Assessment of circulating MCP-1 level and 2518A>G gene polymorphism in systemic lupus erythematosus / Avaliação do nível de MCP-1 circulante e polimorfismo do gene 2518A> G no lúpus eritematoso sistêmico

Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE). This study aims to investigate the possible role of a functional polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene and MCP-1 blood level in the diagnosis of LN and in correlating the MCP-1 blood levels with disease activity. The study included 56 SLE patients and 56 controls. All the SLE patients suffered from LN. An analysis of MCP-1 gene polymorphism by polymerase chain reaction was performed followed by restriction fragment length polymorphism (PCR-RFLP) analysis and MCP-1 blood level was determined using the ELISA technique. Calculation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was performed. Serologic tests included the determination of antinuclear antibody (ANA) and anti-double-stranded (ds) DNA antibodies, Complement C3 and C4 levels. A significant increase in the frequency of genotype A/G and a decrease in the frequency of genotype A/A were found among patients with active LN compared to inactive LN. There was a statistically significant difference in the blood level of MCP-1 between LN patients and controls. Also, MCP-1 blood levels were significantly higher in active LN patients than inactive LN. A significant positive linear correlation was detected between MCP-1 blood level and SLEDAI, creatinine, and 24 hours protein in LN patients. These results suggest that an A/G genotype together with the measurement of the blood level of MCP-1 can be a useful tool for detection and follow up of active LN.

A nefrite do lúpus (LN) é um dos principais contribuintes para a morbidade e mortalidade em pacientes com o Lúpus Eritematoso Sistémico (LES). Este estudo tem como objetivo investigar o possível papel de um polimorfismo funcional na região reguladora do gene da proteína quimioatraente de monócitos-1 (MCP-1) e do nível sanguíneo de MCP-1 no diagnóstico de LN e na correlação do sangue de MCP-1 níveis com atividade da doença. O estudo incluiu 56 pacientes com LES e 56 controles. Todos os pacientes com LES sofriam de LN. Uma análise do polimorfismo do gene MCP-1 por reação em cadeia da polimerase foi realizada seguida pela análise do polimorfismo do comprimento do fragmento de restrição (PCR-RFLP) e o nível sanguíneo do MCP-1 foi determinado pela técnica ELISA. O cálculo do índice de atividade da doença sistêmica do lúpus eritematoso (SLEDAI) foi realizado. Os testes sorológicos incluíram a determinação de anticorpos antinucleares (ANA) e anticorpos anti-DNA de fita dupla (ds), níveis de Complemento C3 e C4. Um aumento significativo na frequência do genótipo A/G e uma diminuição na frequência do genótipo A/A foram encontrados entre os pacientes com LN ativo em comparação com o LN inativo. Houve uma diferença estatisticamente significante no nível sanguíneo de MCP-1 entre pacientes com LN e controles. Além disso, os níveis sanguíneos de MCP-1 foram significativamente mais altos em pacientes com LN ativo do que com LN inativo. Uma correlação linear positiva significativa foi detectada entre o nível sanguíneo de MCP-1 e SLEDAI, creatinina e proteína de 24 horas em pacientes com LN. Esses resultados sugerem que um genótipo A/G, juntamente com a medição do nível sanguíneo de MCP-1, pode ser uma ferramenta útil para a detecção e acompanhamento do LN ativo

IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease / Polimorfismos IL-17A, MCP-1, CCR-2 e ABCA1 em crianças com doença hepática gordurosa não alcoólica

Abstract Objective: The prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease. Methods: The study recruited 186 obese children aged 10 -17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. Results: No difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p < 0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio [OR] 2.05, 95% confidence interval: 1.12 -3.77, p = 0.02). Conclusions: The findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children.

Resumo Objetivo: A prevalência de doença hepática gordurosa não alcoólica em crianças aumentou significativamente devido à epidemia de obesidade infantil em todo o mundo nas últimas duas décadas. A doença hepática gordurosa não alcoólica está intimamente ligada ao estilo de vida sedentário, ao aumento do índice de massa corporal e à adiposidade visceral. Além disso, variações genéticas individuais também têm um papel no desenvolvimento e na progressão da doença hepática gordurosa não alcoólica. O objetivo deste estudo foi investigar os polimorfismos genéticos MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313) e IL-17A (-197 G/A) (rs2275913) em crianças turcas obesas com doença hepática gordurosa não alcoólica. Métodos: O estudo recrutou 186 crianças obesas entre 10 e 17 anos, inclusive 101 crianças com doença hepática gordurosa não alcoólica e 85 crianças sem doença hepática gordurosa não alcoólica. Medidas antropométricas, resistência à insulina, painel hepático, perfil lipídico, exame ultrassonográfico do fígado e genotipagem de quatro variantes foram feitos. Resultados: Nenhuma diferença foi encontrada entre os grupos em relação à idade e sexo, índice de massa corporal, relação cintura/quadril ou proporção de gordura corporal. Além dos níveis elevados de ALT, os níveis de AST e GGT foram significativamente maiores no grupo doença hepática gordurosa não alcoólica em comparação com o grupo não doença hepática gordurosa não alcoólica (p < 0,05). O alelo A de IL-17A (-197 G/A) (rs2275913) foi associado à doença hepática gordurosa não alcoólica (odds ratio [OR] 2,05, intervalo de confiança de 95%: 1,12-3,77, p = 0,02). Conclusões: Os achados deste estudo sugerem que pode haver uma associação entre o polimorfismo IL-17A (-197 G/A) (rs2275913) e o desenvolvimento da doença hepática gordurosa não alcoólica em crianças turcas obesas.

Antagonistic effects of extracts from Artemisia rupetris L. and Leontopodium leontopodioides to CC chemokine receptor 2b (CCR2b) / 中国天然药物

The present study was designed to establish a suitable assay to explore CCR2b receptor antagonists from the natural products of Artemisia rupetris and Leontopodium leontopodioides. An aequorin assay was developed as a cell-based assay suitable for 384-well microplate and used for screening CCR2b receptor antagonists from natural products. Through establishing suitable conditions, the assay was shown to be suitable for screening of CCR2b receptor antagonists. Seven compounds were identified in preliminary screening. Five of them showed evident dose-response relationship in secondary screening. The structure-activity relationship study suggested that 7-position hydroxyl group of flavonoids was necessary, a polar group should be introduced on the 3-position, and the substituents on 2-position benzene ring of flavonoids have little influence on the potentency of the inhibition activity on CCR2b receptor. The ortho-position dihydroxyl structure in quinic acid compounds may be important. In conclusion, Compounds HR-1, 5, 7, and AR-20, 35 showed activity as antagonist of CCR2b receptor, which shed lights on the development of novel drugs as CCR2b receptor antagonists for preventing inflammation related diseases.

Progress on Hypoxic-ischemic Brain Damage Associated with CCR2 and CCL2 / 法医学杂志

Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD.

The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

BACKGROUND: Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented. RESULTS: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C-C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model. CONCLUSIONS: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.

Association of CCR2 gene rs1799864 polymorphism with hemophagocytic lymphohistiocytosis in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between rs1799864 single nucleotide polymorphism (SNP) of the C-C chemokine receptor 2 (CCR2) gene and susceptibility of hemophagocytic lymphohistiocytosis (HLH) in children.</p><p><b>METHODS</b>The clinical and laboratory data of 86 children diagnosed with HLH between January 2007 and December 2013 were retrospectively reviewed. The CCR2 gene rs1799864 was genotyped by SNaPshot technique in 86 HLH children and 128 healthy controls. The genotypic and allelic frequencies in the two groups were comparatively analyzed.</p><p><b>RESULTS</b>No significant difference either in genotypic or allelic frequencies of rs1799864 polymorphism of the CCR2 gene was observed between HLH patients and controls (P>0.05), but there were significant differences in the age of onset and the periods of temperature and platelet returning to normal after treatment (P<0.05).</p><p><b>CONCLUSIONS</b>There is no association between CCR2 gene rs1799864 polymorphism and the risk for HLH in children. However, the genotypic differences of this polymorphism might be associated with clinical characteristics and prognosis of HLH.</p>

Expression of monocyte chemotactic protein-1 and its receptor in sudden coronary death / 法医学杂志

OBJECTIVE@#To investigate the expression of monocyte chemotactic protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR-2) in coronary atherosclerosis plaques between sidden coronary death (SCD) and non-SCD. Methods The expression levels of MCP-1 and CCR-2 in SCD group, coronary atherosclerosis group (non-SCD), control group (normal coronary artery) were detected by immunohistochemistry.@*RESULTS@#Positive rates of MCP-1 among the three groups were 78%, 47%, and 0%, respectively, with significant expressing differences between each two groups (P<0.05). Positive rates of CCR-2 among three groups were 72%, 47%, and 0%, respectively, with significant expressing differences between the SCD group and coronary atherosclerosis group as well as between the SCD group and control group (P<0.05), but with no significant expressing difference between coronary atherosclerosis group and control group (P>0.05).@*CONCLUSION@#Overexpression of MCP-1 and CCR-2 in coronary atherosclerotic plaques is closely correlated with SCD.

Role of transient receptor potential vanilloid type 1 and C-C chemokine receptor 2 in renal injury induced by salt-sensitive hype / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the effects of transient receptor potential vanilloid type 1 (TRPV1) channel ablation and a chemokine receptor 2 (CCR2) antagonist on salt-sensitive hypertension-induced renal injury.</p><p><b>METHODS</b>Wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks with or without a CCR2 antagonist, RS504393 (n=8 for all the 4 groups). Sham WT and TRPV1(-/-) mice (both n=7) underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin, 8-isoprostane and creatinine clearance for 24 hours were assayed during the experimental period and at the end of the 4-week treatment. The morphological analysis was performed in renal histological sections, including glomerulosclerosis, tubulointerstitial injury, and monocyte/macrophage infiltration.</p><p><b>RESULTS</b>Compared to the corresponding control mice, DOCA-salt treatment in both WT and TRPV1(-/-) mice led to increased systolic blood pressure (SBP), enhanced urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, increased glomerulosclerosis and tubulointerstitial injury associated with enhanced monocyte/macrophage infiltration (all P<0.05), all of which were much more severe in TRPV1(-/-) mice compared to WT mice with the exception of blood pressure (all P<0.05). RS5043943 attenuated DOCA-salt-induced changes in renal function and morphology in WT and TRPV1(-/-) mice (all P<0.05). There was no difference in blood pressure among DOCA-salt WT and TRPV1(-/-) mice with or without RS505393 with the exception of sham WT and TRPV1(-/-) mice (all P>0.05).</p><p><b>CONCLUSIONS</b>CCR2 antagonist inhibits DOCA-salt-induced renal injury and monocyte/macrophage infiltration in WT and TRPV1(-/-) mice with the greater in the latter strain. Activation of TRPV1 attenuates salt-sensitive hypertension-induced renal injury possibly via inhibition of CCR2-induced monocyte/macrophage infiltration.</p>

CCL2/CCR2 signaling activation contributes to tooth movement pain / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To test the hypothesis that the CCL2/CCR2 signaling pathway plays an important role in pain induced by experimental tooth movement.</p><p><b>METHODS</b>Male Sprague- Dawley rats weighing between 200 and 300 g were used in this study. Expression of CCL2/CCR2 in the trigeminal ganglion (TG) was determined by Western blotting 0 h, 4 h, 1 d, 3 d, 5 d, 7 d after tooth movement. Localization of the CCL2 was revealed by immunohistochemistry. Changes in body weight, nocifensive behaviors, and the effects of CCL2/CCR2 antagonists on these changes in pain behaviors were evaluated. Exogenous CCL2 was injected into periodontal tissues and added to TG neurons in culture and the resulting c-fos expression and pain responses were detected. In addition, the expression and cellular localization of CCL2 in the medullary dorsal horn (MDH) was determined by immunohistochemistry 3 d and 14 d after tooth movement.</p><p><b>RESULTS</b>Experimental tooth movement led to a statistically significant increase in CCL2/CCR2 expression at the protein level from day 3 to 7 after application of force initiating tooth movement.When compared with control group (1.000 ± 0.000), CCL2 increased to (2.620 ± 0.128), (3.300 ± 0.197) and (1.740 ± 1.290) at day 3, 5 and 7 respectively, which were statistically significant (P < 0.05). CCR2 expression levels were (1.636 ± 0.061) and (1.766 ± 0.126) compared with that in control group (1.000 ± 0.000) at day 3 and 5 respectively with statistical significance (P < 0.05). Both of them peaked on day 5 (3.3 and 1.8 time compared to control group). Application of recombinant CCL2 led to the up-regulation of c-fos expression in vivo and in vitro, and triggered a corresponding nocifensive behavior in rats. The magnitude of the nocifensive behavior could be reduced by a CCR2 antagonist, and by CCL2 neutralizing antibody. Furthermore, we found a significant increase in the expression of CCL2, corresponding well to the up-regulation of the time spent on nocifensive behaviors after ETM. In addition, CCL2 was up-regulated in TG neurons and astrocytes in Vc.</p><p><b>CONCLUSIONS</b>The CCL2/CCR2 axis was modulated by experimental tooth movement and involved in the development of tooth movement pain, and thus palyed an important role in orthodontic pain mechanism.</p>

Effects of monocyte chemotactic protein-3 on ICAM-1, VCAM-1, TF, and TFPI expression and apoptosis in human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of monocyte chemotactic protein-3 (MCP-3) on the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tissue factor (TF, and tissue factor pathway inhibitor (TFPI) and cell apoptosis in human umbilical vein endothelial cells (HUVECs).</p><p><b>METHODS</b>Cultured HUVECs were treated with MCP-3 at the optimal concentration determined previously 1 h after treatments with or without MCP-3 antibody (20 ng/ml), PI3K inhibitor, or LY-294002 (5 mmol/ml). The expressions of ICAM-1, VCAM-1, TF and TFPI were analyzed using RT-PCR and Western blot after the treatments. MCP-3 mRNA and protein expressions were detected in HUVECs exposed to 50 µg/ml ox-LDL for 24 h. The cell apoptosis and caspase-3 protein production in HUVECs treated with MCP-3 or with MCP-3 plus CCR2 antagonist for 24 h and 48 h were evaluated by flow cytometry and Western blotting.</p><p><b>RESULTS</b>At the optimal concentration of 0.3 ng/ml, MCP-3 treatment for 24 h caused significantly increased ICAM-1, VCAM-1, and TF expressions with lowered expression of TFPI in HUVECs (P<0.05), and such effects were significantly inhibited by the application of MCP-3 antibody, PI3K inhibitor, or LY-294002 (P<0.05). Ox-LDL exposure significantly increased the expression of MCP-3 in HUVECs (P<0.05). HUVECs showed a significantly increased apoptosis rate after treatment with MCP-3 or with MCP-3 plus CCR2 antagonist (P<0.05), and the apoptosis rate increased significantly as the treatment time prolonged (P<0.05); caspase-3 protein expression in the cells showed a similar pattern of alterations following the treatments.</p><p><b>CONCLUSION</b>ox-LDL can induce MCP-3 expression in HUVECs. MCP-3 induces apoptosis of HUVECs and significantly affects the cellular function partially through the PI3K signaling pathway.</p>

Role of chemokine receptor 2 in renal damage induced by deoxycorticosterone acetate-salt hypertension / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the role of chemokine receptor 2 (CCR2) in the development of salt-sensitive hypertension-induced renal damage.</p><p><b>METHODS</b>We investigated the renal damage induced by uninephrectomy and deoxycorticosterone acetate (DOCA)-salt in mice treated with or without a selective CCR2 antagonist RS504393 for 4 weeks. Sham mice underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration were measured.</p><p><b>RESULTS</b>DOCA-salt treatment led to increased systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, decreased creatinine clearance, glomerulosclerosis, renal tubulointerstitial injury, and renal monocyte/macrophage infiltration compared with the sham mice (P<0.05). All of them were prevented by CCR2 inhibition (P<0.05).</p><p><b>CONCLUSION</b>Blockade of CCR2 prevents renal damage induced by DOCA-salt treatment, suggesting that CCR2-mediated monocyte/macrophage infiltration may contribute to salt-sensitive hypertension-induced renal injury.</p>

Effect of Porphyromonas gingivalis lipopolysacchearide on the expression of CC chemokine receptor 2 in monocytes / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Porphyromonas gingivalis lipopolysacchearide (Pg-LPS) on the expression of CC chemokine receptor 2 (CCR2) in THP-1 monocyte and to explore the relationship between periodontitis and cardiovascular disease in molecular level.</p><p><b>METHODS</b>THP-1 monocytes were incubated with different concentrations of Pg-LPS (10, 100, 1000 µg/L) for 1, 4 and 24 h respectively, then flow cytometry and reverse transcription-PCR were adopted to determine cell surface protein levels and mRNA levels of CCR2.</p><p><b>RESULTS</b>The protein levels and mRNA levels of CCR2 were higher in all experiment groups of 1 h and 4 h than that in the control group (P < 0.05) , except the protein expression of CCR2 in T1 group of 1 h (55.74 ± 0.96) . The protein expression (52.56 ± 0.61, 40.98 ± 0.86, 26.50 ± 0.67) and mRNA levels (0.095 ± 0.006,0.070 ± 0.004,0.046 ± 0.004) of CCR2 were lower in all experiment groups than that in the control group (56.99 ± 0.44,0.104 ± 0.003) at 24 h (P < 0.05) . The protein levels and mRNA levels of CCR2 were increased in all experiment groups at 4 h and reduced at 24 h (P < 0.05).</p><p><b>CONCLUSIONS</b>Pg-LPS can upregulate CCR2 expression on THP-1 monocyte surface in concentration dependent manner in early stage, promoting the monocyte chemoattractant. Periodontitis may promote atherosclerosis by enhancing monocyte chemoattractant through periodontal pathogens.</p>

Association of chemokines and their receptors genes polymorphisms with risk of myocardial infarction / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of variations in chemokines (CCL5, CCL2), chemokine receptor (CCR5 and CCR2) genes with susceptibility to myocardial infarction (MI) through a case-control study.</p><p><b>METHODS</b>Genotypes of patients with MI (n = 634) were compared with those of controls (n = 601). Genetic polymorphisms of CCL5 rs2107538 (-403G > A), CCL2 rs1024611 (-2518A > G), CCR5 rs333 ( δ 32 ins or del) and CCR2 rs1799864 (190G > A) of 1235 individuals were determined with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Particular genotypes were confirmed with DNA sequencing.</p><p><b>RESULTS</b>No subject was found to carry the CCR5 - δ 32 allele. No association was found between CCL2 rs1024611 and CCR2 rs1799864 polymorphisms and MI. For CCL5 rs2107538 polymorphism, the A allele has occurred at a higher frequency in MI patients than controls, and its AA genotype has been associated with a significantly increased risk of MI independent of conventional risk factors (OR = 3.346, 95%CI = 1.938-5.775, P < 0.01, AA vs. GG). Further analysis indicated that MI patients had significantly more A-403 - A-2518 haplotype (CCL5 -403G > A and CCL2 -2518A > G, 21.8% vs. 26.6%, OR = 1.229, 95%CI = 1.012-1.493, P = 0.038) and AA or AA genotype (CCL5 -403G > A - CCL2 -2518A > G, 5.0% vs. 12.1%, OR = 3.245, 95%CI = 1.780-5.914, P < 0.01).</p><p><b>CONCLUSION</b>Although our data dose not support an association between CCL2 rs1024611, CCR2 rs1799864 and CCR5 rs333 polymorphisms and MI, genetic variation in CCL5 gene may still be a useful marker for assessing susceptibility to MI in ethnic Han Chinese population.</p>

KR-31543 reduces the production of proinflammatory molecules in human endothelial cells and monocytes and attenuates atherosclerosis in mouse model

KR-31543, (2S, 3R, 4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethyoxymethyl-3-hydroxy-2-methyl-2H-1-benz opyran is a new neuroprotective agent for ischemia-reperfusion damage. It has also been reported that KR-31543 has protective effects on lipid peroxidation and H2O2-induced reactive oxygen species production. In this study, we investigated the anti-inflammatory and anti-atherogenic properties of KR-31543. We observed that KR-31543 treatment reduced the production of MCP-1, IL-8, and VCAM-1 in HUVECs, and of MCP-1 and IL-6 in THP-1 human monocytes. We also examined the effect of KR-31543 on monocytes migration in vitro. KR-31543 treatment effectively reduced the migration of THP-1 human monocytes to the HUVEC monolayer in a dose-dependent manner. We next examined the effects of this compound on atherogenesis in LDL receptor deficient (Ldlr-/-) mice. After 10 weeks of western diet, the formation of atherosclerotic lesion in aorta was reduced in the KR-31543-treated group compared to the control group. The accumulation of macrophages in lesion was also reduced in KR-31543 treated group. However, the plasma levels of total cholesterol, HDL, LDL, and triglyceride were not affected by KR-31543 treatment. Taken together, these results show that KR-31543 has anti-inflammatory properties on human monocytes and endothelial cells, and inhibits fatty streak lesion formation in mouse model of atherosclerosis, suggesting the potential of KR-31543 for the treatment for atherosclerosis.

Association of CCR5, CCR2 and SDF1 gene polymorphisms with HIV-1 infection in Chinese population: a meta-analysis / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the association of CCR5δ32, CCR2-64I and SDFl-3 A gene polymorphisms with HIV-1-infection in Chinese population.</p><p><b>METHODS</b>A meta-analysis was performed to identify case-control studies of CCR5δ32, CCR2-64I and SDFl-3 A polymorphisms from the literatures.</p><p><b>RESULTS</b>Fourteen studies of CCR5δ32 were found, involving a total of 1607 cases and 1632 controls. Compared with the wild-type homozygote wt/wt, the pooled odds ratios (95%CI) of wt/mt, mt/mt, and wt/mt+mt/mt genotypes of CCR5δ32 gene polymorphisms were 1.156 (0.808, 1.654), 0.997 (0.198, 5.022), and 1.149 (0.808, 1.634), respectively. Twelve studies of CCR2-64I were identified, including 1415 cases and 1239 controls. Compared with the wild-type homozygote wt/wt, the pooled odds ratios (95%CI) of wt/mt, mt/mt, and wt/mt+mt/mt genotypes of CCR2-64I gene polymorphisms were 1.005 (0.844, 1.197), 1.191 (0.808, 1.754), and 1.028 (0.870, 1.214), respectively. Ten studies of SDFl-3 A were found, involving 1179 cases and 1003 controls. Compared with the wild-type homozygote wt/wt, the pooled odds ratios (95%CI) of wt/mt, mt/mt, and wt/mt + mt/mt genotypes of SDF1-3 A gene polymorphisms were 1.010 (0.830, 1.228), 1.188 (0.860, 1.643), and 1.038 (0.861, 1.250).</p><p><b>CONCLUSION</b>CCR5δ32, CCR2-64I and SDFl-3 A gene polymorphisms do not show strong correlations to HIV-1-infection in Chinese population. These 3 genes may not have protective effect against HIV-1 infection in Chinese population, suggesting the susceptibility of Chinese population to the infection.</p>

Relationship between expression of chemokine receptor and curative effect of multiple myeloma / 中国实验血液学杂志

This study was purposed to explore the correlation of CXCR4, CCR1, CCR2 expression with curative effect of multiple myeloma (MM). Flow cytometry was used to detect the expressions of CXCR4, CCR1, CCR2 on cell surface of bone marrow from 48 newly diagnosed MM patients. These patients were divided into two groups: one group with expression of chemokine receptor (group I) and another group without expression of chemokine receptor (group II). The group I was consisted of 34 patients, but 3 out of them could not be continuously followed up. The group II was consisted of 14 patients. The MM patients of 2 groups were treated with chemotherapeutic drugs for 3 and 6 months, the curative efficacy of 2 groups were compared. The results showed that after treating for 3 and 6 months the effective rates of group I and group II were 80.6% (25/31) vs 50% (7/14) and 83.9% (26/31) vs 50% (7/14) respectively, which suggested that curative efficacy of group I was better than that of group II (p < 0.05). It is concluded that CXCR4, CCR1, CCR2 may be used as indexes for evaluating curative effect of MM patients.

CCR2, MCP-1, SDF-1α & DC-sign gene polymorphisms in HIV-1 infected patients with & without tuberculosis.

Background & objectives: Variability in the clinical outcome of persons exposed to and infected with HIV-1 and tuberculosis (TB) is determined by multiple factors including host genetic variations. The aim of the present study was to find out whether chemokine, chemokine receptor and DC-SIGN gene polymorphisms were associated with susceptibility or resistance to HIV and HIV-TB in south India. Methods: CCR2 V64I (G/A), monocyte chemoattractant protein-1 (MCP-1) -2518 A/G, stromal cell derived factor-1α (SDF-1α) 3’UTR G/A and DC-SIGN gene polymorphisms were studied by polymerase chain reaction based methods in HIV-1 infected patients without TB (n=151), with pulmonary TB (PTB) (n=81) and extrapulmonary TB (n=31), 155 PTB patients without HIV and 206 healthy controls. Results: The genotype frequencies of CCR2 V64I, MCP-1 -2518 and DC-SIGN polymorphisms did not differ significantly between the study groups. A significantly increased frequency of GG genotype of SDF-1α polymorphism was observed among HIV+PTB+ patients compared to healthy controls (P=0.009, Pc=0.027). Interpretation & conclusions: Our data suggest that GG genotype of SDF-1α 3’UTR polymorphism may be associated with susceptibility to PTB in HIV-1 infected patients. A better understanding of genetic factors that are associated with TB could help target preventive strategies to those HIV patients likely to develop tuberculosis.

Change of serum MCP-1 level and CCR2 protein expression in isolated monocytes in patients with acute coronary syndrome / 中南大学学报(医学版)

OBJECTIVE@#To investigate the change of serum MCP-1 level and CCR2 expression in isolated monocytes in patients with acute coronary syndrome (ACS) and its possible relationship with ACS pathogenesis.@*METHODS@#Thirty ACS patients and 30 healthy controls were enrolled. Serum MCP-1 levels were determined by ELISA in all subjects. The protein expression of CCR2 in isolated monocytes was assessed by flow cytometry.@*RESULTS@#Serum MCP-1 concentrations in ACS patients were higher than those in healthy controls (P<0.05) and the ratio of CCR2 protein expression in monocytes in ACS patients was higher than that in healthy controls (P<0.01).@*CONCLUSION@#The serum MCP-1 concentrations and protein expression of CCR2 in ACS patients are significantly higher than those in healthy controls, which might be associated with the pathogenesis of ACS.

Association and preferential transmission of the CCR2V64I polymorphism with absence of asthma in high-risk families

To explore a possible association between the major functional CCR2V64I polymorphism and asthma and related phenotypes independent of atopy. We conducted this study in the Royal Aberdeen Children's Hospital, University of Aberdeen Medical School, United Kingdom from September 2004 to December 2006. One hundred and fifty-four unrelated nuclear families [598 individuals including children and parents] were identified from the local Grampian population. The major functional polymorphism CCR2V64I was analyzed for associations with asthma, lung function [forced expiratory volume% [FEV1%] of predicted], bronchial hyperresponsiveness [BHR] to methacholine, total serum-immunoglobulin E [s-IgE] and allergic sensitization [positive skin prick test to common allergens] in 154 asthmatic families. Pedigree disequilibrium test and case control analyses showed that the CCR2V64I polymorphism was significantly associated with the absence of asthma FEV1%, predicted above the population median of 83%, but not with s-IgE levels or specific sensitization. We identified associations between the V-64I CCR2 polymorphism and protection against asthma, higher FEV1, and absence of BHR in families at high risk of asthma and atopy, suggesting an important role for the CCR2 receptor in modulating airway inflammation independent of atopy