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.

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.

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 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.

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 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.

Advanced oxidation protein products induce monocyte chemoattractant protein-1 expression via p38 mitogen-activated protein kinase activation in rat vascular smooth muscle cells

Background Advanced oxidation protein products （AOPPs） are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 （MCP-1） is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells （VSMCs）.

Urotensin Ⅱ promotes monocyte chemoattractant protein-1 expression in aortic adventitial fibroblasts of rat

Background Urotensin Ⅱ （Ull）,a potent vasoconstrictive peptide,is able to stimulate phenotypic differentiation of adventitial fibroblasts.This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 （MCP1） expression in rat aortic adventitial fibroblasts,so as to explore possible mechanisms in the development of vascular inflammation.Methods Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII （1010-10-7 mol/L） and inhibitors of signal transduction pathways for 1 to 24 hours.MCP-1 mRNA and protein expression and secretion were determined by RT-PCR,Western blotting analysis and enzyme-linked immunosorbent assay （ELISA）,respectively.Results UII dose-and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells,with maximal effect at 10-8 mol/L at 3 hours for mRNA expression,24 hours for protein expression in the cells,and 12 hours for protein secretion from the cells.Furthermore,the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411,Rho kinase inhibitor Y27632,protein kinase C （PKC） inhibitor H7,mitogen-activated protein kinase inhibitor PD98059,calcineurin inhibitor cyclosporine A,and the Ca2＋channel blocker nicardipine.Conclusion UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase,PKC,mitogen-activated protein kinase,calcineurin and Ca2＋ channel signal transduction,thus contributing to adventitial inflammation.

Effects of Wenxiao Decoction(稳消方) on the Expression of Interleukin-6,Intercellular Adhesion Molecular-1and Monocyte Chemoattractant Protein-1 in Experimental Atherosclerotic Rabbits

Objective： To observe the effects of different doses of Wenxiao Decoction （稳消方） on the expression of interleukin-6 （IL-6）, intercellular adhesion molecule-1 （ICAM-1）, and monocyte chemoattractant protein-1 （MCP-1） in experimental atherosclerotic rabbits and to explore the mechanism by which it alleviates atherosclerosis. Methods： Sixty New Zealand rabbits were randomly divided into six groups： a blank group, a model group, a Simvastatin group, and high-, medium-, and low-dosage Wenxiao Decoction groups. Except for those in the blank group, all rabbits were fed with a high-cholesterol diet. Carotid atherosclerosis was established by balloon-induced carotid artery endothelium injury in conjunction with the high-cholesterol diet. After 8 weeks, all animals were euthanized to evaluate levels of IL-6 and ICAM-1 expressions （by enzyme linked immunosorbent assay） and of MCP-1 （by immunohistochemistry staining）. Results： The expressions of IL-6, ICAM-1, and MCP-1 were significantly increased in all groups except the blank group （P〈0.05）. However, the rabbits in the Wenxiao Decoction groups and the Simvastatin group showed significantly lower levels of IL-6, ICAM-1, and MCP-1 expression than those in the model group （P〈0.05）. The expressions of IL-6, ICAM-1, and MCP-1 in the high- dosage Wenxiao Decoction group and the Simvastatin group were lower than those in the low-dosage Wenxiao Decoction group （P〈0.05）. The expression of MCP-1 in medium-dosage Wenxiao Decoction group was lower than that in the low-dosage group （P〈0.05）. Conclusions： High, medium, and low doses of Wenxiao Decoction can inhibit the expressions of IL-6, ICAM-1, and MCP-1, which may prevent and stabilize atherosclerotic plaques. There may be a direct relationship between dosage and therapeutic efficacy of Wenxiao Decoction.

NANOPARTICLE AS A NEW GENE TRANSFERRING VECTOR IN SPECIFIC EXPRESSION GENE

Objective. To evaluate the possibility and efficiency of nanoparticle as a new vector in specific gene transference.Methods. Nanoparticle-DNA complex was prepared with Poly- dl-lactic-co-glycolic acid (PLGA) bearing anti-sense monocyte chemotactic protein-1 (A-MCP-l), a specific expression gene, and the package efficiency, release progress in vitro, and the size of the complex were determined. The possibility of the new vector was evaluated with genomic DNA PCR by transferring gene into cultured smooth muscle cells (SMC), cationic lipids as a control. For study in vivo, jugular vein-to-artery bypass grafting procedures were performed on 20 New Zealand white rabbits, of which 6 grafts were transferred with nanoparticle-A-MCP-1 (200 μg), 6 with A - MCP-1 (200 μ g) by cationic liposome, 4 with LNCX plasmid, and 4 as control. Fourteen days after the grafts were harvested, the expression of A-MCP-l and its effect on MCP-1 in vein grafts were detected by dot blot, and the morphologic evaluation of grafts was performed.Results. The package efficiency of the nanoparticle-DNA complex was 0. 9% , release progress in vitro lasted 2 weeks, and the size ranged from 150 to 300nm. SMC genomic DNA PCR showed that A-MCP-l gene could be successfully transfected into cells by nanoparticle. The study in vivo indicated that A-MCP-l mRNA was expressed in both local gene delivery groups, nanoparticle and liposome, meanwhile, MCP-1 expression in vein grafts was significantly inhibited and neointimal hyperplasia was notably reduced.Conclusion. Nanoparticle can act as a vector to transfect specific gene.

Expression of monocyte chemoattractant protein-1 in the pancreas of mice

Background Type 1 diabetes has been recognized as an organ specific autoimmune disease owing to the immune destruction of pancreatic islet β cells in genetically susceptible individuals. In both human and rodent models of type 1 diabetes, such as nonobese diabetic （NOD） mice, biobreeding rats, the disease has a distinct stage characterized by immune cells infiltrating in the pancreas （insulitis）. The major populations of infiltrating cells are macrophages and T lymphocytes. Therefore, immune cell infiltration of pancreatic islets may be a crucial step in the pathogenesis of type 1 diabetes. Monocyte chemoattractant protein-1 can specifically attract monocytes in vivo. Interferon induced protein-10 has chemoattractant effects on the activated lymphocytes. In this study, we analysed the expression of monocyte chemoattractant protein-1 in the pancreas of mice and interferon inducible protein-10 mRNA in the pancreas of NOD mice, and discussed their possible role in the pathogenesis of type 1 diabetes. Methods The immunohistochemical method and immunoelectronmicroscopy were used to evaluate the expression of monocyte chemoattractant protein-1 in the pancreas of NOD mice and BALB/c mice. RT-PCR was used to evaluate the expression of monocyte chemoattractant protein-1 and interferon inducible protein mRNA in NOD mice. Results Monocyte chemoattractant protein-1 was positive in the pancreas of NOD mice, whereas negative in the pancreas of BALB/C mice. RT-PCR showed that monocyte chemoattractant protein-1 and interferon inducible protein-10 mRNA could be found in the pancreas of NOD mice. Immunoelectronmicroscopy demonstrated that monocyte chemoattractant protein-1 was produced by β cells and stored in the cytoplasm of the cells. Conclusions Pancreatic islet β cells produce monocyte chemoattractantprotein-1 in NOD mice. Monocyte chemoattractant protein-1 may play an important part in the pathogenesis of type 1 diabetes by attracting monocytes/macrophages to infiltrate pancreatic islets.

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.

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).

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.

MCPIP1和TRAF6水平与肾细胞癌患者远端转移风险及预后的关系

目的探讨单核细胞趋化蛋白-1诱导蛋白-1(MCPIP1)和肿瘤坏死因子受体相关因子6(TRAF6)水平与肾细胞癌(RCC)患者远端转移风险及预后的关系。方法选取2017年3月至2020年4月河北省秦皇岛市第二医院收治的223例RCC患者作为研究对象,根据是否发生远端转移将患者分为远端转移组(69例)和无远端转移组(154例)。比较远端转移组和无远端转移组临床资料。以RCC患者血清MCPIP1和TRAF6平均值为临界值,将患者分为MCPIP1高表达组、MCPIP1低表达组和TRAF6高表达组、TRAF6低表达组。采用Pearson相关分析RCC患者血清MCPIP1、TRAF6水平之间及二者与碱性磷酸酶水平的相关性。采用多因素Logistic回归分析RCC患者发生远端转移的危险因素。绘制受试者工作特征(ROC)曲线分析血清MCPIP1、TRAF6对RCC患者发生远端转移的诊断价值。采用Kaplan-Meier分析血清MCPIP1和TRAF6水平与RCC患者预后的关系。结果远端转移组血清MCPIP1水平低于无远端转移组,TRAF6水平高于无远端转移组,差异均有统计学意义(P<0.05)。远端转移组和无远端转移组TNM分期、碱性磷酸酶水平比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,MCPIP1水平降低、TRAF6水平升高、TNM分期为Ⅲ+Ⅳ期、碱性磷酸酶水平升高为RCC患者发生远端转移的危险因素(P<0.05)。ROC曲线分析结果显示,2项指标联合诊断RCC患者发生远端转移的曲线下面积(AUC)为0.940,显著高于单项检测的AUC(Z_(MCPIP1-联合)=2.217,P=0.027;Z_(TRAF6-联合)=5.481,P<0.001)。Pearson相关分析结果显示,RCC患者血清MCPIP1水平和TRAF6水平呈显著负相关(r=-0.459,P<0.001),血清MCPIP1水平与碱性磷酸酶水平呈负相关(r=-0.443,P<0.001),TRAF6水平与碱性磷酸酶水平呈正相关(r=0.471,P<0.05)。Kaplan-Meier曲线分析结果表明,MCPIP1高表达组3年累积生存率显著高于MCPIP1低表达组(χ^(2)=12.625,P<0.001),TRAF6高表达组3年累积生存率显著低于TRAF6低表达组(χ^(2)=10.128,P=0.001)。结论RCC转移患者血清MCPIP1水平降低,TRAF6水平升高,与发生RCC转移和预后不良有关。

Association of NFKB1 gene polymorphism (rs28362491) with levels of inflammatory biomarkers and susceptibility to diabetic nephropathy in Asian Indians

AIM To investigate the association of NFKB1 gene-94 ATTG insertion/deletion(rs28362491) polymorphism with inflammatory markers and risk of diabetic nephropathy in Asian Indians.METHODS A total of 300 subjects were recruited(100 each), normoglycemic,(NG); type 2 diabetes mellitus(T2DM) without any complications(DM) and T2 DM with diabetic nephropathy [DM-chronic renal disease(CRD)]. Analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism and ELISA. Pearson's correlation, analysis of variance and logistic regression wereused for statistical analysis.RESULTS The allelic frequencies of-94 ATTG insertion/deletion were 0.655/0.345(NG), 0.62/0.38(DM) and 0.775/0.225(DM-CRD). The-94 ATTG ins allele was associated with significantly increased levels of urinary monocyte chemoattractant protein-1(u MCP-1); u MCP-1(P = 0.026) and plasma tumor necrosis factor-alpha(TNF-α); TNF-α(P = 0.030) and almost doubled the risk of diabetic nephropathy(OR = 1.91, 95%CI: 1.080-3.386, P = 0.025).CONCLUSION-94 ATTG ins/ins polymorphism might be associated with increased risk of developing nephropathy in Asian Indian subjects with diabetes mellitus.

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.