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Search results for: C C Chemokine Receptor 3 (CCR3)

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#37127541   2023/05/01 To Up

Cholesterol Biases the Conformational Landscape of the Chemokine Receptor CCR3: A MAS SSNMR-Filtered Molecular Dynamics Study.

Cholesterol directs the pathway of ligand-induced G protein-coupled receptor (GPCR) signal transduction. The GPCR C-C motif chemokine receptor 3 (CCR3) is the principal chemotactic receptor for eosinophils, with roles in cancer metastasis and autoinflammatory conditions. Recently, we discovered a direct correlation between bilayer cholesterol and increased agonist-triggered CCR3 signal transduction. However, the allosteric molecular mechanism escalating ligand affinity and G protein coupling is unknown. To study cholesterol-guided CCR3 conformational selection, we implement comparative, objective measurement of protein architectures by scoring shifts (COMPASS) to grade model structures from molecular dynamics simulations. In this workflow, we scored predicted chemical shifts against 2-dimensional solid-state NMR C-C correlation spectra of U-N,C-CCR3 samples prepared with and without cholesterol. Our analysis of trajectory model structures uncovers that cholesterol induces site-specific conformational restraint of extracellular loop (ECL) 2 and conserved motion in transmembrane helices and ECL3 not observed in simulations of bilayers with only phosphatidylcholine lipids. PyLipID analysis implicates direct cholesterol agency in CCR3 conformational selection and dynamics. Residue-residue contact scoring shows that cholesterol biases the conformational selection of the orthosteric pocket involving Y41, Y113, and E287. Lastly, we observe contact remodeling in activation pathway residues centered on the initial transmission switch, Na pocket, and R in the DRY motif. Our observations have unique implications for understanding of CCR3 ligand recognition and specificity and provide mechanistic insight into how cholesterol functions as an allosteric regulator of CCR3 signal transduction.
Evan J van Aalst, Corey J McDonald, Benjamin J Wylie

1717 related Products with: Cholesterol Biases the Conformational Landscape of the Chemokine Receptor CCR3: A MAS SSNMR-Filtered Molecular Dynamics Study.

50ug 100ul100.00 ul100 100.00 ul1 ml

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#36998150   // To Up

Chemokine CCL7 mediates trigeminal neuropathic pain CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice.

Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to contribute to neuropathic pain via astrocyte-microglial interaction in the spinal cord. Whether CCL7 in the trigeminal ganglion (TG) involves in trigeminal neuropathic pain and the involved mechanism remain largely unknown.
Lin-Peng Zhu, Meng-Lin Xu, Bao-Tong Yuan, Ling-Jie Ma, Yong-Jing Gao

2080 related Products with: Chemokine CCL7 mediates trigeminal neuropathic pain CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice.

2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box100 μg50ug100 μg2 Pieces/Box2 Pieces/Box8 inhibitors2 Pieces/Box2 Pieces/Box

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#36982260   2023/03/08 To Up

Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement.

Aging drives cognitive decline, and mitochondrial dysfunction is a hallmark of age-induced neurodegeneration. Recently, we demonstrated that astrocytes secrete functional mitochondria (Mt), which help adjacent cells to resist damage and promote repair after neurological injuries. However, the relationship between age-dependent changes in astrocytic Mt function and cognitive decline remains poorly understood. Here, we established that aged astrocytes secret less functional Mt compared to young astrocytes. We found the aging factor C-C motif chemokine 11 (CCL11) is elevated in the hippocampus of aged mice, and that its level is reduced upon systemic administration of young Mt, in vivo. Aged mice receiving young Mt, but not aged Mt improved cognitive function and hippocampal integrity. Using a CCL11-induced aging-like model in vitro, we found that astrocytic Mt protect hippocampal neurons and enhance a regenerative environment through upregulating synaptogenesis-related gene expression and anti-oxidants that were suppressed by CCL11. Moreover, the inhibition of CCL11-specific receptor C-C chemokine receptor 3 (CCR3) boosted the expression of synaptogenesis-related genes in the cultured hippocampal neurons and restored the neurite outgrowth. This study suggests that young astrocytic Mt can preserve cognitive function in the CCL11-mediated aging brain by promoting neuronal survival and neuroplasticity in the hippocampus.
Ryosuke Tashiro, Dan Ozaki, Jesus Bautista-Garrido, Guanghua Sun, Lidiya Obertas, Alexis S Mobley, Gab Seok Kim, Jaroslaw Aronowski, Joo Eun Jung

2243 related Products with: Young Astrocytic Mitochondria Attenuate the Elevated Level of CCL11 in the Aged Mice, Contributing to Cognitive Function Improvement.

11 ml500 Units

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#36733370   2023/01/17 To Up

Distinct phenotype of neutrophil, monocyte, and eosinophil populations indicates altered myelopoiesis in a subset of patients with multiple myeloma.

Hematologic malignancies, including multiple myeloma (MM), promote systemic immune dysregulation resulting in an alteration and increased plasticity of myeloid cell subsets. To determine the heterogeneity of the myeloid cell compartment in the peripheral blood of patients with MM, we performed a detailed investigation of the phenotype and function of myeloid subpopulations. We report that a subset of MM patients exhibits a specific myeloid cell phenotype indicative of altered myelopoiesis characterized by significant changes in the properties of circulating granulocytic, monocytic, and eosinophilic populations. The subset, referred to as MM2, is defined by a markedly elevated level of CD64 (FcγRI) on the surface of circulating neutrophils. Compared to healthy controls or MM1 patients displaying intermediate levels of CD64, neutrophils from MM2 patients exhibit a less differentiated phenotype, low levels of CD10 and CXC chemokine receptor 2 (CXCR2), increased capacity for the production of mitochondrial reactive oxygen species, and an expansion of CD16 immature neutrophil subset. Classical and patrolling monocytes from MM2 patients express elevated levels of CD64 and activation markers. MM2 eosinophils display lower levels of C-C Chemokine receptor 3 (CCR3), Toll-like receptor 4 (TLR4, CD284), and tissue factor (TF, CD142). The MM2 (CD64) phenotype is independent of age, race, sex, and treatment type. Characteristic features of the MM2 (CD64) phenotype are associated with myeloma-defining events including elevated involved/uninvolved immunoglobulin free light chain (FLC) ratio at diagnosis. Detailed characterization of the altered myeloid phenotype in multiple myeloma will likely facilitate the identification of patients with an increased risk of disease progression and open new avenues for the rational design of novel therapeutic approaches.
Krystle L Ong, Marcus D Davis, Kalyn K Purnell, Hannah Cutshall, Harish C Pal, Ashley N Connelly, Christian X Fay, Valeriya Kuznetsova, Elizabeth E Brown, Zdenek Hel

1300 related Products with: Distinct phenotype of neutrophil, monocyte, and eosinophil populations indicates altered myelopoiesis in a subset of patients with multiple myeloma.

16 Arrays/Slide

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#36546900   2022/12/02 To Up

Epitope Mapping of Anti-Mouse CCR3 Monoclonal Antibodies Using Flow Cytometry.

The CC chemokine receptor 3 (CCR3) is a receptor for CC chemokines, including CCL5/RANTES, CCL7/MCP-3, and CCL11/eotaxin. CCR3 is expressed on the surface of eosinophils, basophils, a subset of Th2 lymphocytes, mast cells, and airway epithelial cells. CCR3 and its ligands are involved in airway hyperresponsiveness in allergic asthma, ocular allergies, and cancers. Therefore, CCR3 is an attractive target for those therapies. Previously, anti-mouse CCR3 (mCCR3) monoclonal antibodies (mAbs), CMab-3 (rat IgG, kappa), and CMab-4 (rat IgG, kappa) were developed using the Cell-Based Immunization and Screening (CBIS) method. In this study, the binding epitope of these mAbs was investigated using flow cytometry. A CCR3 extracellular domain-substituted mutant analysis showed that CMab-3, CMab-4, and a commercially available mAb (J073E5) recognized the N-terminal region (amino acids 1-38) of mCCR3. Next, alanine scanning was conducted in the N-terminal region. The results revealed that the Ala2, Phe3, Asn4, and Thr5 of mCCR3 are involved in CMab-3 binding, whereas Ala2, Phe3, and Thr5 are essential to CMab-4 binding, and Ala2 and Phe3 are crucial to J073E5 binding. These results reveal the involvement of the N-terminus of mCCR3 in the recognition of CMab-3, CMab-4, and J073E5.
Nami Tateyama, Teizo Asano, Hiroyuki Suzuki, Guanjie Li, Takeo Yoshikawa, Tomohiro Tanaka, Mika K Kaneko, Yukinari Kato

1708 related Products with: Epitope Mapping of Anti-Mouse CCR3 Monoclonal Antibodies Using Flow Cytometry.

100.00 ug100.00 ug100.00 ug100.00 ug100.00 ug0.5 mg100.00 ug100.00 ug100.00 ug100.00 ug0.1ml (1mg/ml)100.00 ug

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#35804913   2022/06/27 To Up

Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit.

The tumor microenvironment (TME) plays a crucial role in tumor progression. One of its key stromal components, cancer-associated fibroblasts (CAFs), may crosstalk with cancer cells by secreting certain cytokines or chemokines. However, which important mediator(s) are released by CAFs, and the underlying molecular mechanism, remain largely unknown. In the present study, we isolated patient-derived CAFs and normal fibroblasts (NFs). Using microarray analysis, we detected chemokine ligand 11 (CCL11) overexpression in CAFs compared to NFs. CCL11 administration promoted the migration and invasion of head and neck cancer (HNC) cells with enhanced cancer stem cell-like properties and induction of epithelial-to-mesenchymal transition. Furthermore, neutralization of CCL11 activity reversed the aggressive phenotype of CAF-induced cancer cells. Confocal microscopy showed colocalization of CCL11 and CC chemokine receptor 3 (CCR3) on HNC cells. Moreover, immunohistochemical analysis of clinical samples from 104 patients with HNC showed that expression of CCL11 and CCR3 were significantly correlated with poor overall survival ( = 0.003 and 0.044, respectively). Collectively, CCL11 expressed on CAFs promotes HNC invasiveness, and neutralization of CCL11 reverses this effect. We propose that the CCL11/CCR3 signaling circuit is a potential target for optimizing therapeutic strategies against HNC.
Wen-Yen Huang, Yaoh-Shiang Lin, Yu-Chun Lin, Shin Nieh, Yi-Ming Chang, Tsai-Yu Lee, Su-Feng Chen, Kuender D Yang

2785 related Products with: Cancer-Associated Fibroblasts Promote Tumor Aggressiveness in Head and Neck Cancer through Chemokine Ligand 11 and C-C Motif Chemokine Receptor 3 Signaling Circuit.

EachEach

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