This study was aimed to explore the expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 in bcr/abl fusion gene positive CML cells, and to study the effects of P210(bcr/abl) fusion protein tyrosine kinase on expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNAs in chronic myeloid leukemia cells. The expression levels of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNA were detected by semi-quantitative RT-PCR in bcr/abl negative cells, bcr/abl positive cells, and P210(bcr/abl)-Rb-C-Box positive cells. The results showed that MIP-1alpha and CCR-1 mRNAs were expressed in bcr/abl negative cells, but not in positive cells. Both MCP-1 and CCR-2 mRNA cannot be detected in both bcr/abl positive and negative cells. After inhibiting P210(bcr/abl) tyrosine kinase activity by Rb-C-Box, expressions of MIP-1alpha and CCR-1 mRNAs were restored to normal (similar to P210(bcr/abl) negative cells). It is concluded that P210(bcr/abl) fusion protein inhibits the expression of MIP-1alpha and CCR-1 in chronic myeloid leukemia cells, but does not inhibit MCP-1 and CCR-2 mRNA expressions in these leukemia cells.
Chemokine CCL2 ; biosynthesis ; genetics ; Chemokine CCL3 ; Chemokine CCL4 ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; Macrophage Inflammatory Proteins ; biosynthesis ; genetics ; Receptors, CCR1 ; Receptors, CCR2 ; Receptors, Chemokine ; biosynthesis ; genetics ; Tumor Cells, Cultured

Objective: To assess the association of genetic polymorphisms and circulating levels of chemokine monocyte chemoattractant protein-1 (MCP1) with risk of breast cancer. Methods: A total of 820 patients with pathologically confirmed breast cancer and 900 age-and area-of-residence-matched healthy controls who visited the hospital for routine health screening during the same period were included in this case-control study. Mendelian randomization analysis was performed using three widely followed functional single nucleotide polymorphisms (SNPs) of the MCP1 gene rs1024611, rs2857656 and rs4586 to construct instrumental variables . Results: MCP1 rs1024611 (OR=1.26, P=0.002), rs2857656 (OR=1.23, P=0.006) and rs4586 (OR=1.23, P=0.003) were significantly associated with increased risk of breast cancer. SNP rs1024611 (β=1.194, P<0.001), rs2857656 (β=1.221, P<0.001) and rs4586 (β=1.137, P<0.001) were positively correlated with higher circulating level of MCP1. The case-control study showed that an increase of 23.7 pg/ml of circulating levels of MCP1 was associated with a 0.25-fold increased risk of breast cancer. MR analysis confirmed that the genetic predicted circulating levels of MCP1 were associated with an increased risk of breast cancer, and the risk of breast cancer increased by 0.20 times with an increase of 23.7 pg/ml in MCP1. Conclusion: Genetic variants and circulating levels of MCP1 are significantly associated with the risk of breast cancer and can be used as a biomarker for early prediction of breast cancer.
Breast Neoplasms/genetics* ; Case-Control Studies ; Chemokine CCL2/genetics* ; Female ; Humans ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide

OBJECTIVE: To explore the microvessel counts and the expressions of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 ( MIP-1) alpha mRNA in the pathological scar tissues. METHODS: Immunohistochemical method of avidin-biotin complex was used for microvessel counts on the routinely formalin-fixed and paraffin-embedded sections of specimens of hypertrophic scars, keloids, normal skin, and surgical scar, and in situ hybridization for the expressions of IL-8, MCP-1, MIP-1alpha mRNA. RESULTS: The microvessel counts as well as the positive rates and the scorings of IL-8, MCP-1, and MIP-1alpha mRNA were significantly higher in pathological scars than those in the normal skin and surgical scar (all P < 0.05). The microvessel counts were significantly higher in the positive cases of IL-8, MCP-1 and MIP-1alpha mRNA than those in the negative ones (P < 0.05). The close positive correlations were found among the microvessel counts and the expressive scorings of 3 factors (P < 0.05). The close positive correlations were also found among the expressive scorings of IL-8, MCP-1, and MIP-1alpha mRNA in pathological scars. Microvessel counts were significantly higher in hypertrophic scars with the course less than 1 year than those with the course more than 1 year. CONCLUSION IL-8, MCP-1 and MIP-1alpha play important roles in promoting the neovascularization of pathological scars.
Adolescent ; Adult ; Burns ; complications ; Capillaries ; metabolism ; Chemokine CCL2 ; biosynthesis ; genetics ; Chemokine CCL3 ; Chemokine CCL4 ; Cicatrix ; etiology ; metabolism ; Female ; Humans ; Interleukin-8 ; biosynthesis ; genetics ; Macrophage Inflammatory Proteins ; biosynthesis ; genetics ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Skin ; blood supply

OBJECTIVETo investigate the association between single nucleotide polymorphisms (SNP) of angiopoietin-2 (Ang-2) gene and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN).

METHODSGenotype and allele frequency of Ang-2 were detected by amplification refractory mutation system-PCR(ARMS-PCR) in 221 cases with T2DM and 104 normal controls. Monocyte chemoattractant protein-1(MCP-1) was measured by ELISA. DN patients were divided into three groups according to urinary albumin excretion rates (UAER), i.e. DN0: UAER < 30 mg/24 h, DN1: UAER 30-300 mg/24 h and DN2: UAER > 300 mg/24 h.

RESULTSStatistics showed: (1) Genotype frequencies and allele frequencies in Ang-2 1233A/G had significant difference but not Ang-2 759T/G and 1078A/G; (2) Comparing with those with genotype AA, the relative risk of genotype (AG+ GG) suffered from T2DM and DN were 2.265 fold (OR= 2.265, 95% CI: 1.223-1.402, P= 0.031), 1.789 fold (OR= 1.789, 95% CI: 0.889-1.021, P= 0.012), respectively; (3) The onset of DN was related to Ang-2 1233A/G allele G (r= 1.321, OR= 1.427, 95% CI: 2.324-4.177, P= 0.034).

CONCLUSIONAng-2 1233A/G polymorphism may be associated with T2DM and involved in onset and development of DN.

Angiopoietin-2 ; genetics ; Case-Control Studies ; Chemokine CCL2 ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Diabetic Nephropathies ; genetics ; Gene Frequency ; Genotype ; Humans ; Polymorphism, Single Nucleotide

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

OBJECTIVEKawasaki disease (KD) is a febrile illness of childhood. The etiology of KD remains unknown. Multiple theories exist, including an infectious etiology and an immunological abnormality. Cardiac involvement ranges from myocarditis and pericarditis in the acute stage to the development of coronary artery aneurysms later in the course. The present study aimed to explore the effect of monocyte chemotactic protein-1 (MCP-1) in Kawasaki disease and its relationship with damage to the coronary arteries during the development of KD.

METHODSPlasma MCP-1 concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and MCP-1 mRNA expression in peripheral blood mononuclear cells (PBMC) was measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in comparison of three groups: 56 patients with KD, 60 age-matched patients with non-infectious diseases, and 66 age-matched febrile patients with various diseases.

RESULTSPlasma MCP-1 concentration and MCP-1 mRNA expression in PBMC of patients with active KD [(409.55 +/- 97.42) pg/ml] and (1.97 +/- 0.77) were higher than those of control group. Plasma MCP-1 levels and MCP-1 mRNA expression of inactive KD group [(301.64 +/- 71.55) pg/ml] and (1.31 +/- 0.39) were significantly higher than those of non-infectious diseases patients. There was a marked increase in patients with inactive KD than those of non-infective patients, but there were no significant differences between inactive KD and febrile patients. Plasma MCP-1 levels and MCP-1 mRNA expression were markedly increased in KD patients with coronary artery lesions than those in patients without coronary artery lesions.

CONCLUSIONPlasma MCP-1 concentration and MCP-1 mRNA expression in PBMC were significantly increased in patients with KD, and they were higher in KD with coronary artery lesions. It indicates that MCP-1 may be a useful parameter for monitoring disease activity in patients with KD.

Chemokine CCL2 ; blood ; genetics ; metabolism ; Child ; Child, Preschool ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Leukocytes, Mononuclear ; metabolism ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; genetics ; pathology ; RNA, Messenger ; genetics

Cells, Cultured ; Chemokine CCL2 ; biosynthesis ; genetics ; Endothelial Cells ; metabolism ; Humans ; Mitogen-Activated Protein Kinases ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; Umbilical Veins ; cytology ; p38 Mitogen-Activated Protein Kinases

OBJECTIVETo determine the role of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 (HMGB-1) in the pathogenesis of lupus nephritis.

METHODSSerum levels of anti-dsDNA antibodies were determined by enzyme linked immunosorbent assay (ELISA). Renal morphologic features were examined by light microscopy, electron microscopy, and immunohistologic analyses. The mRNA expression of HMGB-1 and monocyte chemoattractant protein-1 (MCP-1) was detected by RT-PCR.

RESULTMRL/lpr mice demonstrated characteristic alterations of serum immune parameters, with progressively increased anti-dsDNA antibodies with age, compared with age-matched C57BL/6J mice. MRL/lpr mice showed progressive development of renal damage, starting at 12 weeks of age and reached the peak at 20 weeks. The observed lesions included the presence of enlarged hypercellular glomeruli, with increased numbers of both resident cells and infiltrating leukocytes. Higher expression of HMGB-1 mRNA was found in MRL/lpr mice than what in C57BL/6J mice. Expression of HMGB-1 was positively correlated with that of MCP-1 mRNA.

CONCLUSIONThe results demonstrate that the higher expression of HMGB-1 may contribute to the pathogenesis of lupus nephritis.

Animals ; Chemokine CCL2 ; metabolism ; Disease Models, Animal ; HMGB1 Protein ; genetics ; metabolism ; Kidney ; metabolism ; pathology ; Lupus Nephritis ; metabolism ; pathology ; Mice ; Mice, Inbred MRL lpr ; RNA, Messenger ; genetics

OBJECTIVETo investigate the effects of very low-density lipoprotein (VLDL) on cellular lipid accumulation and the expression of monocyte chemoattractant protein-1 (MCP-1) in human mesangial cells.

METHODSAn established stable human mesangial cell line (HMCL) was used in all experiments. VLDL-induced cellular lipid deposition was visualized by Oil Red O staining and analyzed quantitatively by standard enzymatic procedures. MCP-1 mRNA and protein expression levels in treated HMCLs were determined by real-time quantitative RT-PCR and enzyme-linked immunosorbent assay, respectively. For adhesion study, HMCLs were treated with VLDL for 12 hours, followed by a one-hour incubation with THP-1 cells.

RESULTSVLDL induced cellular lipid accumulation in HMCLs in a time- (0-24 h) and dose- (0-200 microg/ml) dependent manner, and the principal component of accumulated lipid is triglyceride. In HMCLs, MCP-1 mRNA expression was promoted by VLDL in a time- (0-6 h) and dose- (0-100 microg/ml) dependent manner, and VLDL also enhanced MCP-1 secretion in a dose-dependent manner. Such an effect was accompanied by increased adhesion of monocytes to HMCLs.

CONCLUSIONSVLDL can induce cellular triglyceride accumulation and upregulate the expression of MCP-1 in human mesangial cells. Hence, VLDL may be involved in the pathogenesis of lipid-mediated renal injury.

Cell Line ; Chemokine CCL2 ; genetics ; metabolism ; Humans ; Lipoproteins, VLDL ; pharmacology ; toxicity ; Mesangial Cells ; cytology ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Triglycerides ; metabolism

OBJECTIVETo evaluate the possibility and efficiency of nanoparticle as a new vector in specific gene transference.

METHODSNanoparticle-DNA complex was prepared with Poly-dl-lactic-co-glycolic acid (PLGA) bearing anti-sense monocyte chemotactic protein-1 (A-MCP-1), 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 microg), 6 with A-MCP-1 (200 microg) by cationic liposome, 4 with LNCX plasmid, and 4 as control. Fourteen days after the grafts were harvested, the expression of A-MCP-1 and its effect on MCP-1 in vein grafts were detected by dot blot, and the morphologic evaluation of grafts was performed.

RESULTSThe package efficiency of the nanoparticle-DNA complex was 0.9%, release progress in vitro lasted 2 weeks, and the size ranged from 150 to 300 nm. SMC genomic DNA PCR showed that A-MCP-1 gene could be successfully transfected into cells by nanoparticle. The study in vivo indicated that A-MCP-1 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.

CONCLUSIONNanoparticle can act as a vector to transfect specific gene.

Animals ; Chemokine CCL2 ; biosynthesis ; genetics ; DNA, Antisense ; biosynthesis ; genetics ; Drug Carriers ; Gene Expression ; Genetic Therapy ; Genetic Vectors ; Lactic Acid ; Nanotechnology ; Particle Size ; Polyglycolic Acid ; Polymers ; Rabbits ; Transfection