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 culture osteoblast in vitro and evaluate CCL3 receptor CCR1 expression in patients with multiple myeloma (MM).

METHODSBone marrow osteoblasts from MM patients were cultured in vitro with dexamethasone, β-sodium glycerophosphate and vitamin C, which were identified by alkaline phosphatase staining, Von Kossa's staining. The CCL3 receptor expression was evaluated by flow cytometry. The morphology and quantity of osteoblast were observed after exposure to CCL3.

RESULTSBone marrow osteoblasts from MM patients could be cultured in vitro and be identified by positive staining of alkaline phosphatase and Von Kossa's. MM-derived osteoblasts expressed higher levels of CCR1 (74.48 ± 7.31)%, compared with normal controls (48.35 ± 8.81)%. Calcium deposition of osteoblasts after exposure to CCL3 was less than that of controls.

CONCLUSIONBone marrow osteoblasts could be cultured in vitro from MM Patients. CCL3 may contribute to the development of myeloma bone disease.

Adult ; Aged ; Cells, Cultured ; Chemokine CCL3 ; pharmacology ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; pathology ; Osteoblasts ; cytology ; drug effects ; metabolism ; Receptors, CCR1 ; metabolism ; Young Adult

UNLABELLEDBACKGROWND: Macrophage inflammatory protein-1α (MIP-l α/CCL3) belongs to the C-C chemokine family (CCL3), which can be secreted by macrophages, other types of hematopoietic cells and bone marrow stromal cells. Higher levels of MIP-1α were found to be associated with several kinds of hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML). Moreover, MIP-1α has been reported to be an adverse prognostic factor for CLL. However, the impact of MIP-1α on acute myeloid leukemia (AML) has been poorly investigated.

OBJECTIVETo investigate the influence of MIP-1α on proliferction of AML cells.

METHODSUsing MLL-AF9 induced AML mouse model, the expression of MIP-1α was measured by real time quantitative RT-PCR. AML cell proliferation was examined by cell counting and colony forming assay (CFC). The influence of blocking the MIP-1α action on the growth and pathogenic ability of AML cells was explored by using the small molecule antagonist for interfering interaction of MIP-1α with its receptor CCR1.

RESULTSThe MIP-1α could promote the proliferation and colony formation of AML cells, the blocking MIP-1a could inhibit the growth of AML cells and delay onset of AML.

CONCLUSIONThe MIP-1a promotes the occurence and progression of AML, therefore blocking the MIP-1α signal pathway may be served as a strategy to inhibit the growth of AML cells, and MIP-1α can be a potential target for treatment of AML.

Animals ; Cell Line, Tumor ; Cell Proliferation ; Chemokine CCL3 ; Chemokine CCL4 ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Macrophage Inflammatory Proteins ; Mice ; Multiple Myeloma ; Receptors, CCR1

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

The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors (TCRs) or chimeric antigen receptors (CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma.
B-Lymphocytes ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Humans ; Immunotherapy, Adoptive ; Leukemia ; Lymphoma, B-Cell ; therapy ; Lymphoma, Non-Hodgkin ; therapy ; Neoplasms ; Receptors, Antigen ; Receptors, Antigen, T-Cell ; Receptors, CCR1 ; T-Cell Antigen Receptor Specificity ; T-Lymphocytes

BACKGROUNDChronic obstructive pulmonary disease (COPD) is a progressive disease associated with a cellular inflammatory response mostly concerned with cigarette smoking. Chemokine receptors CCR1/5 play an important role in the inflammatory cells recruitment in the lung of COPD patients. The aim of this study was to determine the impact of cigarette smoking on the expression of CCR1/5 on inflammatory cells in induced sputum, and the relationship between the receptors expression and COPD severity.

METHODSDifferential cells in induced sputum were counted and the optical densities of CCR1 and CCR5 on inflammatory cells in induced sputum from COPD patients (n = 29), healthy smokers (n = 11), and nonsmokers (n = 6) were measured using immunocytochemistry. Concentrations of CCL3, the ligand of CCR1/5, in supernatant of induced sputum were detected by enzyme-linked immunosorbent assay.

RESULTSThe expressions of CCR1 and CCR5 on inflammatory cells in healthy smokers were significantly higher than those in nonsmokers, and the expression of CCR1 in patients with COPD was significantly increased when compared with nonsmokers but not healthy smokers. The expressions of CCR1 and CCR5 on inflammatory cells in severe and very severe COPD patients were higher compared with mild and moderate COPD patients. CCL3 level was positively correlated with the total cell counts in induced sputum and smoking history, and negatively correlated with percentage of predicted FEV(1).

CONCLUSIONSCigarette smoking could increase the expression of CCR1 on the inflammatory cells. Both CCR1 and CCR5 expressions on the inflammatory cells in induced sputum could be associated with COPD severity.

Adult ; Aged ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; immunology ; metabolism ; Receptors, CCR1 ; metabolism ; Receptors, CCR5 ; metabolism ; Smoking ; adverse effects ; Sputum ; cytology ; immunology

BACKGROUND: Upregulation of one type of the pro-inflammatory chemokine (CCL2) and its receptor (CCR2) following peripheral nerve injury contributes to the induction of neuropathic pain. Here, we examined whether another type of chemokine (CCL3) is involved in neuropathic pain. METHODS: We measured changes in mechanical and thermal sensitivity in the hind paws of naive rats or rats with an L5 spinal nerve ligation (SNL) after intra-plantar injection of CCL3 or met-RANTES, an antagonist of the CCL3 receptor, CCR1. We also measured CCL3 levels in the sciatic nerve and the hind paw skin as well as CCR1 expression in dorsal root ganglion (DRG) cells from the lumbar spinal segments. RESULTS: Intra-plantar injection of CCL3 into the hind paw of naive rats mimicked L5 SNL-produced hyperalgesia. Intra-plantar injection of met-RANTES into the hind paw of rats with L5 SNL attenuated hyperalgesia. L5 SNL increased CCL3 levels in the sciatic nerve and the hind paw skin on the affected side. The number of CCR1-positive DRG cells in the lumbar segments was not changed following L5 SNL. CONCLUSIONS: Partial peripheral nerve injury increases local CCL3 levels along the degenerating axons during Wallerian degeneration. This CCL3 binds to its receptor, CCR1, located on adjacent uninjured afferents, presumably nociceptors, to induce hyperalgesia in the neuropathic pain state.
Animals ; Axons ; Chemokine CCL3 ; Chemokine CCL5 ; Diagnosis-Related Groups ; Ganglia, Spinal ; Hyperalgesia ; Ligation ; Neuralgia ; Nociceptors ; Peripheral Nerve Injuries ; Peripheral Nerves ; Rats ; Receptors, CCR1 ; Sciatic Nerve ; Skin ; Spinal Nerves ; Up-Regulation ; Wallerian Degeneration

Asthma is a chronic inflammatory respiratory disease accompanied with airway inflammation, airway remodeling and bronchial hyperresponsiveness. Chemokines are important for the recruitment of immune cells to the lung, which play an important role in the formation and development of asthma. Targeting the chemokine receptors to anti-inflammation and anti-asthma is a new strategy and some candidate drugs are discovered recently. This review is focused on the development of chemokine receptor antagonists for anti-asthma, which will promote the compound designations.
Animals ; Anti-Asthmatic Agents ; pharmacology ; therapeutic use ; Asthma ; drug therapy ; Heterocyclic Compounds ; pharmacology ; Humans ; Phenylurea Compounds ; therapeutic use ; Piperidines ; pharmacology ; therapeutic use ; Pyridazines ; pharmacology ; Receptors, CCR1 ; antagonists & inhibitors ; Receptors, CCR3 ; antagonists & inhibitors ; Receptors, CCR4 ; antagonists & inhibitors ; Receptors, CXCR4 ; antagonists & inhibitors ; Receptors, Chemokine ; antagonists & inhibitors

Chemokines and chemokine receptors play a role in migration of circulating leukocytes to the region of inflammation. Human LZIP is an uncharacterized transcription factor and is known to participate in leukotactin (Lkn)-1/CCL15-induced cell migration. We investigated the role of human LZIP in expression of CC chemokine receptors (CCRs) and its involvement in monocyte migration. RNase protection analysis showed that LZIP increased mRNA expression of CCR2 and CCR1 in THP-1 cells. Surface expressions of both CCR2 and CCR1 were also increased by LZIP. Results from an electrophoretic mobility shift assay showed that LZIP binds to the C/EBP element in the CCR2 promoter. LZIP also enhanced the chemotactic activities of monocyte chemoattractant protein-1/CCL2 and Lkn-1. These results suggest that LZIP regulates expression of chemokine receptors that are involved in monocyte migration.
Atherosclerosis/drug therapy/etiology ; CCAAT-Enhancer-Binding Proteins/genetics/immunology/*metabolism ; Cell Line, Tumor ; Cell Movement/drug effects/*physiology ; Chemokine CCL2/*pharmacology ; Chemokines, CC/pharmacology ; Cyclic AMP Response Element-Binding ; Humans ; Macrophage Inflammatory Proteins/pharmacology ; Monocytes/drug effects/metabolism ; Promoter Regions, Genetic ; Protein Binding ; RNA, Messenger/analysis ; Receptors, CCR1/biosynthesis/genetics ; Receptors, CCR2/*biosynthesis/genetics ; Transcriptional Activation/drug effects ; Transfection ; Transgenes

9-cis-retinoic acid (9CRA) plays an important role in the immune response; this includes cytokine production and cell migration. We have previously demonstrated that 9CRA increases expression of chemokine receptors CCR1 and CCR2 in human monocytes. To better understand how 9CRA induces CCR1 and CCR2 expression, we examined the contribution of signaling proteins in human monocytic THP-1 cells. The mRNA and surface protein up-regulation of CCR1 and CCR2 in 9CRA-stimulated cells were weakly blocked by the pretreatment of SB202190, a p38 MAPK inhibitor, and PD98059, an upstream ERK inhibitor. Activation of p38 MAPK and ERK1/2 was induced in both a time and dose-dependent manner after 9CRA stimulation. Both p38 MAPK and ERK1/2 phosphorylation peaked at 2 h after a 100 nM 9CRA treatment. 9CRA increased calcium influx and chemotactic activity in response to CCR1-dependent chemokines, Lkn-1/CCL15, MIP-1alpha/CCL3, and RANTES/CCL5, and the CCR2-specific chemokine, MCP-1/CCL2. Both SB202190 and PD98059 pretreatment diminished the increased calcium mobilization and chemotactic ability due to 9CRA. SB202190 inhibited the expression and functional activities of CCR1 and CCR2 more effectively than did PD98059. Therefore, our results demonstrate that 9CRA transduces the signal through p38 MAPK and ERK1/2 for CCR1 and CCR2 up-regulation, and may regulate the pro-inflammatory process through the p38 MAPK and ERK-dependent signaling pathways.
Calcium Signaling/drug effects ; Cell Line ; Chemokines/pharmacology ; Chemotaxis, Leukocyte/drug effects ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Flavonoids/pharmacology ; Gene Expression Regulation/*drug effects ; Humans ; Imidazoles/pharmacology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Monocytes/drug effects/*enzymology ; Pyridines/pharmacology ; RNA, Messenger/genetics/metabolism ; Receptors, CCR1 ; Receptors, CCR2 ; Receptors, Chemokine/*genetics/metabolism ; Tretinoin/*pharmacology ; p38 Mitogen-Activated Protein Kinases/*metabolism