OBJECTIVETo 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.

METHODSThe 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.

RESULTSNo 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).

CONCLUSIONSThere 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.

Child ; Child, Preschool ; Female ; Genotype ; Humans ; Lymphohistiocytosis, Hemophagocytic ; genetics ; Male ; Polymorphism, Single Nucleotide ; Receptors, CCR2 ; genetics

BACKGROUND AND OBJECTIVES: A biallelic A/G polymorphism in the Monocyte chemotactic protein (MCP) -1 at position -2518 has been found to affect the level of MCP-1 expression. To investigate if these polymorphisms in chemokine ligand and receptor genes are relevant for the development of allergic rhinitis, we investigated polymorphisms of MCP-1 and CC chemokine receptor 2 (CCR2) known as the receptor of MCP-1. MATERIALS AND METHOD: Blood samples for genetic analysis were obtained from 198 individuals with allergic rhinitis and from 278 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for MCP-1 -2518 A/G (A/G polymorphism in the MCP-1 at position -2518) and CCR2 V64I polymorphisms (replacement of valine by isoleucine in CCR2 64) was used for genotyping. RESULTS: There were no differences in the frequencies of the genotypes in the controls and patients (p>0.05). The frequencies of the MCP-1 G and CCR2 A alleles were not statistically different between controls and allergic rhinitis patients (p>0.05). The odds ratios (95% confidence interval) of MCP-1 G/G and CCR2 A/A genotypes for allergic rhinitis were not statistically significant, whereas, alleles frequencies of MCP-1 -2518G and CCR2 A of controls were various according to the ethnic background. CONCLUSION: Our result suggests MCP-1 -2518 A/G and CCR2 V64I polymorphisms are not part of the factors contributing to genetical susceptibility in the development of allergic rhinitis in Koreans.
Alleles ; Genetic Predisposition to Disease* ; Genotype ; Humans ; Isoleucine ; Korea ; Monocytes ; Odds Ratio ; Receptors, CCR2 ; Rhinitis* ; Valine

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.
Chemokine CCL2/metabolism* ; Coronary Artery Disease/pathology* ; Death, Sudden, Cardiac/pathology* ; Humans ; Immunohistochemistry ; Receptors, CCR2/metabolism*

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.
Adult ; Aged ; Aged, 80 and over ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; metabolism ; Receptors, CCR1 ; metabolism ; Receptors, CCR2 ; metabolism ; Receptors, CXCR4 ; metabolism ; Treatment Outcome

OBJECTIVETo explore the association of CCR5δ32, CCR2-64I and SDFl-3 A gene polymorphisms with HIV-1-infection in Chinese population.

METHODSA meta-analysis was performed to identify case-control studies of CCR5δ32, CCR2-64I and SDFl-3 A polymorphisms from the literatures.

RESULTSFourteen 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).

CONCLUSIONCCR5δ32, 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.

Alleles ; Asian Continental Ancestry Group ; genetics ; Chemokine CXCL12 ; genetics ; Gene Frequency ; Genotype ; HIV Infections ; genetics ; HIV-1 ; Humans ; Polymorphism, Genetic ; Receptors, CCR2 ; genetics ; Receptors, CCR5 ; genetics

PURPOSE: This study was undertaken to elucidate whether CC chemokine receptor 2 (CCR2) exists in human peritoneal mesothelial cells (HPMCs) and whether monocyte chemoattractant protein-1 (MCP-1) has direct effects on epithelial to mesenchymal transition (EMT) and fibronectin expression in HPMCs. METHODS: HPMCs were isolated from a piece of human omentum and were incubated with M199 media containing 5.6 mM glucose (LG), 5.6 mM glucose+94.4 mM mannitol (LG+M), LG+10 ng/mL recombinant human MCP-1 (LG+MCP-1), or 100 mM glucose (HG) with or without a specific inhibitor of CCR2, 1.0 micrometer RS102895, for 4 days. Levels of secreted MCP-1 in culture media were determined by ELISA. Western blot was performed to determine fibronectin, E-cadherin, alpha-smooth muscle actin (alpha-SMA) and CCR2 protein expression. RESULTS: MCP-1 protein levels were significantly increased in HG-conditioned media compared to LG media (p<0.05). CCR2 protein was expressed in HPMCs, but there was no difference between LGand HG-stimulated cells. alpha-SMA protein expressions in HG and LG+MCP-1 groups were significantly higher relative to LG cells, while E-cadherin protein expressions were decreased in HG and LG+ MCP-1 groups compared to LG cells (p<0.05). In addition, there were significant increases in fibronectin mRNA and protein expression in HG and LG+MCP-1 groups (p<0.05). These HG-induced changes were significantly abrogated upon pre-treatment with RS102895. CONCLUSION: HG and MCP-1 directly induce EMT and enhance fibronectin expression in HPMCs, and these HG-induced changes were attenuated by the inhibition of MCP-1/CCR2 system, suggesting that increased MCP-1 levels by HG may contribute to the development of peritoneal fibrosis.
Actins ; Blotting, Western ; Cadherins ; Chemokine CCL2 ; Culture Media ; Enzyme-Linked Immunosorbent Assay ; Epithelial-Mesenchymal Transition ; Fibronectins ; Glucose ; Humans ; Mannitol ; Monocytes ; Muscles ; Omentum ; Peritoneum ; Receptors, CCR2 ; RNA, Messenger

OBJECTIVETo 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.

METHODSWild-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.

RESULTSCompared 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).

CONCLUSIONSCCR2 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.

Animals ; Hypertension ; complications ; pathology ; Kidney Diseases ; etiology ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, CCR2 ; antagonists & inhibitors ; physiology ; Sodium Chloride ; adverse effects ; TRPV Cation Channels ; physiology

OBJECTIVETo test the hypothesis that the CCL2/CCR2 signaling pathway plays an important role in pain induced by experimental tooth movement.

METHODSMale 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.

RESULTSExperimental 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.

CONCLUSIONSThe 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.

Animals ; Chemokine CCL2 ; physiology ; Immunohistochemistry ; Male ; Neurons ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR2 ; physiology ; Signal Transduction ; Tooth Movement Techniques ; adverse effects ; Toothache ; etiology ; Trigeminal Ganglion ; Up-Regulation

OBJECTIVETo determine the role of chemokine receptor 2 (CCR2) in the development of salt-sensitive hypertension-induced renal damage.

METHODSWe 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.

RESULTSDOCA-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).

CONCLUSIONBlockade 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.

Animals ; Disease Models, Animal ; Hypertension ; chemically induced ; physiopathology ; Kidney ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, CCR2 ; metabolism ; Sodium Chloride, Dietary ; toxicity

Alcoholism ; metabolism ; Animals ; Brain ; metabolism ; Chemokine CCL2 ; genetics ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR2 ; genetics ; metabolism