Human immunodeficiency virus type 1 (HIV-1) requires both CD4 and a coreceptor to infect cells. Macrophage-tropic (M-tropic) HIV-1 strains utilize the chemokine receptor CCR5 in conjunction with CD4 to infect cells, while T-cell-tropic (T-tropic) strains generally utilize CXCR4 as a coreceptor. Some viruses can use both CCR5 and CXCR4 for virus entry (i.e., are dual-tropic), while other chemokine receptors can be used by a subset of virus strains. Due to the genetic diversity of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) and the potential for chemokine receptors other than CCR5 or CXCR4 to influence viral pathogenesis, we tested a panel of 28 HIV-1, HIV-2, and SIV envelope (Env) proteins for the ability to utilize chemokine receptors, orphan receptors, and herpesvirus-encoded chemokine receptor homologs by membrane fusion and virus infection assays. While all Env proteins used either CCR5 or CXCR4 or both, several also used CCR3. Use of CCR3 was strongly dependent on its surface ...

US28 is a constitutively active chemokine receptor encoded by CMV (also referred to as human herpesvirus 5), a highly prevalent human virus that infects a broad spectrum of cells, including intestinal epithelial cells (IECs). To study the role of US28 in vivo, we created transgenic mice (VS28 mice) in which US28 expression was targeted to IECs. Expression of US28 was detected in all IECs of the small and large intestine, including in cells expressing leucine rich repeat containing GPCR5 (Lgr5), a marker gene of intestinal epithelial stem cells. US28 expression in IECs inhibited glycogen synthase 3β (GSK-3β) function, promoted accumulation of β-catenin protein, and increased expression of Wnt target genes involved in the control of the cell proliferation. VS28 mice showed a hyperplastic intestinal epithelium and, strikingly, developed adenomas and adenocarcinomas by 40 weeks of age. When exposed to an inflammation-driven tumor model (azoxymethane/dextran sodium sulfate), VS28 mice developed a

Our data demonstrate that the ability of DCs to activate T cells and to efficiently induce their expansion does not predict their ability to induce CTL activity and the ability to respond to peripheral-type chemokines. In contrast, we observed that although the expansion of CD8+ T cells can be driven efficiently by the DCs matured in a wide spectrum of inflammatory conditions, the induction of the CD8+ T cell effector functions in naive CD8+ T cells and a switch in their chemokine responsiveness was a sole property of the nonexhausted IL-12-producing DCs matured in the conditions that mimic acute inflammation (presence of IFNs and TLR ligands). This inflammatory pathway of activation of CD8+ T cells, associated with the IL-12-dependent induction of GrBhigh CTLs, eventually results in a resting population of memory-type (CD8+CD45RO+GrBlow) cells. In accordance with the previously reported long-lived character of cells activated by the high IL-12-producing DC1s (14) and with the ability of ...

The protein encoded by this gene is a receptor for C-C type chemokines. It belongs to family 1 of the G protein-coupled receptors. This receptor binds and responds to a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5). It is highly expressed in eosinophils and basophils, and is also detected in TH1 and TH2 cells, as well as in airway epithelial cells. This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway. It is also known to be an entry co-receptor for HIV-1. This gene and seven other chemokine receptor genes form a chemokine receptor gene cluster on the chromosomal region 3p21. Alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2009 ...

We generated Th1 and Th2 lines by stimulating human cord blood lymphocytes with mitogen in the presence of IL-12 and neutralizing anti-IL-4 mAb or IL-4 and neutralizing anti-IL-12 mAb, respectively. As previously reported, this protocol allows the establishment of human T cell lines with strongly polarized cytokine production (8). As shown at the single cell level by measuring intracellular cytokine production (Fig. 1), neonatal T cells primed under the Th1 conditions differentiated into T cells producing IFN-γ but little IL-4, whereas naive T cells primed in the presence of IL-4 and anti-IL-12 resulted in a population of T cells producing mainly IL-4. To assess the selective expression of chemokine receptors in the different T cell subsets, we have analyzed the messenger RNA (mRNA) expression levels for the different chemokine receptors in both Th1 and Th2 lines, as well as in naive cells. As shown in Fig. 2, polarized Th1s and Th2s showed differential expression of chemokine receptors. Naive ...

In this report, we provide the first evidence that blood-borne human CD4+CD25+ Treg cells exhibit a distinctive chemotactic response profile and chemokine receptor expression. Treg cells exhibit chemotactic responsiveness to several inflammatory and lymphoid chemokines, but they are specifically hyperresponsive to chemokines that engage the chemokine receptors CCR4 and CCR8 (Fig. 1).. Our investigation documents a broad spectrum of responsiveness of Treg cells to inflammatory chemokines that could potentially allow access to inflamed tissues and contact responding T cells and APCs. However, the specificity of action of chemokines such as CCL17, CCL22, and CCL1 on Treg cells suggests a unique role for these chemokines and their receptors in the physiology of Treg cells. Activated T cells and professional APCs such as DCs and monocytes/macrophages can produce CCL1, CCL17, and CCL22 (15)(16)(18). CCL17 and CCL22 secreted by activated DCs have been shown to attract activated T cells expressing CCR4 ...

Microglia are the cells primarily responsible for viral load in the CNS, where they probably play a role in the development of HIVD, and because of poor penetration of antiretrovirals into the CNS, they may serve as a potential sanctuary site for the virus (4). Since virus replication can differ between microglia and MDM (44), understanding the virus-cell biology in microglia is critical for the development of strategies to treat HIVD. The discovery that chemokine receptors act as HIV coreceptors has been a major advance in delineating tropism, and the role of these receptors in microglial entry and replication has been the subject of recent publications (16, 19, 43). Here we have shown that three major chemokine receptors implicated in HIV entry, CCR5, CCR3, and CXCR4, are expressed on adult microglial cells, albeit at different levels (Fig. 2). Two of these, CCR5 and CXCR4, are functional chemokine receptors, as measured by their abilities to mediate signal transduction after stimulation ...

At entry, the patients with RA showed impaired cytokine secretion of PBMC in response to PHA stimulation in comparison with controls, suggesting decreased peripheral T cell function as reported earlier.16-18 The TNFα blockade normalised the mitogen response of PBMC as shown by the normal production of both IFNγ and IL4. Activation of type 1 immune response, described as an increase in the number of PBMC spontaneously producing IFNγ after 4 weeks of treatment with etanercept, a soluble TNF receptor, has been reported earlier by Berg et al.11 Also IFNγ production of PBMC stimulated with microbial antigens (purified protein derivative, influenza virus) or autoantigen (collagen type II) increased in the patients during treatment. No increase in the mitogen stimulated IFNγ production was found, but instead, an increase in the secretion of IL2 was seen. Increased secretion of IL2 and IFNγ has also been reported in patients with spondyloarthropathy receiving infliximab.19 As a conclusion, these ...

TY - JOUR. T1 - Use of shRNA for stable suppression of chemokine receptor expression and function in human cancer cell lines. AU - Salazar, Nicole. AU - Muñoz, Daniel. AU - Hoy, James. AU - Lokeshwar, Bal L.. PY - 2014. Y1 - 2014. N2 - In this chapter, we describe a protocol used for stable silencing of chemokine receptor CXCR7 in human cancer cells using shRNA in a lipid transfection setting, previously published by our laboratory. We provide thorough detail and background information about the process of shRNA to clarify the importance of this process. We use CXCR7 shRNA and scrambled sequence shRNA constructs cloned into a pRS plasmid under the control of a U6 promoter for stable expression. Human cancer cells are transfected with shRNA-pRS using Lipofectamine 2000. Cells stably expressing the shRNA are selected from transfected cultures following 2 weeks in medium containing the selection antibiotic puromycin. The emergent cell colonies are evaluated for knockdown of CXCR7 mRNA and protein ...

Cells were first stained with anti- CD16/32 (2.4G2) for 10 minutes at 4C, then with ETP-46321 specifically conjugated antibodies for 30 minutes at 4C in the dark. to anti-PD-1, and their induction in non- responsive murine tumors promoted responsiveness to anti-PD-1. Our data suggest that the CXCR3 chemokine system is usually a biomarker for sensitivity to PD-1 blockade and that augmenting the intratumoral function of EMR2 this chemokine system could improve clinical outcomes. eTOC Blurb Chow et al. find the CXCR3 chemokine system is not required for CD8+ T cell migration into the tumor, but rather for the enhancement of the intratumoral CD8+ T cell response in the context of PD-1 blockade. The CXCR3 chemokine system may serve as a biomarker for sensitivity to PD- 1 blockade and a target for improving clinical outcomes. Introduction CD8+ T cells play a vital role in tumor eradication through the production of cytotoxic molecules, such as perforin and granzyme, and cytokines, such as interferon ...

Chemokine receptors play a role in leukocyte recruitment, activation, and maintaining effector functions and regulate adaptive immune response and angiogenesis. The study aimed at flow cytometric analysis of T cell subsets with selected surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptor combination in peripheral blood of children with chronic kidney disease (CKD) on hemodialysis (HD). The percentage of T lymphocytes with CD8 and combined CD28,CCR7 expression was higher in HD children. The percentage of T lymphocytes expressing CCR7, CD28,CCR7, and CXCR4,CD8 was increased in children on conservative treatment. Total number (tn) of CXCR4+ cells was reduced in children on hemodialysis. The tn of T CXCR3+ cells was lower in children on conservative treatment. During HD the percentage of T CD4+ cells was higher and of T CXCR3+ lymphocytes was lower after HD session as compared to 15 min of session duration. During HD tn of T cells with expression of CCR4, CCR5, CCR7, CXCR3,

The contribution of inflammation to the development of fibrosis varies in different conditions, and understanding the interaction between these processes is relevant to devise therapeutic strategies for chronic diseases such as pancreatitis. Identification of the chemokine system has elucidated the molecular mechanisms regulating leucocyte trafficking in a given tissue. Chemokines are a family of small cytokines that exert gradient dependent chemoattraction of cells bearing specific cognate receptors. The chemokine system is considerably complex, as indicated by the high number of ligands and receptors, and by the fact that the same chemokine may bind more than one receptor and the same receptor more than one chemokine.2 Additionally, the effects of chemokines are not limited to inflammation as the majority of cells express at least one chemokine receptor. A related aspect of chemokine biology is the distinction between homeostatic and inflammatory chemokines, where expression of the latter ...

The therapeutic goal in autoimmune diseases such as RA is to control disease, to establish remission, and eventually to cure. In theory, this goal can be achieved using either Ag-specific approaches, for example, elimination of self-reactive T cells (assuming that a finite number of key Ags can be identified as the target of the autoimmune process in RA), or the non-Ag-specific approaches, for example, blockade of cytokines as in the case of TNF-a neutralization. Currently, only the latter types of approaches have yielded clinical benefit, and it is in this category that approaches to block chemokines or receptors may be included. Despite their appeal in terms of effectiveness, non-Ag-specific approaches carry a higher risk of immunosuppression and opportunistic infections (48).. Although there is a myriad of ongoing clinical trials testing the effects of chemokine/receptor blockers in RA (Table 1), to date one cannot yet predict how many of the current targets will prove to be clinically ...

Dendritic cells are believed to be crititcal in both initiating and modulating immune responses (32). Central to their role as immune sentinels is their ability to capture, process, and transport Ag to secondary lymphoid tissues where they serve as potent APCs capable of stimulating T cells in T cell areas. Trafficking of both T cells and dendritic cells to lymphoid organs followed by precise microenvironmental localization is necessary for efficient immune surveillance and is thought to be directed by chemokines (12). 6Ckine, a recently discovered CC chemokine (13, 14, 15), has been shown to be expressed by HEV in lymph nodes (16, 17), is capable of rapidly triggering integrin binding to vascular ligands (18), and is a potent chemoattractant for T lymphocytes (14, 15, 16, 17, 19), making it a leading candidate for mediating T cell homing. 6Ckine is also expressed by endothelial cells in lymphatic venules (17), the major route of dendritic cell entry into lymph nodes (33), suggesting that it may ...

Chemokines are small immune system proteins mediating leukocyte migration and activation, and are important in many aspects of health and diseases. Some chemokines also have the ability to block HIV-1 infection by binding to the HIV-1 co-receptors CCR5 (CC chemokine receptor 5) and CXCR4 (CXC chemokine receptor 4). The first part of this work is to determine the mechanism of action of a human herpesvirus-8 encoded viral chemokine analog vMIP-II (viral macrophage inflammatory protein-II) by characterizing its interactions with endothelial surface glycosaminoglycans (GAGs) and cell surface receptors. Nuclear magnetic resonance (NMR), mutagenesis and molecular-docking were conducted and results show that vMIP-II tightly binds glycosaminoglycans using residues distributed along one face of the protein, such as R18, R46 and R48, and that there is a shift in the GAG binding site between the monomer and dimer form of vMIP-II where the N-terminus is involved in GAG binding for the dimer. This study, for ...

Selective expression of chemokine receptors during T-cell polarization. Pathway based on Biocarta pathway (M4047). https://cgap.nci.nih.gov/Pathways/BioCarta/h_nktPathway The polarization of T cells into Th1 and Th2 cells is associated with their expression of subsets of chemokine receptors. While not being exposed to antigens, naïve T cells express CXCR4 and CCR7 receptors. TGF-beta van induce semi-naive T cells, that express a subset of CCR4 and CCR7 receptors. Th1 express CXCR3, CCR1, CCR2 and CCR5 receptors, while Th2 express CCR2, CCR3 and CCR5. However these subsets are not absolute as there is overlap between the expression of receptor subsets and thus between Th1 and Th2 cells ...

Clone REA685 recognizes the mouse CD197 (CCR7) antigen, a chemokine receptor for chemokines CCL19 and CCL21. CD197, like other chemokine receptors has seven transmembrane spanning domains and signals via G proteins. Expression of CD197 is found on semi-mature and mature dendritic cells (DCs), naive B and T cells, regulatory T (Treg) cells, a subpopulation of T cells called central memory T cells, and non-immune malignant cells. CD197 is involved in regulating homing of immune cells, immunity to pathogens, immune tolerance, development and function of Tregs, and manifestation of autoimmunity. Additional information: Clone REA685 displays negligible binding to Fc receptors. - Latvija

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Use of cell adhesion inhibitor for the mobilization of antigen presenting cells and immune cells in a cell mixture (AIM) from the peripheral blood and methods of use - Disclosed is a method to recover an antigen presenting cells (APCs) and immune cells rich mixture (AIM) from peripheral blood mononuclear cells (PBMC) mobilized with one or more cell adhesion inhibitors for the preparation of an AIM vaccine or an AIM adoptive immunotherapy preparation. In addition, AIM mobilization can be enhanced by priming, simultaneously or in sequence, one or more of a combination of different chemical compounds, cytokines, hormones, growth factors, etc. The interaction of chemokines and chemokine receptors enable tumor cells attachment or in close proximity to antigen presenting cells and immune cells which possess similar receptors in a micro niche environment. Severing the chemokine/chemokine receptor linkage by a cell adhesion inhibitor will release these specifically primed cell mixtures into the ...

There is growing evidence that inflammation and infection play important roles in the etiology of prostate cancer. As the chemokine network is directl

Immunology lecture on chemokines, chemokine receptor profiles, kinin and clotting system, fibrinolytic system, neutrophils, acute and chronic inflammation and NSAIDs.

Peptide sequence is < 50 % identical to other mouse chemokine receptors in this region. The antibody recognizes mouse CCR8 and was not tested for cross-reactivity to human CCR8.

The IUPHAR/BPS Guide to Pharmacology. CXCR1 - Chemokine receptors. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.

A number of the investigative efforts on chemokines have focused on intracellular signaling. Data from studies indicate that stimulation of chemokine receptors results in the activation of a variety of effector molecules.

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The 1990s brought a burst of information regarding the structure, expression pattern, and role in leukocyte migration and adhesion of chemokines and their receptors. At that time, the FDA approved the first therapeutic antibodies for cancer treatment. A few years later,it was reported that the chemokine receptors CXCR4 and CCR7 were involved on directing metastases to liver, lung, bone marrow, or lymph nodes, and the over-expression of CCR4, CCR6, and CCR9 by certain tumors. The possibility of inhibiting the interaction of chemokine receptors present on the surface of tumor cells with their ligands emerged as a new therapeutic approach. Therefore, many research groups and companies began to develop small molecule antagonists and specific antibodies, aiming to neutralize signaling from these receptors. Despite great expectations, so far, only one anti-chemokine receptor antibody has been approved for its clinical use, mogamulizumab, an anti-CCR4 antibody, granted in Japan to treat refractory ...

Carcinoma, Thyroid, Thyroid Carcinoma, Tumors, Association, Tumor, Discrimination, Patients, Cancer, Metastasis, Mutation, Phenotype, Staining, Human, Ptc, Cxc Chemokine Receptor, Cxc Chemokine Receptor 4, Galectin, Galectin-3, Behavior

This antimicrobial gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. Similar to other chemokines the protein encoded by this gene inhibits hemopoiesis and stimulates chemotaxis. This protein is chemotactic in vitro for thymocytes and activated T cells, but not for B cells, macrophages, or neutrophils. The cytokine encoded by this gene may also play a role in mediating homing of lymphocytes to secondary lymphoid organs. It is a high affinity functional ligand for chemokine receptor 7 that is expressed on T and B lymphocytes and a known receptor for another member of the cytokine family (small inducible cytokine A19). [provided by RefSeq, Sep 2014 ...

Our research focuses in understanding the roles of the G protein-couple receptors (GPCRs)and their mechanisms of action in inducing the migration of cells and disruption of cell adhesion. Both processes are important to lead cells to metastasis and cancer. GPCRs are the largest family of molecules located in the surface of the cell and responsible for transmitting signal from outside to the inside of the cell. Recently some of these receptors have emerged as crucial players in tumor growth and metastasis. Malignant cells often hijack the normal functions of these receptors in order to survive, proliferate autonomously and invade their surrounding tissues. Our group investigates the mechanism of action of one GPCR receptor, the chemokine receptor CCR2. This receptor is involved in different diseases associated with inflammation as well as in processes like cancer. Our goal is to discern to its mechanism of action. For this during these two years we have been studying the molecules associated with ...

Nck coprecipitation with ADAP.Formation of a complex containing ADAP and Nck is increased after stimulation via TCR or chemokine receptor. Immunoprecipitation o

TY - JOUR. T1 - CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. T2 - Absence of CCR2 shifts the Leishmania major - Resistant phenotype to a susceptible state dominated by Th2 cytokines, B cell outgrowth, and sustained neutrophilic inflammation. AU - Sato, Naoko. AU - Ahuja, Sunil K. AU - Quinones, Marion. AU - Kostecki, Vannessa. AU - Reddick, Robert L.. AU - Melby, Peter C.. AU - Kuziel, William A.. AU - Ahuja, Seema S. PY - 2000/7/17. Y1 - 2000/7/17. N2 - There is growing evidence that chemokines and their receptors regulate the movement and interaction of antigen-presenting cells such as dendritic cells (DCs) and T cells. We tested the hypothesis that the CC chemokine receptor (CCR)2 and CCR5 and the chemokine macrophage inflammatory protein (MIP)-1α, a ligand for CCR5, influence DC migration and localization. We found that deficiency of CCR2 but not CCN5 or MIP-1α led to distinct defects in DC ...

Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant

TY - JOUR. T1 - Human peripheral blood dendritic cells and monocyte subsets display similar chemokine receptor expression profiles with differential migratory responses. AU - Cravens, P. D.. AU - Hayashida, K.. AU - Davis, L. S.. AU - Nanki, T.. AU - Lipsky, P. E.. PY - 2007/6. Y1 - 2007/6. N2 - Human antigen presenting cells (APC) found in peripheral blood are considered to be precursors that have been released from the bone marrow and are in transit to the peripheral tissues. These APC populations include myeloid dendritic cells (mDC), plasmacytoid DC (pDC) and monocytes (Mo). To assign specialized functional roles and stages of development for APCs, CD33 expressing APC subsets were examined for their capacity to respond to chemokines. Three major CD33+ subsets including CD33brightCD14 bright Mo, CD33brightCD14- CD11c+ mDC and CD33dimCD14- pDC were present. Dendritic cells subsets and Mo expressed low levels of CC and CXC receptors, but distinctive chemokine receptor expression profiles were ...

Several elegant models of AAD have been described whereby transfer of in vitro-polarized Th2 cells induces pulmonary eosinophilia 18,19,20,21. However, the Th cells used for these studies were, in general, polarized for short times in culture. Therefore, we set out to develop a system whereby Th cells were maximally polarized to ensure differential chemokine receptor expression, and thus induced multiple pathophysiological endpoints after transfer in vivo. Th2 or Th1 cells were generated in vitro after several rounds of polarizing cytokines before transfer in vivo, when mice received multiple serial in vivo antigen challenges. Accordingly, Th1 or Th2 cells were transferred intravenously to unsensitized BALB/c recipient mice, and changes in lung function were measured at various time intervals after antigen challenge. Mice were then killed at day 4 or 7, and the extent of inflammation was determined in the BAL and tissue (Fig. 1). Control mice that received cells but no antigen challenge showed ...

Monocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers. CCR9 expression on PB monocytes/macrophages was analysed by flow cytometry and in synovium by immunofluorescence. Chemokine receptor CCR9 mRNA expression was examined in RA and non-RA synovium, monocytes/macrophages from PB and synovial fluid (SF) of RA patients and PB of healthy donors using the reverse transcription polymerase chain reaction (RT-PCR). Monocyte differentiation and chemotaxis to chemokine ligand 25 (CCL25)/TECK were used to study CCR9 function. CCR9 was expressed by PB monocytes/macrophages in RA and healthy donors, and increased in RA. In RA and non-RA synovia,

INTRODUCTION: Monocytes/macrophages accumulate in the rheumatoid (RA) synovium where they play a central role in inflammation and joint destruction. Identification of molecules involved in their accumulation and differentiation is important to inform therapeutic strategies. This study investigated the expression and function of chemokine receptor CCR9 in the peripheral blood (PB) and synovium of RA, non-RA patients and healthy volunteers. METHODS: CCR9 expression on PB monocytes/macrophages was analysed by flow cytometry and in synovium by immunofluorescence. Chemokine receptor CCR9 mRNA expression was examined in RA and non-RA synovium, monocytes/macrophages from PB and synovial fluid (SF) of RA patients and PB of healthy donors using the reverse transcription polymerase chain reaction (RT-PCR). Monocyte differentiation and chemotaxis to chemokine ligand 25 (CCL25)/TECK were used to study CCR9 function. RESULTS: CCR9 was expressed by PB monocytes/macrophages in RA and healthy donors, and increased in

In Response: We read with interest Dr. von Luettichaus letter about the expression of chemokine receptors in osteosarcoma patient samples. They analyzed chemokine receptor expression in osteosarcoma tumor samples following microdissection. Their results showed that infiltrating cells and not the tumor cells per se represented the major source of expression of chemokine receptors, including CXCR4.. However, other data suggest that the osteosarcoma cells are expressing CXCR4 and other chemokine receptors. We previously analyzed the chemokine receptor expression by real-time PCR in different osteosarcoma cell lines. CXCR4 was expressed in two cell lines, U2OS and HOS, as reported by others (1-3). In their recent study, Kim et al. reported that K7M2 murine osteosarcoma cell lines expressed CXCR4. The cells were treated in vitro with a CXCR4 inhibitor (CTCE-9908). They observed a decrease in the proliferative rate, an increase in apoptosis, and a decrease in adhesion to extracellular matrix ...

Chemokines promote leukocyte migration through the activation of dedicated G-protein coupled receptors. Beyond conventional chemokine receptors, which directly induce cell migration through heterotrimeric Gαi-mediated signalling events, a set of atypical chemokine receptors (ACKRs) have been described. ACKRs do not activate Gαi-mediated signalling activity, but they are mainly involved in shaping the chemokine gradient. The best characterized member of this family is ACKR2. ACKR2, previously referred to as D6, is a scavenger receptor that binds with high affinity to 13 inflammatory CC chemokines. The scavenging activity of ACKR2 relies on its intracellular traffic properties. Under homeostatic conditions, ACKR2 is mainly localized in intracellular stores associated with both early Rab4/5-positive and recycling Rab11-positive endosomes. At increasing levels of chemokines, ACKR2 increases plasma membrane abundance through an acceleration in the rate of Rab11-depedent recycling pathway, in order ...

CXCR4 is a member of the chemokine receptor subfamily of seven transmembrane domained, G-protein coupled receptors, whose sole known natural ligand is CXCL12/SDF-1. CXCR4 is an unusual chemokine receptor by virtue of having expanded roles beyond leukocyte recruitment, including fundamental processes such as the development of the hematopoietic, cardiovascular, and nervous systems during embryogenesis. The receptor was first discovered as one of the co-receptors for HIV, and thereafter was also found to be expressed by multiple cancers including breast, prostate, lung, colon and multiple myeloma. A number of recent studies have correlated high levels of CXCR4 expression in cancers with poor prognosis and with resistance to chemotherapy, in part through enhancing interactions between cancers and stroma. A possible role for CXCR4, and chemokine receptors generally, in cancer and metastasis was first suggested in studies of breast cancer, showing that the receptor plays a role in directing metastatic cells

Maintenance and restoration of endothelial integrity are critical for blood vessel function. Endothelial cells (EC) form a monolayer in the inner surfaces of blood vessels that controls exchange of metabolites and regulates coagulation and cell trafficking. Cardiovascular diseases, such as atherosclerosis, vascular interventions, or bypass surgery, cause EC damage or overt defects in the endothelial monolayer, which triggers vascular inflammation, neointima formation, and ultimately vessel obstruction if endothelial integrity is not restored (Gimbrone & Garcia‐Cardena, 2016).. Under physiological conditions, EC replication is inhibited by cell contact and laminar flow (Akimoto et al, 2000; Chen et al, 2000). The loss of few cells is repaired rapidly by extension and spreading of adjacent EC without the need for proliferation (Reidy & Schwartz, 1981). However, larger EC lesions require proliferation to regenerate the endothelial monolayer and prevent neointima formation (Haudenschild & ...

The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy. Receptors for osteoclastogenic factors (CD115 and receptor activator of nuclear factor-κB [RANK]) and selected chemokines (CC chemokine receptor 1 [CCR1], CCR2, CCR4, CXC chemokine receptor 3 [CXCR3], CXCR4) were determined in an OCP-rich subpopulation (CD3−CD19−CD56−CD11b+CD14+) by flow cytometry. In parallel, levels of CC chemokine ligand 2 (CCL2), CCL3, CCL4, CCL5, CXC chemokine ligand 9 (CXCL9), CXCL10, and

Naïve T cells, when activated by specific antigen and cytokines, up-regulate adhesion molecules as well as chemokine receptors on their surface, which allows them to migrate to inflamed tissues. Human studies have shown that CXCR3 is one of the chemokine receptors that is induced during T cell activation. Moreover, CXCR3-positive T cells are enriched at inflammatory sites in patients with autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. In this study, we use a mouse model of inflammation to demonstrate that CXCR3 is required for activated T cell transmigration to inflamed tissue. Using an anti- mCXCR3 antibody, we have shown that in vitro-differentiated T helper (Th) 1 and Th2 cells up-regulated CXCR3 upon stimulation with specific antigen/major histocompatibility complex. However, only Th1 cells, when adoptively transferred to syngeneic recipients, are efficiently recruited to the peritoneum in an adjuvant-induced peritonitis model. Furthermore, the neutralizing anti-mCXCR3

Human and murine CCR8 are homologous G protein-coupled receptors whose reported ligands include human I-309, thymus and activation-regulated chemokine (TARC), macrophage inflammatory protein (MIP)-1β, TCA3, and liver-expressed chemokine (LEC; references (34)(35)(36)(37)). In addition, the virally encoded chemokines, vMIP-I and vMIP-II, can also bind CCR8 (38)(39)(40). The selective expression of CCR8 in Th2 T cells (11)(12) suggests that it may have an important role in the function of these cells. However, there are currently no experimental data demonstrating such a role. To investigate this possibility, and to study other potential functions of CCR8, we have generated and analyzed CCR8-deficient mice. Using models of Th2 (schistosomal) cell-mediated immune responses as well as two models of Th2-mediated allergic airway disease, we show impairment of Th2 type cytokine expression and eosinophil mobilization in CCR8−/− mice. This defect was specific to the in vivo Th2 type response, as the ...

Purpose: The naïve cornea is endowed with distinct populations of antigen-presenting cells (APCs), whose number increases significantly during inflammation. This recruitment of APCs to the cornea during inflammation is mediated, in part, by chemokine receptors as part of the multistep adhesion cascade. The purpose of this study is to identify the chemokine pathways involved in the recruitment of conventional dendritic cells (cDCs) to the cornea during inflammation.. Methods: A murine corneal suture model for inflammation was used. Wild-type (WT) BALB/c mice received 3 interrupted stromal sutures (nylon 11-0). Seven days later, 20 millions cDCs labeled with a green fluorescent marker (CFDA) were adoptively transferred intravenously (IV) via tail vein injection. These cDCs were harvested from spleens of mice that received subcutaneous FLT3-expressing melanoma cells. 30 minutes before adoptive transfer of cDCs, WT BALB/c were blocked with 50 mg/mL IV of neutralizing monoclonal antibody (MAb) ...

Jafarnejad M, Zawieja DC, Brook BS, Nibbs RJB, Moore JEet al., 2017, A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4., J Immunol, Vol: 199, Pages: 2291-2304 The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations. The mechanisms underpinning the establishment and regulation of these gradients are poorly understood. In this article, we have incorporated multiple biochemical processes describing the CCL19-CCL21-CCR7-ACKR4 network into our model of LN fluid flow to establish a computational model to investigate intranodal chemokine gradients. Importantly, the model recapitulates CCL21 gradients ...

Negative Binding Cooperativity within CCR2/CCR5 Heterodimers. We next tested further the pharmacological properties of CCR5/CCR2 heterodimers using binding assays. We demonstrated previously that CCR2/CCR5 heterodimers can only bind a single chemokine with high affinity (El Asmar et al., 2005). These observations suggested either an overlap between the two chemokine binding sites of the monomers or some kind of negative allosteric interaction across the dimer interface (Springael et al., 2005). It was also shown for another class I receptor (TSHr) that a single ligand molecule binds to a receptor dimer (Urizar et al., 2005), and a similar observation has been made recently for a receptor belonging to class 3 (Kniazeff et al., 2004; Urizar et al., 2005). To determine more precisely the mechanism underlying these effects, we built on the model of chemokine receptor dimers and performed dissociation kinetics experiments after extensive ligand dilution, a procedure that constitutes the classic way ...

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GPR-9-6 is a chemokine receptor for TECK. (A) GPR-9-6 transfectants were examined for chemotactic responses to various concentrations of TECK and I-TAC ranging

This gene encodes a multi-pass membrane protein that belongs to the CXC chemokine receptor family. It is expressed in mature B-cells and Burkitts lymphoma. This cytokine receptor binds to B-lymphocyte chemoattractant (BLC), and is involved in B-cell migration into B-cell follicles of spleen and Peyer patches. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011 ...

ZK-756326 is a potent, selective and non-peptide CCR8 chemokine receptor agonist. ZK 756326 inhibited the binding of the CCR8 ligand I-309 (CCL1), with an IC(50) value of 1.8 muM. ZK 756326 was a full agonist of CCR8, dose-responsively eliciting an increase in intracellular calcium and cross-desensitizing the response of the receptor to CCL1.

Chemokine Receptors: Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif.

cytoplasm, external side of plasma membrane, extracellular exosome, extracellular space, plasma membrane, chemoattractant activity, chemokine activity, chemokine receptor binding, CXCR chemokine receptor binding, adult locomotory behavior

PLC-, PKC-, and calcium-induced calcium release from ryanodine-sensitive calcium stores signaling pathways are involved in CCL2- and CXCL1-induced CGRP release from primary nociceptive neurons, in which chemokines produce painful effects via direct actions on chemokine receptors expressed by nociceptive neurons ...

Biased agonism, the ability of different ligands for the same receptor to selectively activate some signaling pathways while blocking others, is now an established paradigm for G protein-coupled receptor signaling. One group of receptors in which endogenous bias is critical is the chemokine system, consisting of over 50 ligands and 20 receptors that bind one another with significant promiscuity. We have previously demonstrated that ligands for the same receptor can cause biased signaling responses. The goal of this study was to identify mechanisms that could underlie biased signaling between different receptor splice variants. The C-X-C motif chemokine receptor 3 (CXCR3) has two splice variants, CXCR3A and CXCR3B, which differ by 51 amino acids at its N-terminus. Consistent with an earlier study, we found that C-X-C motif chemokine ligands 4, 9, 10, and 11 all activated Gαi at CXCR3A, while at CXCR3B these ligands demonstrated no measurable Gαi or Gαs activity. β-arrestin (βarr) was ...

The research interest of my group remains focused on Chemokine activities in physiology and pathology, with an emphasis on the mechanisms governing fine-tuning modulation of their expression and activity. Chemokines are secreted proteins and have emerged as key controllers of integrin function and cell locomotion. The effects of chemokines are mediated by seven transmembrane domain receptors coupled to GTP-binding proteins, which are differentially expressed in a wide range of cell types. The resulting combinatorial diversity in responsiveness to chemokines guarantees the proper tissue distribution of distinct leukocyte subsets under normal and inflammatory/pathological conditions. A vast range of in situ experiments, aimed at understanding which chemokines are produced in specific circumstances, has revealed that a variety of chemokines can be concomitantly produced at target sites of leukocyte trafficking and homing. This renders the chemokine system a good target for therapy, and has ...

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BioAssay record AID 52555 submitted by ChEMBL: Compound was tested in vitro for inhibition of [125I]RANTES binding to THP-1 cell membranes rich in C-C chemokine receptor type 1.

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.

AYOXXA launches LUNARISTM Human and Mouse Chemokine Kits to explore chemokine signaling LUNARISTM Chemokine Kits are validated for the quantitative analysis of

When two chemokine receptors in the brain interact, leukemic cells (stained green) creep out of a small vein in the membrane covering the brain of a mouse and enter the cerebrospinal fluid. The chemokine CCL19, which is in the endothelium lining the vein, is stained blue in this immunofluorescent image.

Novel human chemokine receptors, MCP-1RA and MCP-1RB, and processes for producing them are disclosed. The receptors, which are alternately spliced versions of MCP-1 receptor protein may be used in an assay to identify antagonists of MCP-1 which are therapeutically useful in the treatment of atherosclerosis and other diseases characterized by monocytic infiltrates.

From NCBI Gene: This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. [provided by RefSeq, Jul 2013]

RayBio|sup|®|/sup| C-Series Human Chemokine Antibody Array 1 Kit. Detects 38 Human Chemokines. Suitable for all liquid sample types.

Emeson, E E., Bcg and c. Parvum enhance selective recruitment of specifically reactive t-lymphocytes. Abstr. (1977). Subject Strain Bibliography 1977. 2521 ...

Principal Investigator：NOJIMA Yoshihisa, Project Period (FY)：1997 - 1998, Research Category：Grant-in-Aid for Scientific Research (B), Section：一般, Research Field：内科学一般

FlowRepository is a public database of flow cytometry experiments where you can query and download data collected and annotated according to the MIFlowCyt standard. It supports storage, annotation, analysis, and sharing of flow cytometry datasets.

Cytokine or chemokine encoded by a viral vector is currently regarded as a promising way of cancer gene immunotherapy. Researchers have paid attention to chemotactic activity of chemokines for immune cells and expected that they may be able to play an important role in cancer treatment, because the basis and premise of immunotherapy is the accumulation of immune cells in tumor tissues.. The CC chemokine ILC, also called cutaneous T cell-attracting chemokine or CCL27, was reported to recruit T cells to the site of its injection (27) . The CX3C family chemokine FKN (also called CX3CL1) could also attract a variety of cytotoxic lymphocytes (13 , 14 , 28) and enhance the cytotoxicity of NK cells (29) . In the present study, we hypothesized that the transfer of the mILC or mFKN gene to tumor cells, by using recombinant adenovirus in vitro, could render the tumor to express the chemokine in vivo. The chemokine would consequently induce the accumulation of immune cells in the tumor tissue and initiate ...

The table below shows the top 100 pain related interactions that have been reported for chemokine receptor transport out of membrane raft. They are ordered first by their pain relevance and then by number of times they were reported for chemokine receptor transport out of membrane raft. Please click on the INT link to display more detailed information on each interaction. ...

2MLO: Structural basis for the binding of the membrane-proximal C-terminal region of chemokine receptor CCR2 with the cytosolic regulator FROUNT

Fast, simple luminescent calcium flux assays using an AequoScreen cell line stably-transfected with human chemokine XCR1 receptor.

Fingerprint Dive into the research topics of Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells. Together they form a unique fingerprint. ...

Asthma affects almost 20 million people in the United States and more than 300 million people worldwide. Of these, 10-15% have severe asthma, which is refractory to commonly available drugs. New drugs are needed because those that are currently available cannot control symptoms and exacerbations in all patients and can cause adverse reactions. In the past 10 years, there have been substantial advances in the understanding of asthma genetics, airway biology, and immune cell signaling. These advances have led to the development of small molecule therapeutics and biologic agents that may improve asthma care in the future. Several new classes of asthma drugs-including ultra long acting β agonists and modulators of the interleukin 4 (IL-4), IL-5, IL-13, and IL-17 pathways-have been evaluated in randomized controlled trials. Other new drug classes-including dissociated corticosteroids, CXC chemokine receptor 2 antagonists, toll-like receptor 9 agonists, and tyrosine kinase inhibitors-remain in ...

This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. The gene

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