Effect of Danzhijiangtang capsule on monocyte chemoattractant protein-1 mRNA expression in newly diagnosed diabetes subclinical vascular lesions

AIM:To investigate the effect of Danzhijiangtang capsule(DJC) on monocyte chemoattractant protein-1(MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus(T2DM) subclinical vascular lesions.METHODS:Sixty-two patients with newly diagnosed T2DM subclinical vascular lesions were randomly divided into a control group and treatment group of 31 cases each.Oral antidiabetic therapy with routine western medicine was conducted in both groups,and the treatment group was additionally treated with DJCs.The treatment course for both groups was 12 wk.Before and after treatment,the total efficiency and traditional Chinese medicine(TCM) syndrome score were calculated.The fasting plasma glucose(FPG),2-h plasma glucose(2hPG),fasting insulin(FINS),insulin resistance index(IRI),hemoglobin(Hb)A1c,blood lipids,and hemorheology indices were determined.In addition,the levels of vascular endothelial growth factors including thrombomodulin(TM),von Willebrand factor(vWF),P-selectin and MCP-1 mRNA were determined.RESULTS:After 12 wk of treatment,the TCM syndrome score was significantly decreased compared to before treatment in both groups.After treatment,FPG,2hPG,HbA1c,FINS,IRI,total cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,whole blood low shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA were significantly improved compared to before treatment in both groups.After treatment,the total efficiency and TCM syndrome score in the treatment group were better than in the control group.FINS,IRI,whole blood high shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA level in the treatment group were significantly reduced after treatment compared with control group.CONCLUSION:DJCs are efficacious in supplementing qi,nourishing yin and invigorating blood circulation,and upregulate MCP-1 mRNA expression in patients with T2DM subclinical vascular lesions.

Analysis of monocyte chemotactic protein-1 gene polymorphism in patients with spontaneous bacterial peritonitis

AIM:To investigate a genetic polymorphism of the monocyte chemotactic protein-1 (MCP-1 ) gene in patients with spontaneous bacterial peritonitis (SBP).METHODS:MCP-1 genotyping was performed in 23 patients with SBP and 83 cirrhotic control patients with non-infected ascites.RESULTS:The frequency of carriers of the G-allele was lower in SBP patients but this difference did not reach statistical significance. However,in the subgroup of patients with alcoholic cirrhosis (n=80),carriers of the G-allele were significantly less frequent in SBP-patients (38.1%) than in cirrhotic controls (67.8%,P=0.021). CONCLUSION:In patients with alcoholic liver cirrhosis,the-2518 MCP-1 genotype AA is a risk factor for the development of SBP.

Molecular detection of monocyte chemotactic protein-1 polymorphism in spontaneous bacterial peritonitis patients

AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).

Effects of Simvastatin on NF-κB-DNA Binding Activity and Monocyte Chemoattractant Protein-1 Expression in a Rabbit Model of Atherosclerosis

To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.

Expression of monocyte chemotactic protein-1/CCL2 in gastric cancer and its relationship with tumor hypoxia

AIM: To investigate the expression and prognostic value of CCL2 in gastric cancer, as well as its relationship with tumor hypoxia.

Plasma monocyte chemotactic protein-1 remains elevated after minimally invasive colorectal cancer resection

AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer(CRC) and benign patients and postoperatively after CRC resection.METHODS: A plasma bank was screened for minimally invasive colorectal cancer resection(MICR) for CRC and benign disease(BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples(postoperative day 7-27) were available. Monocyte chemotactic protein-1(MCP-1) levels(pg/mL) were determined via enzyme linked immuno-absorbent assay. RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level(283.1, CI: 256.0, 294.3) was higher than the BEN group level(227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1(446.3, CI: 418.0, 520.1), postoperative day 3(342.7, CI: 320.4, 377.4), postoperative day 7-13(326.5, CI: 299.4, 354.1), postoperative day 14-20(361.6, CI: 287.8, 407.9), and postoperative day 21-27(318.1, CI: 287.2, 371.6; P < 0.001 for all). CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients(vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.

Malarial pigment enhances heat shock protein-27 in THP-1 cells:new perspectives for in vitro studies on monocyte apoptosis prevention

Objective:To investigate the effect of malarial pigment(hemozoin,HZ) on expression of heat shock proteins(HSPs) and cell viability in human monocytes by using a stable cell line(THP-1 cells).Methods:THP-1 cells were fed with native HZ or treated with pro-apoptotic molecule gliotoxin for 9 h.Thereafter,the protein expression of HSP-27 and HSP-70 was evaluated by western blotting.Alternatively,HZ-fed cells were cultured up to 72 h and cell viability parameters(survival,apoptosis and necrosis rates) were measured by flow cytometric analysis. Results:HZ increased basal protein levels of HSP-27 without altering those of HSP-70 in THP-1 cells,and promoted long-term cell survival without inducing apoptosis.As expected,gliotoxin inhibited HSP-27 protein expression and promoted long-term cell apoptosis.Conclusions: Present data show that HZ prevents cell apoptosis and enhances the expression of anli-apoptotic HSP-27 in THP-1 cells,confirming the previous evidences obtained from HZ-fed immunopurified monocytes.Since the use of a stable cell line is pivotal to perform HSP-27 silencing experiments, monocytic THP-1 cells could be a good candidate line for such an approach,which is heavily required to clarify the role of HSP-27 in survival of impaired HZ-fed monocytes during falciparum malaria.

Expression of Monocyte Chemoattractant Protein-1 in Monocytes and Effects of Native and Oxidized Very Low Density Lipoproteins

Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃，and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.

Monocyte chemotactic protein-1 gene polymorphism and spontaneous bacterial peritonitis

I read with great interest the article by Gbele et al published in issue 44 of World J Gastroenterol 2009.The results of their study indicate that-2518 Monocyte chemotactic protein-1(MCP-1)genotype AA is a risk factor for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.However,there are some items that need to be discussed.

Monocyte chemotactic protein-1 and soluble adhesion molecules as possible prognostic markers of the efficacy of antiviral treatment in chronic hepatitis C

AIM:To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV). METHODS:Concentrations of MCP-1,soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1),sP- selectin,interleukin (IL) 6,and IL10 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0,16,32,48 wk of the therapy, RESULTS:In chronic hepatitis C,before and during the treatment,the serum levels of MCP-1 and sP-selectin in responders were similar to those of healthy subjects.In non- responders (NR),MCP-1 increased in the course of IFNc^+RBV treatment,differences were statistically significant as compared to responders.MCP-1 correlated statistically with the activity of periportal inflammation (r=0.35,P<0.05) but not with staging of liver fibrosis,sICAM-1 positively correlated with inflammatory activity and fibrosis in NR.sP-selectin did not correlate with histological findings in the liver.The MCP-1 correlated with the soluble form of sP-selectin concentrations (r= 6,P<0.001) and with IL-10 level in NR (r=0.4,P<0.05).There was no correlation observed between the concentration of MCP-1 and sICAM-1,IL-6 during the treatment. CONCLUSION:MCP-1 concentration may be a prognostic marker of the efficacy of IFN+RBV therapy in patients with chronic hepatitis C.

Correlation of serum cyclophilin A and monocyte chemoattractant protein-1 levels with carotid atherosclerosis in patients with acute cerebral infarction

Objective:To study the correlation of serum cyclophilin A (CyPA) and monocyte chemoattractant protein-1 (MCP-1) levels with carotid atherosclerosis in patients with acute cerebral infarction.Methods: 106 patients with acute cerebral infarction who were hospitalized in our hospital between July 2011 and August 2015 were selected as observation group, and 50 cases of healthy persons who received physical examination in our hospital during the same period were selected as normal control group. The serum CyPA and MCP-1 contnets in two groups were determined. According to the median of CyPA and MCP-1 contents in observation group, they were divided into high CyPA group and low CyPA group as well as high MCP-1 group and low MCP-1 group, 53 cases in each group. Contents of lipid metabolism indexes and carotid atherosclerosis illness-related indicators were compared between acute cerebral infarction patients with different CyPA and MCP-1 contents.Results:Serum CyPA and MCP-1 contents in observation group were significantly higher than those in control group. Serum TC, LP(a) and LDL-C contents in high CyPA group and high MCP-1 group were higher than those in low CyPA group and low MCP-1 group while HDL-C contents were lower than those in low CyPA group and low MCP-1 group. Serum CysC, Hcy and UA contents in high CyPA group and high MCP-1 group were higher than those in low CyPA group and low MCP-1 group.Conclusion: Serum CyPA and MCP-1 contents in patients with acute cerebral infarction are higher than those in normal population, and the contents of CyPA and MCP-1 are positively correlated with the degree of carotid atherosclerosis.

The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory events,including monocyte/macrophage infiltration in the brain,glial immune activation and release of neurotoxic substances.In these events,astrocytic-derived monocyte chemoattractant protein-1(MCP-1)plays an important role,whose release is elevated by HIV transactivator of transcription(HIV tat)and could be further elevated by opiates.This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat,including the mediating role of mu opioid receptor(MOR)and CCR2 as well as the possible signal transduction pathways within the cells.Finally,it will make some future perspectives on the exact pathways,new receptors and target cells,and the vulnerability to neurodegeneration with HIV and opiates.

Variation of Serum Monocyte Chemoattractant Protein-1 in Patients with Diabetes and Metabolic Syndrome

This study investigated the variation of serum monocyte chemoattractant protein-1（MCP-1） in patients with both diabetes mellitus（DM） and metabolic syndrome（MS）.Based on the International Diabetes Federation（IDF） diagnostic criteria,93 patients enrolled in this study were divided into four groups：normal control（NC）,simple DM,simple MS,and DM plus MS（DM-MS） groups.The main measures included height,weight,waist circumference（WC）,hip circumference,blood pressure,fasting blood glucose,insulin resistance index（HOMA-IR）,serum triglyceride（TG）,HDL-ch,LDL-ch,and MCP-1.The results showed that the serum levels of MCP-1 in the DM-MS group were significantly increased as compared with those in the DM and MS groups（P0.05）,and the increase in the MCP-1 level in the DM group was much higher than in the MS group（P0.05）.The DM-MS group had the highest HOMA-IR levels,followed by MS,DM and NC groups（P0.05）.Correlation tests showed that the association of MCP-1 with age,HDL-ch,or LDL-ch was insignificant,whereas that of MCP-1 with body mass index（BMI）,waist hip rate（WHR）,WC,systolic blood pressure（SBP）,diastolic blood pressure（DBP）,TG,and HOMA-IR was significantly positive.It was concluded that circulating MCP-1 was substantially increased in patients with both DM and MS as compared with that in the patients with DM or MS alone,and the central obese state may contribute to a more vicious proinflammatory condition and insulin resistance in patients with diabetes.

Effect of monocyte chemoattractant protein-1 on chemotactic gene expression by macrophage cell line U937

Objective: To study the chemotactic superfamily genes expression profiling of macrophage line U937 treated with monocyte chemoattractant protein-1 (MCP-1) using gene chip technique. Methods: Total RNA from macrophage line U937 (as control) and U937 with MCP-1 was extracted, made reverse transcript to cDNA and tested with gene expression chip HO2 human. Results: Some chemotactic-related gene expressions were changed in all analyzed genes. Regulated upon activation, normal T cell expressed and secreted (RANTES) was up-regulated over 2-fold and 7 chemotactic-related genes (CCR2, CCR5, CCL16, GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2) were down-regulated over 2-fold in MCP-1 treated U937 cells at mRNA level. Conclusion: MCP-1 can influence some chemokines and receptors expression in macrophage in vitro, in which MCP-1 mainly down-regulates the chemotactic genes expression of those influencing neutrophilic granulocyte (GROβ, GROγ, IL-8 and granulocyte chemotactic protein 2). Another novel finding is that it can also down-regulate the mRNA level of CCR5, which plays a critical role in many disorders and illnesses.

Monocyte chemoattractant protein-1 plays a key role in type 1 diabetes

Type 1 diabetes is an autoimmune dise as e resulting from the selective destruction of β cells in the pa ncreatic islets. In both human and rodent models of type 1 diabetes, the clinica l disease is preceded by a progressive mononuclear cell invasion of the pancreat ic islets (insulitis). In the early stage of insulitis,the major components are monocyte/macrophages, and the recruitment of mononuclear cells is a critical st ep in the pathogenesis of the type 1 diabetes. Studies have revealed that Monocy te chemoattractant protein-1(MCP-1) specifically recruits monocytes/ macrophag es into pancreas and plays an important role in the development of insulitis and diabetes.

Effect of Llinagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy

Objective:To explore the effect of Linagliptin on tumor necrosis factor receptor and monocyte chemoattractant protein-1 in patients with diabetic nephropathy.Methods: A total of 98 patients with diabetic nephropathy admitted to the Hospital from January 2017 to September 2018 were enrolled. The patients were divided into two groups according to the random double-blind method, with 49 cases in each group. The control group was treated with Metformin, whereas the experimental group was treated with Linagliptin plus Metformin. After 3 months of continuous treatment, the renal function [urinary albumin excretion rate, 24 h urine protein quantitation and serum creatinine], glycolipids metabolic levels [glycated hemoglobin, fasting blood glucose, total cholesterol and triglycerides], monocyte chemoattractant protein-1, tumor necrosis factor receptor, high-sensitivity C-reactive protein, and adverse reactions were compared between the two groups.Results:After 3 months of treatment, the levels of UAER, 24 h Upor and Scr in the experimental group were shown to be lower than those in the control group, and the difference was statistically significant. After 3 months of treatment, the levels of HbA1c, FPG, TC and TG in the experimental group were shown to be lower than the control group, and the difference was statistically significant. After 3 months of treatment, the levels of MCP-1, sTNFR1 and hs-CRP in the experimental group were lower than those in the control group, and the difference was statistically significant. There was no significant difference in incidence of adverse reactions between the two groups.Conclusion: For patients with diabetic nephropathy, Linagliptin is with higher safety, which can help improve their glycolipids metabolic levels and renal function, reduce the inflammatory response and the levels of MCP-1 and sTNFR1, and yet incur fewer adverse reactions.

Role of monocytes and macrophages in experimental and human acute liver failure

Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.

MCP-1-2518位点基因多态性对脊柱结核易感性的影响

目的:分析趋化因子单核细胞趋化蛋白-1(MCP-1)启动子区2518基因型频率和等位基因多态性与中国湖南省汉族人群脊柱结核易感性的关系。方法:连续收录2004年12月～2012年8月我院收治的湖南汉族新发脊柱结核患者及健康志愿者,应用聚合酶链式反应(PCR)和DNA直接测序法检测两组患者MCP-1-2518位点的多态性,运用R×C卡方检验比较两组基因型分布频率的差异,计算各比值比(OR)及95%可信区间(CI)。结果:共纳入符合条件的脊柱结核患者334例,健康志愿者336例。MCP-1-2518GG、AG、AA三种基因型在病例组和对照组中的分布频率分别为37.1%、50.3%、12.6%和25.6%、54.2%、20.2%,两组组间比较有显著性差异(P<0.05),其中MCP-1-2518GG基因型的分布频率在脊柱结核人群中显著增高。MCP-1基因-2518 G/A多态位点G、A等位基因频率在病例组为62.3%和37.7%,在对照组为52.7%和47.3%,两组等位基因的分布频率存在统计学差异(P<0.05),-2518G等位基因与脊柱结核发病相关,其OR值为1.483,95%CI为1.193～1.844。结论:在湖南汉族人群中,MCP-1-2518位点GG基因型和G等位基因均可能与脊柱结核的易感性相关。

单核细胞趋化蛋白-1和血管内皮生长因子mRNA在急性甲醇中毒大鼠脑组织的表达

目的观察大鼠急性甲醇中毒后脑组织趋化因子单核细胞趋化蛋白1(MCP-1)及血管内皮生长因子(VEGF)mRNA水平的表达变化.方法健康成年SD大鼠75只,应用通有混合气体(N2O/O2)的密闭有机玻璃箱并灌胃相应剂量甲醇溶液复制急性高剂量甲醇中毒大鼠和急性低剂量甲醇中毒大鼠(n=5).分不同时段(2h,12 h,24 h,3 d,1周)取大鼠右心房静脉血,采用气相色谱法检测大鼠血液的甲醇浓度,取大鼠脑组织进行总RNA提取,经逆转录得cDNA,用SYBRGreen荧光实时定量PCR技术动态定量监测脑组织中MCP-1和VEGF mRNA在急性甲醇中毒后不同时间点表达的变化.结果 (1)甲醇浓度检测结果:低剂量组在2 h、12 h的血液甲醇浓度较生理盐水组显著升高(P<0.05),高剂量组在2 h、12 h、24 h的血液甲醇浓度较低剂量组和生理盐水组显著升高(P<0.05),各组在3 d和1周均未测出甲醇;(2)MCP-1 mRNA表达变化:在甲醇中毒后2 h明显升高,24 h达到高峰,各个时间点与对照组比较均有显著性差异(P<0.05),在2 h,3 d和1周高剂量组高于低剂量组;(3)VEGF mRNA表达变化:在甲醇中毒后2 h明显升高,24 h达到高峰,各个时间点与对照组比较均有显著性差异(P<0.05),在2 h和12 h高剂量组高于低剂量组.结论急性甲醇中毒后,MGP-1和VEGF mRNA的表达显著升高,程度与甲醇中毒剂量有关,可能在脑损伤形成和发展过程中起着重要作用.