• Here, we investigate the effect of an orthosteric and an allosteric antagonist on CCR2 dynamics by coupling long-timescale molecular dynamics simulations with Markov-state model theory. (iasp-pain.org)
  • 2020 ) An Agonist Dependent Allosteric Antagonist of Prostaglandin EP2 Receptors. (neurotree.org)
  • 2020 ) Potent, selective, water soluble, brain-permeable EP2 receptor antagonist for use in central nervous system disease models. (neurotree.org)
  • Cenicriviroc (CVC) is an oral CCR2/CCR5 antagonist in Phase 3 development for NASH. (diabetesjournals.org)
  • CCL7 binds to CCR1, CCR2, and CCR3 receptors and appears to be an antagonist for the CCR5 receptor. (qedbio.com)
  • In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradually returned to control (uninjured) levels by 14 days. (cdc.gov)
  • To dissect the role of these chemokines, additional studies were conducted in CCR5- and CCR2-deficient mice. (cdc.gov)
  • Cenicriviroc, a drug that blocks both CCR5 and CCR2 receptors on immune cells, was associated with a decrease in liver fibrosis in people with non-alcoholic steatosis, a type of fatty liver disease, according to a report in the August 17 online edition of Hepatology . (hivandhepatitis.com)
  • Injection of CCR2 lentiviruses restored CCR2 expression and functions in monocytes. (nih.gov)
  • CCR2 surface expression on blood monocytes changes in a time-of-day-dependent manner (being higher at the beginning of the active phase) and affects monocytes recruitment in tissues including the heart. (wikipedia.org)
  • MCP1 binds to a protein on the surface of monocytes called the CCR2 receptor, stimulating the cells to travel to the injury site and launch inflammation. (world.edu)
  • Without that receptor, the monocytes do not respond to MCP1, so in theory, the treatment should block much of the inflammatory response. (world.edu)
  • The researchers reduced metastases by using a compound that blocks CCR2, a receptor on the surface of the inflammatory monocytes. (futurity.org)
  • CD163, a scavenger receptor that serves as an M2 macrophage phenotype marker, is also expressed on monocytes, and binds to haptoglobin-hemoglobin complexes, mediating their endocytosis [ 11 ]. (biomedcentral.com)
  • This gene encodes two isoforms of a receptor for monocyte chemoattractant protein-1 (CCL2), a chemokine which specifically mediates monocyte chemotaxis. (wikipedia.org)
  • suggest that CCR2 signaling may have a direct role in human cognition, partly because expression of CCR2 was associated with the ApoE haplotype (previously associated with Alzheimer's disease), but also because CCL2 is expressed at high concentrations in macrophages found in atherosclerotic plaques and in brain microglia. (wikipedia.org)
  • Knockdown by AAV9-TRAF6-RNAi improved spatial learning and memory, decreased TUNEL-positive cell number in injured cortex, and downregulated expression levels of p-NF-κB, p-JNK, p-ERK, p-p38, CCL2, CCR2, CXCL1, and CXCR2 post-TBI. (researchsquare.com)
  • Our preliminary study found that CCL2 was mainly co-localized with the astroglial marker glial fibrillary acidic protein (GFAP), while the CCL2 receptor chemokine C-C motif receptor 2 (CCR2) was mainly co-localized with the neuronal nuclear marker NeuN in TBI model rats, suggesting that CCL2‒CCR2 signaling is a major driver of neuroinflammation, neurodegeneration, and concomitant motor and cognitive dysfunction following TBI [9]. (researchsquare.com)
  • Chemokines and chemokine receptors, especially the CCL2/CCR2 pathway, are involved in this interaction. (jostchemical.com)
  • Functional annotation clustering of the microarray data showed that gene clusters involved in immune and antiviral responses ranked highly, involving genes such as chemokine (C-C motif) ligand 2 ( CCL2 ), chemokine (C-C motif) ligand 5 ( CCL5 ), chemokine (C-X-C motif) ligand 10 ( CXCL10 ), and toll like receptor 3 ( TLR3 ). (molvis.org)
  • Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India. (cdc.gov)
  • To investigate the effect of hyperglycemia on anti-tumor function induced by anti-PD-1 antibody treatment, we treated STZ-induced diabetic mice with subcutaneous MC38 colon carcinoma tumors with anti-PD-1 antibody, and examined changes in tumor growth, the number of tumor-infiltrating immune cells, and the expression of chemokines and chemokine receptors. (nature.com)
  • Interestingly, CCR1 and CXCR6 were expressed mainly on less differentiated NKG2A+ CD56dim NK cells (B). Next, we stratified the chemokine receptor expression on mature KIR+ NK cells based on the expression of self (educated) or non-self KIR (uneducated). (confex.com)
  • These class A G-protein coupled receptors (GPCRs) are involved in mammalian signaling pathways and control cell migration toward endogenous CC chemokine ligands, named for the adjacent cysteine motif on their N terminus. (iasp-pain.org)
  • A gene expression array showed significantly increased expression of CCR3, a receptor of eotaxin-3, in PC-3. (cancerindex.org)
  • CCR3 (C-C chemokine receptor type 3 or eosinophil eotaxin receptor) is a receptor for a C-C type chemokine and binds to eotaxin, eotaxin-3, MCP-3, MCP-4, RANTES and MIP-1 delta. (multispaninc.com)
  • Hence, CCR3 is closely associated with asthma and allergy and blockade of this receptor may have pronounced beneficial effects in these diseases. (multispaninc.com)
  • 2002) Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. (multispaninc.com)
  • Disease progression was exacerbated in APP(Swe)/PS1 mice (transgenic mice expressing a chimeric amyloid precursor protein [APPSwe] and human presenilin 1 [PS1]) harboring CCR2-deficient BMCs. (nih.gov)
  • C-C chemokine receptor type 2 (CCR2 or CD192 (cluster of differentiation 192) is a protein that in humans is encoded by the CCR2 gene. (wikipedia.org)
  • Interferon pathway-related cytokines/chemokines, including interleukin (IL) 18, macrophage inflammatory protein 3α, and IL-33, were elevated, but tumor necrosis factor-α, IL-6, CXCL8 (formerly IL-8), and cytokines acting through C-C chemokine receptor 2 and CCR5 were lower among case-patients than controls. (cdc.gov)
  • Chemokines receptors are seven transmembrane spanning G protein-coupled receptors that allow cells to migrate towards increasing chemokine gradients. (biolegend.com)
  • Many biologically active molecules signal via membrane-bound receptors coupled to heterotrimeric G proteins, and are therefore referred as G protein-coupled receptors (GPCR). (europa.eu)
  • The protein encoded by this gene is a receptor for C-C type chemokines. (cancerindex.org)
  • It belongs to family 1 of the G protein-coupled receptors. (cancerindex.org)
  • CD192, also known as CCR2, is a 42 kD G-protein coupled receptor that is associated with bone marrow homeostasis. (biolegend.com)
  • Specifically, CD192 mediates monocyte chemotaxis and acts as a receptor for monocyte chemoattractant protein 1 (MCP-1). (biolegend.com)
  • G-protein-coupled receptor, 7-transmembrane protein, 42 kD. (biolegend.com)
  • The receptor N-terminus is external and contributes to ligand binding while the carboxy terminus (COOH) allows for interaction with signaling molecules and downstream signaling. (biolegend.com)
  • Structural basis for ligand modulation of the CCR2 conformational landscape. (iasp-pain.org)
  • JNK1 plays an important role in osteoclastogenesis in response to the osteoclastogenic cytokine receptor activator for nuclear factor-κB ligand (RANKL). (bvsalud.org)
  • This work demonstrates for the first time that nLDL acts in synergy with LPS to alter the balance of human monocyte subsets and their ability to produce inflammatory cytokines and chemokine receptors with prominent roles in atherogenesis. (nih.gov)
  • Monocyte recruitment/infiltration into the liver is mediated by C-C chemokine receptor 2 (CCR2). (diabetesjournals.org)
  • Interferon pathway activation and cytokines/chemokines acting through CCR2 and CCR5 improved health results among children with severe CCHF. (cdc.gov)
  • We find that the antagonists shift CCR2 into several stable inactive conformations that are distinct from the crystal structure conformation and disrupt a continuous internal water and sodium ion pathway, preventing transitions to an active-like state. (iasp-pain.org)
  • Without antagonists, the apo dynamics reveal intermediate conformations along the activation pathway that provide insight into the basal dynamics of CCR2 and may also be useful for future drug design. (iasp-pain.org)
  • Finally, gene therapy using a lentivirus-expressing CCR2 transgene in BMCs prevented cognitive decline in this mouse model of AD. (nih.gov)
  • The presence of these cells in the brain of non-irradiated APP(Swe)/PS1/CCR2⁻/⁻ mice supports the concept that they can be used as gene vehicles for AD. (nih.gov)
  • This CCR2 gene is located in the chemokine receptor gene cluster region. (wikipedia.org)
  • The receptors encoded by this gene mediate agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. (wikipedia.org)
  • This gene and seven other chemokine receptor genes form a chemokine receptor gene cluster on the chromosomal region 3p21. (cancerindex.org)
  • One approach relies on the isolation and cloning of T cell receptors (TCRs) that confer non-reactive T cells with specific and potent immune function following gene transfer. (upenn.edu)
  • For this study, the researchers designed an RNA sequence that blocks the gene for the CCR2 receptor. (world.edu)
  • Toll-like receptor-3 gene polymorphism in patients with Japanese encephalitis. (cdc.gov)
  • 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). (cancerindex.org)
  • We combined the high-throughput of mass cytometry, facilitating the analysis of 57 twin pairs, with cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) of eight selected twin pairs to obtain a comprehensive overview of epitopes, transcriptome and T cell receptor (TCR) clonotypes. (nature.com)
  • This serves as a guidepost for rationally designing new combination checkpoint therapies, downstream T cell receptor (TCR) isolation, cancer antigen identification and molecular characterization of naturally occurring tumor-reactive T cells in human cancer. (upenn.edu)
  • Click on the receptor to sort the ligands to the top. (biolegend.com)
  • Chemokine receptors and their associated ligands are involved in a wide range of diseases and thus have become important drug targets. (iasp-pain.org)
  • While nLDL + LPS significantly increased the number of NCMs expressing IL-1 beta and the C-C chemokine receptor type 2 (CCR2), the amount of NCMs expressing the CX3C chemokine receptor 1 (CX3CR1) decreased. (nih.gov)
  • Interestingly, receptors which expression declines during NK cell differentiation (CCR5, CCR7, and CXCR3) are commonly associated with adaptive T cell responses to viruses, whereas receptors that are upregulated along the differentiation axis (CXCR1, CXCR2, CX3CR1, CMKLR1) are typical for neutrophils and macrophages as a part of the innate immune response. (confex.com)
  • The same study found that CCR2 expression was also associated with cognitive decline over 9-years in a sub-analysis on inflammatory related transcripts only. (wikipedia.org)
  • This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway. (cancerindex.org)
  • 2023 ) Pharmacological inhibition of the inflammatory receptor CCR2 relieves the early deleterious consequences of status epilepticus. (neurotree.org)
  • Delivering RNA specific to the CCR2 receptor avoids the side effects often seen with other anti-inflammatory drugs, Nahrendorf says, and allows other key immune cells to carry on with their normal functions. (world.edu)
  • Within the fat (adipose) tissue of CCR2 deficient mice, there is an increased number of eosinophils, greater alternative macrophage activation, and a propensity towards type 2 cytokine expression. (wikipedia.org)
  • CXCR4, CCR4, and CCR2 expression was relatively uniform across all subsets. (confex.com)
  • We found that the chemokine-induced migration capability of NK cells correlated closely with the expression level of corresponding chemokine receptor, leading to subset specific responses to various chemokine gradients (D). (confex.com)
  • Indeed, transplantation of CCR2-deficient BMCs enhanced the mnesic deficit and increased the amount of soluble Aβ and expression of transforming growth factor (TGF)-β1 and TGF-β receptors. (nih.gov)
  • CCR2 deficient mice have been shown to develop an accelerated Alzheimer's-like pathology in comparison to wild type mice. (wikipedia.org)
  • Muscle function and histological characteristics were monitored in injured mice that were genetically deficient for the CCR5 receptor (a major receptor for MIP-1alpha and MIP-1beta) and also rendered MCP-1 deficient with neutralizing antibodies. (cdc.gov)
  • Strength recovery was also impaired in mice deficient for the receptor of MCP-1, CCR2, but not in CCR5-/- mice that were not injected with MCP-1 antiserum. (cdc.gov)
  • All macrophages express common markers such as CD11b (Mac1 or CR3), CD68, and CD115 (M-CSF receptor). (hindawi.com)
  • By contrast, transplantation of wild-type bone marrow stem cells restored memory capacities and diminished soluble Aβ accumulation in APP(Swe)/PS1 and APP(Swe)/PS1/CCR2⁻/⁻ mice. (nih.gov)
  • The difference in observations between mice (CCR2 depletion causes cognitive decline) and humans (higher CCR2 associated with lower cognitive function) could be due to increased demand for macrophage activation during cognitive decline, associated with increased β-amyloid deposition (a core feature of Alzheimer's disease progression). (wikipedia.org)
  • found evidence of a relationship between expression of CCR2 and cognitive function (assessed using the mini-mental state examination, MMSE). (wikipedia.org)
  • Higher CCR2 expression was associated with worse performance on the MMSE assessment of cognitive function. (wikipedia.org)
  • 2020 ) Inhibition of the prostaglandin EP2 receptor prevents long-term cognitive impairment in a model of systemic inflammation. (neurotree.org)
  • Here we show that these mechanisms specifically require CC-chemokine receptor 2 (CCR2) expression in bone marrow cells (BMCs). (nih.gov)
  • Decreased CCR2 expression in bone marrow-derived microglia may therefore play a major role in the etiology of this neurodegenerative disease. (nih.gov)
  • Specific chemokine receptors are often required to gain entry (or exit) from certain organs and tissues like the thymus and bone marrow. (biolegend.com)
  • Another approach relies upon the use of chimeric antigen receptors (CARs) that directly target cancer cells or immunosuppressive cellular elements in the tumor microenvironment. (upenn.edu)
  • Tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling may promote post-TBI neuroinflammation, thereby exacerbating secondary injury. (researchsquare.com)
  • Second messenger signaling bypasses CGRP receptor blockade to provoke migraine attacks in humans. (medscape.com)
  • STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. (medsci.org)
  • It expresses a range of cell surface molecules involved in adaptive and innate immunity, as well as crucial sentinel molecules, including toll-like receptors (TLRs), which are pivotal in early cellular defense against virus infection. (molvis.org)
  • The human NK cell repertoire is functionally diversified through a tightly regulated differentiation process characterized by an early transition from CD56bright to CD56dim NK cells, followed by coordinated changes in expression of inhibitory receptors, including NKG2A and killer cell immunoglobulin-like receptors (KIR). (confex.com)
  • In order to delineate the homing patterns of distinct NK cell subsets, we used high-dimensional flow cytometry combined with functional assays to map the NK cell chemokine receptor expression and migratory behavior. (confex.com)
  • To determine whether the observed differences in chemokine receptor expression translate into altered chemokine responsiveness between the subsets, we combined the transwell system with multicolor flow cytometry. (confex.com)
  • The present results show that peripheral blood NK cell chemokine receptor profile changes in a coordinated fashion during NK cell differentiation and is further influenced by the expression of self-specific KIR. (confex.com)
  • Primary astrocytes were stimulated with LPS following TRAF6 siRNA or control transfection, and NF-κB, MAPKs, chemokine, and chemokine receptor expression levels evaluated by western blotting and ELISA. (researchsquare.com)
  • The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage subpopulations. (jci.org)
  • Patients with estrogen receptor α positive (ERα+) breast cancer can respond to endocrine therapy, but treatment resistance is common and associated with downregulation of ERα expression in the dormant residual cells. (bvsalud.org)
  • 2023 ) Phase 1 Clinical Results for NP10679, a pH-sensitive GluN2B-selective N-methyl-d-aspartate Receptor Inhibitor. (neurotree.org)
  • These cells expressed central nervous system-homing receptors, exhibited a dysregulated CD25-IL-2 axis, and their proliferative capacity positively correlated with MS severity. (nature.com)
  • ECM components (i.e., fibronectin or collagens) directly interact with membrane receptors (i.e., integrins), particularly, by influencing cell behavior. (springer.com)
  • 2023 ) Novel GluN2B-Selective NMDA Receptor Negative Allosteric Modulator Possesses Intrinsic Analgesic Properties and Enhances Analgesia of Morphine in a Rodent Tail Flick Pain Model. (neurotree.org)
  • This project aims to study the desensitisation of the chemokine receptors CCR2 and CCR5 in hematopoietic cells using a multidisciplinary approach. (europa.eu)
  • thick line: receptor-expressing cells. (multispaninc.com)