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

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

OBJECTIVETo investigate the effect of folic acid on homocysteine (Hcy)-induced chemokine secretion and NADPH oxidase activity in human monocytes.

METHODSHuman monocytes from healthy volunteers were incubated with Hcy (100 micromol/L) with or without folic acid (5 micromol/L) for 24 h; MCP-1 and IL-8 were assessed by ELISA. DCFH-DA was added to monitor intracellular ROS production on confocal microscopy. A cytochrome c reduction assay was used to measure NADPH oxidase activity.

RESULTSThe Hcy-induced secretion of MCP-1 and IL-8 was significantly reduced by folic acid [(1.88 +/- 0.51) ng/ml vs. (4.36 +/- 0.72) ng/ml vs. (2.40 +/- 0.60) ng/ml and (4.9 +/- 1.9) ng/ml vs. (12.7 +/- 1.5) ng/ml vs. (7.2 +/- 1.9) ng/ml, all P < 0.05]. The Hcy-induced production of ROS was also significantly attenuated by folic acid. Moreover, the Hcy-induced NADPH oxidase activity increase was significantly inhibited by cotreatment with folic acid.

CONCLUSIONFolic acid may attenuate oxidative stress induced by Hcy by reducing NADPH oxidase activity in monocytes.

Cells, Cultured ; Chemokines ; secretion ; Folic Acid ; pharmacology ; Homocysteine ; pharmacology ; Humans ; Interleukin-8 ; metabolism ; Monocytes ; drug effects ; secretion ; NADPH Oxidases ; metabolism ; Oxidative Stress ; drug effects ; Receptors, CCR2 ; metabolism

OBJECTIVETo 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.

METHODSTHP-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.

RESULTSThe 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).

CONCLUSIONSPg-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.

Cell Line ; Dose-Response Relationship, Drug ; Humans ; Lipopolysaccharides ; pharmacology ; Monocytes ; cytology ; metabolism ; Porphyromonas gingivalis ; chemistry ; RNA, Messenger ; metabolism ; Receptors, CCR2 ; genetics ; metabolism ; Time Factors ; 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

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.
Artemisia ; chemistry ; Asteraceae ; chemistry ; Drug Evaluation, Preclinical ; Humans ; Kinetics ; Plant Extracts ; chemistry ; pharmacology ; Receptors, CCR2 ; antagonists & inhibitors ; genetics ; metabolism ; Structure-Activity Relationship

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.
Acute Coronary Syndrome ; blood ; Adult ; Case-Control Studies ; Chemokine CCL2 ; blood ; Female ; Humans ; Male ; Middle Aged ; Monocytes ; metabolism ; Receptors, CCR2 ; blood

Ascites ; metabolism ; Carcinoma, Hepatocellular ; blood ; metabolism ; pathology ; Chemokine CCL2 ; blood ; metabolism ; Hepatitis B, Chronic ; blood ; metabolism ; Humans ; Immunohistochemistry ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; blood ; metabolism ; pathology ; Liver Neoplasms ; blood ; metabolism ; pathology ; Receptors, CCR2 ; blood ; metabolism

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.
Animals ; Brain Injuries/pathology* ; Cerebral Cortex/physiopathology* ; Chemokine CCL2/metabolism* ; Chemokines, CC/metabolism* ; Hypoxia-Ischemia, Brain/metabolism* ; Macrophage Inflammatory Proteins/metabolism* ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; Receptors, CCR2/metabolism*