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) 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 Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in blo...BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in bloodstream infections,although the reason for this is unclear.AIM To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections.METHODS Transcriptome sequencing was performed on the livers of Fpr2-/-and wild-type(WT)mice.Differentially expressed genes(DEGs)were identified in the Fpr2-/-and WT mice,and the biological functions of DEGs were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Quantitative real time-polymerase chain reaction(qRT-PCR)and western blot(WB)analyses were used to further validate the expression levels of differential genes.Cell counting kit-8 assay was employed to investigate cell survival.The cell cycle detection kit was used to measure the distribution of cell cycles.The Luminex assay was used to analyze cytokine levels in the liver.The serum biochemical indices and the number of neutrophils in the liver were measured,and hepatic histopathological analysis was performed.RESULTS Compared with the WT group,445 DEGs,including 325 upregulated genes and 120 downregulated genes,were identified in the liver of Fpr2-/-mice.The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle.The qRT-PCR analysis confirmed that several key genes(CycA,CycB1,Cdc20,Cdc25c,and Cdk1)involved in the cell cycle had significant changes.The WB analysis confirmed a decrease in the expression of CDK1 protein.WRW4(an antagonist of Fpr2)could inhibit the proliferation of HepG2 cells in a concentration dependent manner,with an increase in the number of cells in the G0/G1 phase,and a decrease in the number of cells in the S phase.Serum alanine aminotransferase levels increased in Fpr2-/-mice.The Luminex assay measurements showed that interleukin(IL)-10 and chemokine(C-X-C motif)ligand(CXCL)-1 levels were significantly reduced in the liver of Fpr2-/-mice.There was no difference in the number of neutrophils,serum C-reactive protein levels,and liver pathology between WT and Fpr2-/-mice.CONCLUSION Fpr2 participates in the regulation of cell cycle and cell proliferation,and affects the expression of IL-10 and CXCL-1,thus playing an important protective role in maintaining liver homeostasis.展开更多
This paper is aimed to study the effect of ADL on expression of ~z-AR and Mz-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect t...This paper is aimed to study the effect of ADL on expression of ~z-AR and Mz-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ~I-AR and Mz-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/（kg.d） ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/（kg.d） ADL groups than in microwave group. So we have a conclusion that the expression of I^z-AR and Mz-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury.展开更多
Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus CO...Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer.Here,we demonstrated that the combination of AG-041R(a CCK-2 receptor antagonist) plus NS-398(a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition,apoptosis induction,down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.(C)2008 Elsevier Ireland Ltd.All rights reserved.展开更多
AIM:To explore the possibility of using the Non-invasive Micro-test Technique(NMT)to investigate the role of Transient Receptor Potential Canonical 1(TRPC1) in regulating Ca 2+ influxes in HL-7702 cells,a normal human...AIM:To explore the possibility of using the Non-invasive Micro-test Technique(NMT)to investigate the role of Transient Receptor Potential Canonical 1(TRPC1) in regulating Ca 2+ influxes in HL-7702 cells,a normal human liver cell line.METHODS:Net Ca 2+ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces,non-invasively.The expression levels of TRPC1 were increased by liposomal transfection,whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction. RESULTS:Ca 2+ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells.They were enhanced by addition of 20μmol/L noradrenalin and inhibited by 100μmol/L LaCl3(a non-selective Ca 2+ channel blocker);5μmol/L nifedipine did not induce any change.Overexpression of TRPC1 caused increased Ca 2+ influx.Five micromoles per liter nifedipine did not inhibit this elevation,whereas 100μmol/L LaCl3 did.CONCLUSION:In HL-7702 cells,there is a type of TRPC1-dependent Ca 2+ channel,which could be detected via NMT and inhibited by La3+.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
Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migra...Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.展开更多
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.
基金the State Key Laboratory of Pathogen and Biosecurity,No.SKLPBS2119 and SKLPBS2212the Medical Science Research Project of Dalian,No.2112015。
文摘BACKGROUND Formyl peptide receptor 2(Fpr2)is an important receptor in host resistance to bacterial infections.In previous studies,we found that the liver of Fpr2-/-mice is the most severely damaged target organ in bloodstream infections,although the reason for this is unclear.AIM To investigate the role of Fpr2 in liver homeostasis and host resistance to bacterial infections.METHODS Transcriptome sequencing was performed on the livers of Fpr2-/-and wild-type(WT)mice.Differentially expressed genes(DEGs)were identified in the Fpr2-/-and WT mice,and the biological functions of DEGs were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Quantitative real time-polymerase chain reaction(qRT-PCR)and western blot(WB)analyses were used to further validate the expression levels of differential genes.Cell counting kit-8 assay was employed to investigate cell survival.The cell cycle detection kit was used to measure the distribution of cell cycles.The Luminex assay was used to analyze cytokine levels in the liver.The serum biochemical indices and the number of neutrophils in the liver were measured,and hepatic histopathological analysis was performed.RESULTS Compared with the WT group,445 DEGs,including 325 upregulated genes and 120 downregulated genes,were identified in the liver of Fpr2-/-mice.The enrichment analysis using GO and KEGG showed that these DEGs were mainly related to cell cycle.The qRT-PCR analysis confirmed that several key genes(CycA,CycB1,Cdc20,Cdc25c,and Cdk1)involved in the cell cycle had significant changes.The WB analysis confirmed a decrease in the expression of CDK1 protein.WRW4(an antagonist of Fpr2)could inhibit the proliferation of HepG2 cells in a concentration dependent manner,with an increase in the number of cells in the G0/G1 phase,and a decrease in the number of cells in the S phase.Serum alanine aminotransferase levels increased in Fpr2-/-mice.The Luminex assay measurements showed that interleukin(IL)-10 and chemokine(C-X-C motif)ligand(CXCL)-1 levels were significantly reduced in the liver of Fpr2-/-mice.There was no difference in the number of neutrophils,serum C-reactive protein levels,and liver pathology between WT and Fpr2-/-mice.CONCLUSION Fpr2 participates in the regulation of cell cycle and cell proliferation,and affects the expression of IL-10 and CXCL-1,thus playing an important protective role in maintaining liver homeostasis.
文摘This paper is aimed to study the effect of ADL on expression of ~z-AR and Mz-AchR in myocardial cells of rats exposed to microwave radiation. Immunohistochemistry, Western blot and image analysis were used to detect the expression of ~I-AR and Mz-AchR in myocardial cells at 7 and 14 d after microwave exposure. The results show that the expression level was higher in microwave exposure group and 0.75 g/（kg.d） ADL group than in sham operation group and significantly lower in 1.5 and 3.0 g/（kg.d） ADL groups than in microwave group. So we have a conclusion that the expression of I^z-AR and Mz-AchR is down-regulated in myocardial cells of rats exposed to microwave radiation. ADL can protect rats against microwave-induced heart tissue injury.
文摘Gastrin and cyclooxygenase-2(COX-2) playimportant roles in the carcinogenesis and progression ofgastric cancer.However,it remains unknown whether the combination of cholecystokinin-2(CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer.Here,we demonstrated that the combination of AG-041R(a CCK-2 receptor antagonist) plus NS-398(a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition,apoptosis induction,down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells.These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.(C)2008 Elsevier Ireland Ltd.All rights reserved.
基金Supported by The National Natural Science Foundation of China,No.30270532 and No.30670774Tsinghua-Yue-Yuen Medical Science Foundation,No.20240000531 and No.20240000547
文摘AIM:To explore the possibility of using the Non-invasive Micro-test Technique(NMT)to investigate the role of Transient Receptor Potential Canonical 1(TRPC1) in regulating Ca 2+ influxes in HL-7702 cells,a normal human liver cell line.METHODS:Net Ca 2+ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces,non-invasively.The expression levels of TRPC1 were increased by liposomal transfection,whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction. RESULTS:Ca 2+ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells.They were enhanced by addition of 20μmol/L noradrenalin and inhibited by 100μmol/L LaCl3(a non-selective Ca 2+ channel blocker);5μmol/L nifedipine did not induce any change.Overexpression of TRPC1 caused increased Ca 2+ influx.Five micromoles per liter nifedipine did not inhibit this elevation,whereas 100μmol/L LaCl3 did.CONCLUSION:In HL-7702 cells,there is a type of TRPC1-dependent Ca 2+ channel,which could be detected via NMT and inhibited by La3+.
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Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.
