer liver metastasis / 中国肿瘤临床

The incidence of colorectal cancer (CRC) is increasing rapidly in China. In fact, in 2019, China was the country with the highest CRC case numbers in the world. Specific myeloid cell subsets are recruited into the liver micro-environment via chemokine-receptor axis and facilitate the progression of colorectal liver metastasis(CRLM). In China, many CRC patients suffer concomitant chronic liver diseases, such as chronic hepatitis B (CHB), nonalcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD). Aberrant expression of chemokines is observed in these chronic liver diseases, and some of them have been associated with cancer metastasis. Here, first, we review the recent epidemiological trends of CRC, CHB, NAFLD, and ALD in China, briefly summarizing the abnormal chemokine changes in these chronic liver diseases. Furthermore, we review the potential mechanisms that may explain how different chronic liver diseases facilitate CRLM, focusing on the chemokine-myeloid cell subsets axis, which has been previously reported to be related to CRLM.

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.

Evaluation of the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats

Abstract INTRODUCTION: Sepsis is an important cause of mortality and morbidity, and inflammatory response and oxidative stress play major roles underlying its pathophysiology. Here, we evaluated the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats. METHODS: Twenty-eight adult Sprague Dawley rats were classified into Control (Group 1), Sepsis (Group 2), Sepsis+Cefazolin (Group 3), and Sepsis+Cefazolin+Etanercept (Group 4) groups. Kidney tissue and serum samples were obtained for biochemical and histopathological investigations and examined for the C reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), triggering receptor expressed on myeloid cells (TREM), and malondialdehyde (MDA) levels. RESULTS: The levels of TNF-α, TREM, and MDA in serum and kidney samples were significantly higher in rats from sepsis group than in rats from control group (p < 0.05). Group 3 showed a significant reduction in serum levels of TNF-α, CRP, and TREM as compared with Group 2 (p < 0.05). Serum TNF-α, CRP, TREM, and MDA levels and kidney TNF-α and TREM levels were significantly lower in Group 4 than in Group 2 (p < 0.05). Serum TNF-α and TREM levels in Group 4 were significantly lower than those in Group 3, and histopathological scores were significantly lower in Group 3 and Group 4 than in Group 2 (p < 0.05). Histopathological scores of Group 4 were significantly lower than those of Group 3 (p < 0.05). CONCLUSIONS: Etanercept, a TNF-α inhibitor, may ameliorate sepsis-induced oxidative stress, inflammation, and histopathological damage.

Effects and mechanism of TREM-1 On inflammatory response and lipid metabolism in mice with non-alcoholic fatty liver disease / 中华肝胆外科杂志

0bjective Analysis of the effect of triggering receptor-1 expressed on myeloid cells(TREM-1)in nonalcoholic fatty liver disease(NAFLD)and the mechanism.Methods The oleic acid-treated HepG2 ceils were divided into model group,overexpression group,interference group A,interference group B and negative control group.The mouse model of NAFLD was generated and randomly divided into(nuclear factor-κB)NF-κB inhibition group,protein kinase B(AKT)inhibition group,knockout group A,knockout group B and control group.The expression of inflammatory factors and TREM.1 in liver tissue was detected by PCR,and fat accumulation was detected by oil red O staining.Western blotting was used to detect the expression of TREM-1 and signaling pathway proteins,and HE staining was used to detect liver tissue changes.Results TREM-1 was up.regulated in liver tissue of NAFLD mice J(0.936±0.127)vs.(0.432±0.105)] and in oleic acid-treated HepG2 cells.In oleic acid.treated HepG2 cells.overexpression of TREM-1 increased inflammatory factor expression and increased 1ipid droplets:inhibition of TREM-1 expression decreased inflammatory factor expression.and lipid droplets decreased.Knockout of TREM-1 and inhibition of NF-κB in NAFLD mice reduced hepatocyte inflammatory factor expression and reduced liver damage;knockout of TREM-1 and inhibition of AKT reduced liver tissue lipids and drops accumulate,Conclusions The overexpression of TREM-1 in NAFLD mice liver tissue can regulate inflammatory factor expression and lipid droplets through NF-κB and AKT signal pathway.TREM-1 might be a potential thera-peutic target of NAFLD.

Effects and mechanism of TREM-1 on inflammatory response and lipid metabolism in mice with nonalcoholic fatty liver disease / 中华肝胆外科杂志

Objective@#Analysis of the effect of triggering receptor-1 expressed on myeloid cells (TREM-1) in nonalcoholic fatty liver disease (NAFLD) and the mechanism.@*Methods@#The oleic acid-treated HepG2 cells were divided into model group, overexpression group, interference group A, interference group B and negative control group. The mouse model of NAFLD was generated and randomly divided into (nuclear factor-κB) NF-κB inhibition group, protein kinase B (AKT) inhibition group, knockout group A, knockout group B and control group. The expression of inflammatory factors and TREM-1 in liver tissue was detected by PCR, and fat accumulation was detected by oil red O staining. Western blotting was used to detect the expression of TREM-1 and signaling pathway proteins, and HE staining was used to detect liver tissue changes.@*Results@#TREM-1 was up-regulated in liver tissue of NAFLD mice [(0.936±0.127) vs. (0.432±0.105)] and in oleic acid-treated HepG2 cells. In oleic acid-treated HepG2 cells, overexpression of TREM-1 increased inflammatory factor expression and increased lipid droplets; inhibition of TREM-1 expression decreased inflammatory factor expression, and lipid droplets decreased. Knockout of TREM-1 and inhibition of NF-κB in NAFLD mice reduced hepatocyte inflammatory factor expression and reduced liver damage; knockout of TREM-1 and inhibition of AKT reduced liver tissue lipids and drops accumulate.@*Conclusions@#The overexpression of TREM-1 in NAFLD mice liver tissue can regulate inflammatory factor expression and lipid droplets through NF-κB and AKT signal pathway. TREM-1 might be a potential therapeutic target of NAFLD.

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.

Clinical value of serum new molecular markers in the early diagnosis of sepsis in elderly patients with burns / 中华老年医学杂志

Objective@#To investigate the clinical value of the serum new molecular markers, soluble triggering receptor expressed on myeloid cells-1(sTREM-1)and soluble hemoglobin scavenger receptor(sCD163), in the diagnosis of sepsis in elderly patients with burns.@*Methods@#A total of 58 inpatients with burns from Jun 2017 to June 2018 were enrolled in the study.Patients were divided into three groups: the sepsis group(n=12), the localized infection group(n=21)and the non-infection group(n=29). The levels of sTREM-1 and sCD163 were determined by enzyme-linked immunosorbent assays(ELISAs). The clinical diagnostic value of sTREM-1 and sCD163 was assessed by receiver operating characteristic(ROC)curve analysis.@*Results@#There was a statistically significant difference in the levels of sTREM-1 and sCD163 at day 1 between the three groups(F=20.994 and 38.363, P<0.01). Serum levels of sTREM-1 and sCD163 were higher in the sepsis group than in the localized infection group and the non-infection group.Serum levels of sTREM-1 and sCD163 were higher in the localized infection group than in the non-infection group.Serum levels of sTREM-1 and sCD163 were lower at day 7 than those at day 1 in all groups(F=21.242 and 41.035, P<0.01). Serum sTREM-1 levels were positively correlated with serum sCD163 levels(r=0.609, P=0.000). The AUC of sTREM-1 and sCD163 for the diagnosis of sepsis was 0.880(95%CI: 0.816~0.926).@*Conclusions@#Serum levels of sTREM-1 and sCD163 are elevated with increasing degrees of infection.Monitoring serum sTREM-1 and sCD163 levels is helpful for the diagnosis of sepsis in elderly patients with burns.