Receptors, CXCR4: CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.Receptors, CXCR3: CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11.Receptors, CXCR: Chemokine receptors that are specific for CXC CHEMOKINES.Chemokine CXCL12: A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.Receptors, CXCR5: CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.Receptors, Interleukin-8B: High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and T-LYMPHOCYTES. These receptors also bind several other CXC CHEMOKINES.Chemokines, CXC: Group of chemokines with paired cysteines separated by a different amino acid. CXC chemokines are chemoattractants for neutrophils but not monocytes.Receptors, Interleukin-8A: High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and BASOPHILS.Heterocyclic Compounds: Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)Receptors, Chemokine: 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.Chemokine CXCL11: A CXC chemokine that is induced by GAMMA-INTERFERON. It is a chemotactic factor for activated T-LYMPHOCYTES and has specificity for the CXCR3 RECEPTOR.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Chemokine CXCL10: A CXC chemokine that is induced by GAMMA-INTERFERON and is chemotactic for MONOCYTES and T-LYMPHOCYTES. It has specificity for the CXCR3 RECEPTOR.Chemokine CXCL9: An INTEFERON-inducible CXC chemokine that is specific for the CXCR3 RECEPTOR.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Chemokine CXCL6: A CXC chemokine that has stimulatory and chemotactic activities towards NEUTROPHILS. It has specificity for CXCR1 RECEPTORS and CXCR2 RECEPTORS.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Chemokine CXCL1: A CXC chemokine with specificity for CXCR2 RECEPTORS. It has growth factor activities and is implicated as a oncogenic factor in several tumor types.Chemotaxis, Leukocyte: The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.Chemokine CXCL13: A CXC chemokine that is chemotactic for B-LYMPHOCYTES. It has specificity for CXCR5 RECEPTORS.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Receptors, CCR7: CCR receptors with specificity for CHEMOKINE CCL19 and CHEMOKINE CCL21. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.Cell Line, Tumor: A cell line derived from cultured tumor cells.Mice, Inbred C57BLRNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Receptors, CCR4: CCR receptors with specificity for CHEMOKINE CCL17 and CHEMOKINE CCL22. They are expressed at high levels in T-LYMPHOCYTES; MAST CELLS; DENDRITIC CELLS; and NK CELLS.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Warts: Benign epidermal proliferations or tumors; some are viral in origin.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Receptors, HIV: Cellular receptors that bind the human immunodeficiency virus that causes AIDS. Included are CD4 ANTIGENS, found on T4 lymphocytes, and monocytes/macrophages, which bind to the HIV ENVELOPE PROTEIN GP120.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Receptors, Cytokine: Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Receptors, CCR5: CCR receptors with specificity for CHEMOKINE CCL3; CHEMOKINE CCL4; and CHEMOKINE CCL5. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; MAST CELLS; and NK CELLS. The CCR5 receptor is used by the HUMAN IMMUNODEFICIENCY VIRUS to infect cells.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Kinetics: The rate dynamics in chemical or physical systems.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.HIV Envelope Protein gp120: External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Cell Adhesion: Adherence of cells to surfaces or to other cells.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Mice, Inbred BALB CChemokine CXCL5: A CXC chemokine that is predominantly expressed in EPITHELIAL CELLS. It has specificity for the CXCR2 RECEPTORS and is involved in the recruitment and activation of NEUTROPHILS.Jurkat Cells: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Arrestins: Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Immunodeficiency Virus, Feline: A species of LENTIVIRUS, subgenus feline lentiviruses (LENTIVIRUSES, FELINE) isolated from cats with a chronic wasting syndrome, presumed to be immune deficiency. There are 3 strains: Petaluma (FIP-P), Oma (FIP-O) and Puma lentivirus (PLV). There is no antigenic relationship between FIV and HIV, nor does FIV grow in human T-cells.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Receptors, Scavenger: A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.Lateral Line System: Aquatic vertebrate sensory system in fish and amphibians. It is composed of sense organs (canal organs and pit organs) containing neuromasts (MECHANORECEPTORS) that detect water displacement caused by moving objects.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Receptors, Virus: Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Chemotactic Factors: Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult.Neoplasm Invasiveness: Ability of neoplasms to infiltrate and actively destroy surrounding tissue.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Antigens, CD4: 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Chemokine CXCL2: A CXC chemokine that is synthesized by activated MONOCYTES and NEUTROPHILS. It has specificity for CXCR2 RECEPTORS.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Receptor Cross-Talk: The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Chemokine CCL21: A CC-type chemokine with specificity for CCR7 RECEPTORS. It has activity towards DENDRITIC CELLS and T-LYMPHOCYTES.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Neoplasm Metastasis: The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Oligopeptides: Peptides composed of between two and twelve amino acids.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Receptors, Interleukin: Cell surface proteins that bind interleukins and trigger intracellular changes influencing the behavior of cells.Chemokines, CC: Group of chemokines with adjacent cysteines that are chemoattractants for lymphocytes, monocytes, eosinophils, basophils but not neutrophils.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Bacterial Proteins: Proteins found in any species of bacterium.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Zebrafish Proteins: Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).Mice, Inbred NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Cell SeparationRNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Extracellular Signal-Regulated MAP Kinases: A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.Neovascularization, Physiologic: The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Immunologic Deficiency Syndromes: Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.Breast Neoplasms: Tumors or cancer of the human BREAST.Molecular Weight: The sum of the weight of all the atoms in a molecule.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Antigens, CD34: Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Hematopoietic Stem Cell Mobilization: The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Neovascularization, Pathologic: A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Lymphoid Tissue: Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.HL-60 Cells: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)Mitogen-Activated Protein Kinase 1: A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.

*TP53

... gene encodes proteins that bind to DNA and regulate gene expression to prevent mutations of the genome. In humans, the ... Suppression of p53 in human breast cancer cells is shown to lead to increased CXCR5 chemokine receptor gene expression and ... One such example, human papillomavirus (HPV), encodes a protein, E6, which binds to the p53 protein and inactivates it. This ... In addition to the full-length protein, the human TP53 gene encodes at least 15 protein isoforms, ranging in size from 3.5 to ...

*CCR5

Regions of this protein are also crucial for chemokine ligand binding, functional response of the receptor, and HIV co-receptor ... In humans, the CCR5 gene that encodes the CCR5 protein is located on the short (p) arm at position 21 on chromosome 3. Certain ... During HIV-1 infection, the Gp120 envelope glycoprotein subunit binds to a CD4 glycoprotein and a HIV-1 co-receptor expressed ... Lipp M, Müller G (2003). "Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking". Verhandlungen ...
The chemokine receptors CXCR1-3 bind to 11 chemokines (CXCL1-11) that are clustered on the same chromosome in mammals but are largely missing in ray-finned fish. A second CXCR1/2, and a CXCR3a and CXCR3b gene have been cloned in rainbow trout. Analysis of CXCR1-R3 genes in lobe-finned fish, ray-finned fish and tetrapod genomes revealed that the teleostomian ancestor likely possessed loci containing both OCCR1 and CXCR2, and CXCR3a and CXCR3b. Based on this synteny analysis the first trout CXCR1/2 gene was renamed CXCR1, and the new gene CXCR2. The CXCR1/R2 locus was shown to have further expanded in ray-finned fish. In relation to CXCR3, mammals appear to have lost CXCR3b ...
[45 Pages Report] Check for Discount on C-X-C Chemokine Receptor Type 1 (CDw128a or High Affinity Interleukin 8 Receptor A or IL8 Receptor Type 1 or CD181 or CXCR1) - Pipeline Review, H2 2017 report by Global Markets Direct. According to the recently published report C-X-C Chemokine...
Table of Contents. Table of Contents 2. List of Tables 6. List of Figures 6. Introduction 7. Global Markets Direct Report Coverage 7. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5) Overview 8. Therapeutics Development 9. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by Stage of Development 9. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by Therapy Area 10. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by Indication 11. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Pipeline Products Glance 12. Late Stage Products 12. Early Stage Products 13. C-C Chemokine Receptor Type 5 (C-C CKR-5 or CHEMR13 or HIV-1 Fusion Coreceptor or CD195 or CCR5)-Products under Development by ...
Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokine receptor 3-alternative (CXCR3-alt). CXCR3-A binds to the CXC chemokines CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC) whereas CXCR3-B can also bind to CXCL4 in addition to CXCL9, CXCL10, and CXCL11. CXCR3 is expressed primarily on activated T lymphocytes and NK cells, and some epithelial cells. CXCR3 and CCR5 are preferentially expressed on Th1 cells, whereas Th2 cells favor the expression of CCR3 and CCR4. CXCR3 ligands that attract Th1 cells can concomitantly block the migration of Th2 cells in response to CCR3 ligands, thus enhancing the ...
CXCR4 is the Gi protein-linked seven-transmembrane receptor for the alpha chemokine stromal cell-derived factor 1 (SDF-1), a chemoattractant for lymphocytes. This receptor is highly conserved between human and rodent. CXCR4 is also a coreceptor for entry of human immunodeficiency virus (HIV) in T cells and is expressed in the CNS. To investigate how these CXCR4 ligands influence CNS development and/or function, we have examined the expression and signalling of this chemokine receptor in rat neurons and astrocytes in vitro. CXCR4 transcripts and protein are synthesized by both cell types and in E15 brain neuronal progenitors. In these progenitors, SDF-1, but not gp120 (the HIV glycoprotein), induced activation of extracellular signal regulated kinases (ERKs) 1/2 and a dose-dependent chemotactic response. This chemotaxis was inhibited by Pertussis toxin, which uncouples Gi proteins and the bicyclam AMD3100, a highly selective ...
The major goal of this study was to investigate the effect of severe sepsis on the expression and function of the two CXC chemokine receptors on circulating PMN. We found that CXCR2 expression was reduced by 50% in septic patients, whereas CXCR1 expression was preserved. Similarly, we found that the chemotactic responses to the CXC chemokines which bind with high affinity to only CXCR2 (GRO-α, -β, and -γ and ENA-78) were markedly suppressed in PMN from septic patients, whereas the chemotactic response to IL-8, which binds with high affinity to either CXCR, was preserved. Finally, specific blockade of CXCR1 had a more pronounced suppressive effect on the chemotactic function of PMN from septic patients than on that of PMN from normal donors. Taken together, these observations indicate that CXCR2 is functionally down-regulated in severe sepsis, leaving ...
Platelet-derived SDF-1α (stromal cell derived factor-α) mediates inflammation, immune defence and repair mechanisms at site of tissue injury. This review summarizes the relative expression of CXC chemokine receptor 4 (CXCR4) and CXCR7 in platelets, their dynamic trafficking in presence of ligands like chemokine C-X-C-motif ligand 11 (CXCL11), CXCL12 and MIF (macrophage migration inhibitory factor); how these receptors differentially mediate the functional and survival response to the chemokines CXCL11, CXCL12 and MIF. We further elaborate and emphasize the prognostic significance of platelet surface expression of CXCR4-CXCR7 in the context of coronary artery disease (CAD). SDF-1α/CXCL12, CXCL11, MIF effects mediated through CXCR4 and CXCR7 may play a regulatory role at the site of vascular and tissue inflammation, immune defence and repair where activated platelets reach as forerunners and ...
Laryngeal and hypopharyngeal squamous cell carcinomas (LHSCCs) are common head and neck cancers with a high propensity for lymph node (LN) and lung metastasis. Here, we report that LHSCCs express high levels of functional CXCR4 receptors, native for chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). Primary tumor immunohistochemistry from LHSCC patients has revealed significant expression of CXCR4 and CXCL12. Greater expression of CXCR4 but not that of CXCL12 is correlated with LN and distant metastasis. Reverse transcription-polymerase chain reaction and western blots have demonstrated that CXCR4 messenger RNA (mRNA) and protein were expressed in LHSCC cell lines as well, but failed to detect CXCL12 mRNA expression. CXCL12 treatment enhanced extracellular signal-regulated kinase (ERK) pathway activation and the motility/invasiveness of LHSCC cell lines, which were blocked by treatment with a CXCR4 ...
Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity (By similarity).
The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. This gene, IL8RB, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. [provided by RefSeq, Jul 2008 ...
Oral squamous cell carcinoma (SCC) has a striking tendency to invade to bone. The chemokine stromal cell-derived factor-1 (SDF-1) is constitutively secreted by osteoblasts and plays a key role in homing of hematopoietic cells to the bone marrow. Interleukin (IL)-6 plays an important role in osteoclastogenesis. Herein, we found that SDF-1α increased the secretion of IL-6 in cultured human SCC cells, as shown by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. SDF-1α also increased the surface expression of chemokine receptor 4 (CXCR4) in SCC cells. CXCR4-neutralizing antibody, CXCR4-specific inhibitor (AMD3100) or small interfering RNA against CXCR4 inhibited SDF-1α-induced increase IL-6 production. The transcriptional regulation of IL-6 by SDF-1α was mediated by phosphorylation of extracellular signal-regulated kinases (ERKs) and activation of the nuclear factor-kappa B (NF-κB) ...
Transmembrane signaling of the CXC chemokine stromal cell-derived factor-1 (SDF-1) is mediated by CXCR4, a G protein-coupled receptor initially identified in leukocytes and shown to serve as a coreceptor for the entry of HIV into lymphocytes. Characterization of SDF-1- and CXCR4-deficient mice has revealed that SDF-1 and CXCR4 are of vital developmental importance. To study the role of the SDF-1/CXCR4-chemokine/receptor system as a regulator of vertebrate development, we isolated and characterized a cDNA encoding SDF-1 of the lower vertebrate Xenopus laevis (xSDF-1). Recombinant xSDF-1 was produced in insect cells, purified, and functionally characterized. Although xSDF-1 is only 64-66% identical with its mammalian counterparts, it is indistinguishable from human (h)SDF-1alpha in terms of activating both X. laevis CXCR4 and hCXCR4. Thus, both xSDF-1 and hSDF-1alpha promoted CXCR4-mediated ...
The mild neuroinflammation hypothesis of schizophrenia was introduced by Bechter in 2001.It has been hypothesized that a hypofunction of glutamatergic signaling via N-methyl-n-aspartate receptors (NMDARs) and hyperactivation of dopamine D2 receptors play a role in schizophrenia. The triplet puzzle theory states that sets of triplet amino acid homologies guide two different receptors towards each other and contributes to the formation of a receptor heteromer. It is therefore proposed that putative NMDAR- C-C chemokine receptor type 2 (CCR2), NMDAR- C-X-C chemokine receptor type 4 (CXCR4) and NMDAR- Interleukin 1 receptor type II (IL1R2) heteromers can be formed in the neuronal networks in mild neuroinflammation due to demonstration of Gly-Leu-Leu (GLL), Val-Ser-Thr (VST) and/or Ser-Val-Ser (SVS) amino acid homologies between these receptor protomers. This molecular process may underlie the ability to produce symptoms of schizophrenia in mild ...
CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times. There are currently seven known CXC chemokine receptors in mammals, named CXCR1 through CXCR7. CXCR1 and CXCR2 are closely related receptors that recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif. CXCL8 (otherwise known as interleukin-8) and CXCL6 can both bind CXCR1 in humans, while all other ELR-positive chemokines, such as CXCL1 to CXCL7 bind only CXCR2. They ...
Hematopoietic progenitor cells (HPCs) normally reside in the bone marrow (BM) but can be mobilized into the peripheral blood (PB) after treatment with GCSF or chemotherapy. In previous studies, we showed that granulocyte precursors accumulate in the BM during mobilization induced by either GCSF or cyclophosphamide (CY), leading to the accumulation of active neutrophil proteases in this tissue. We now report that mobilization of HPCs by GCSF coincides in vivo with the cleavage of the N-terminus of the chemokine receptor CXCR4 on HPCs resident in the BM and mobilized into the PB. This cleavage of CXCR4 on mobilized HPCs results in the loss of chemotaxis in response to the CXCR4 ligand, the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). Furthermore, the concentration of SDF-1 decreased in vivo in the BM of mobilized mice, and this decrease coincided with the accumulation of serine proteases able to directly cleave and inactivate SDF-1. Since both SDF-1 ...
Maedi visna virus (MVV) is a retrovirus that is member of the Lentivirus genus. MVV infects sheep and goats and causes progressive pneumonia or paralysis, leading to death. Since the discovery of the receptor for Human immunodeficiency virus (HIV), Simian immunodeficiency virus (SIV) and Feline immunodeficiency virus (FIV) all include the chemokine receptor CXCR4, it has been postulated that all members of the Lentivirus share a common mechanism of entry that involves the use of CXCR4. With the use of syncytia assays, infection-, inhibition- and enhancement studies, it was shown that CXCR4 is not a common lentivirus receptor. U87 and HOS cells, both celllines lacking CXCR4, were susceptible to infection. However, cells transfected with CD4 and CXCR4 showed an increased syncytia formation and the presence of CD¤ and CXCR4 augments virus-induced cell fusion. The nature of MVV receptor is still not known, but ...
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function mutations in chemokine receptor CXCR4. Patient WHIM-09 was spontaneously cured by chromothriptic deletion of 1 copy of 164 genes, including the CXCR4WHIM allele, presumably in a single hematopoietic stem cell (HSC) that repopulated HSCs and the myeloid lineage. Testing the specific contribution of CXCR4 hemizygosity to her cure, we previously demonstrated enhanced engraftment of Cxcr4+/o HSCs after transplantation in WHIM (Cxcr4+/w) model mice, but the potency was not quantitated. We now report graded-dose competitive transplantation experiments using lethally irradiated Cxcr4+/+ recipients in which mixed BM cells containing approximately 5 Cxcr4+/o HSCs and a 100-fold excess of Cxcr4+/w HSCs achieved durable 50% ...
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function mutations in chemokine receptor CXCR4. Patient WHIM-09 was spontaneously cured by chromothriptic deletion of 1 copy of 164 genes, including the CXCR4WHIM allele, presumably in a single hematopoietic stem cell (HSC) that repopulated HSCs and the myeloid lineage. Testing the specific contribution of CXCR4 hemizygosity to her cure, we previously demonstrated enhanced engraftment of Cxcr4+/o HSCs after transplantation in WHIM (Cxcr4+/w) model mice, but the potency was not quantitated. We now report graded-dose competitive transplantation experiments using lethally irradiated Cxcr4+/+ recipients in which mixed BM cells containing approximately 5 Cxcr4+/o HSCs and a 100-fold excess of Cxcr4+/w HSCs achieved durable 50% ...
Abstract. [D-Lys3]-Growth Hormone Releasing Peptide-6 (DLS) is widely utilized in vivo and in vitro as a selective ghrelin receptor (GHS-R) antagonist. Unexpectedly, we identified that DLS also has the ability to block CXCL12 binding and activity through CXCR4 on T cells and peripheral blood mononuclear cells (PBMCs). Moreover, as CXCR4 has been shown to act as a major co-receptor for HIV-1 entry into CD4 positive host cells, we have also found that DLS partially blocks CXCR4-mediated HIV-1 entry and propagation in activated human PBMCs. These data demonstrate that DLS is not the specific and selective antagonist as thought for GHS-R1a and appears to have additional effects on the CXCR4 chemokine receptor. Our findings also suggest that structural analogues that mimic DLS binding properties may also have properties of blocking HIV infectivity, CXCR4 dependent cancer cell migration and ...
Oregon Grape, a popular source of Berberine. SDF-1 binds to a receptor named CXCR-4 (short for C-X-C chemokine receptor type 4. SDF-1 is sometimes referred to as CXCL12, thats where the CXC comes from, but lets try to keep this simple).. Leukemia tumor cells express this CXCR-4 receptor either on their surface or inside the cell. They notice and respond to SDF-1. This cSFD-1/CXCR4 signaling pathway involved in the migration of leukemic cells though the body. A 2008 paper by Li et al reported that because berberine "… could partly inhibit SDF-1 induced AML [acute myeloid leukemia] cells as well as LSCs [leukemic stem cells] migration…… [the authors] hypothesized that berberine could inhibit AML cells migration partly by reducing the secreting of SDF-1 …... Therefore, [they] speculated that berberine might be a potentially effective agent for prevention of leukemia. [1] This hypothesis was based in part by an earlier paper by Tavor et al that ...
TY - JOUR. T1 - CD4-Independent Infection of Astrocytes by Human Immunodeficiency Virus Type 1. T2 - Requirement for the Human Mannose Receptor. AU - Liu, Ying. AU - Liu, Hao. AU - Kim, Byung Oh. AU - Gattone, Vincent H.. AU - Li, Jinliang. AU - Nath, Avindra. AU - Blum, Janice. AU - He, Johnny J.. PY - 2004/4/1. Y1 - 2004/4/1. N2 - Human immunodeficiency virus type 1 (HIV-1) infection occurs in the central nervous system and causes a variety of neurobehavioral and neuropathological disorders. Both microglia, the residential macrophages in the brain, and astrocytes are susceptible to HIV-1 infection. Unlike microglia that express and utilize CD4 and chemokine coreceptors CCR5 and CCR3 for HIV-1 infection, astrocytes fail to express CD4. Astrocytes express several chemokine coreceptors; however, the involvement of these receptors in astrocyte HIV-1 infection appears to be insignificant. In the present study using an expression cloning strategy, the cDNA for ...
Particular populations of stem cells in the bone marrow harbors the membrane receptor CXCR4 which is a specific receptor for chemokine stromal cell-derived factor (SDF-1). In addition, the presence of CXCR4 identifies cells showing expression of early cardiac, muscle and endothelial markers. In mice experiments it was shown that bone marrow contains pools of cells that express early cardiac lineage markers (Nkx2.5/Csx, GATA-4, and MEF2C) and the population can be mobilised by inducing the myocardial infarction. This is the first proof that postnatal bone marrow contains nonhematopoietic population of cells that express markers for cardiac differentiation [4-6]. The peak expression of cardiac markers was found at the same time as most significant increase of stem cells number was measured [12]. A Similar phenomenon seems to occur in humans in the setting of AMI [10]. The SDF-1/CXCR-4 axis seems particularly important in stem/progenitor cell homing, ...
During development, Hedgehog (Hh) signaling controls both cell fate and proliferation, but how cells decide whether to divide or differentiate in response to signaling is not clear. Stückemann et al. report that, in the zebrafish gastrula, Hh signaling promoted proliferation of endoderm and inhibited proliferation of nonendodermal cells (mesoderm and ectoderm). Because the chemokine stromal cell-derived factor 1 (SDF-1) has been implicated in Hh-induced proliferation in other cell types, and because the SDF-1-activated G protein-coupled receptor CXCR4a is present in the endoderm, the authors investigated the role of CXCR4a in the context of early endoderm development. Hh signaling is induced when Hh binds to its transmembrane receptor Patched (Ptc), thus relieving Ptc-mediated repression of the transmembrane protein Smoothened (Smo), which initiates intracellular signal transduction. Knocking down Ptc, therefore, activates Hh signaling. In endodermal cells, ...
The version of the article, "Human Umbilical Vein Endothelial Cells Protect Against Hypoxic-Ischemic Damage in Neonatal Brain via Stromal Cell-derived Factor 1/C-X-C Chemokine Receptor Type 4" by Wu et al that published online ahead-of-print on February 28, 2013, and appears in the May issue (Stroke. 2013;44:1402-1409) contained an error in Ying-Chao Changs affiliation. The correct affiliation is Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. The authors regret the error.. This correction has been made to the online version of the article, which is available at http://stroke.ahajournals.org/content/44/5/1402.. ...
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CXC chemokine ligand 12 (CXCL12), or stromal cell-derived factor 1 (SDF1), is the only known natural ligand for the HIV-1 coreceptor, CXC chemokine receptor 4 (CXCR4). A single nucleotide polymorphism (SNP) in the CXCL12 gene (SDF1-3A) has been associated with disease progression to AIDS in some studies, but not others. Mutations in the CXCR4 gene are generally rare and have not been implicated in HIV-1/AIDS pathogenesis. This study analyzed the SDF1-3A SNP and performed mutation screening for polymorphic markers in the CXCR4 gene to determine the presence or absence of significant associations with susceptibility to HIV-1 infection. The study consisted of 257 HIV-1-seropositive patients and 113 HIV-1-seronegative controls representing a sub-Saharan African population belonging to the Xhosa ethnic group of South Africa. The SDF1-3A SNP was associated with an increased risk ...
The role of SDF-1/CXCR4 in the vasculogenesis and remodeling of cerebral arteriovenous malformation Lingyan Wang,1 Shaolei Guo,2 Nu Zhang,2 Yuqian Tao,3 Heng Zhang,1 Tiewei Qi,2 Feng Liang,2 Zhengsong Huang2 1Department of Neurosurgery ICU, 2Department of Neurosurgery, 3Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China Background: Cerebral arteriovenous malformation (AVM) involves the vasculogenesis of cerebral blood vessels and can cause severe intracranial hemorrhage. Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are believed to exert multiple physiological functions including angiogenesis. Thus, we investigated the role of SDF-1/CXCR4 in the vasculogenesis of cerebral AVM.Methods: Brain AVM lesions from surgical resections were analyzed for the expression of SDF-1, CXCR4, ...
Current combined surgical and neo-adjuvant chemotherapy of primary metastatic osteosarcoma (OS) is ineffective, reflected by a 5-year survival rate of affected patients of less than 20 %. Studies in experimental OS metastasis models pointed to the CXCR4/CXCL12 homing axis as a novel target for OS metastasis-suppressive treatment. The present study investigated for the first time the CXCR4-blocking principle in a spontaneously metastasizing human 143B OS cell line-derived orthotopic xenograft mouse model. The highly metastatic 143B cells, unlike the parental non-metastatic HOS cells, express functional CXCR4 receptors at the cell surface, as revealed in this study by RT/PCR of gene transcripts, by FACS analysis with the monoclonal anti CXCR4 antibody 12G5 (mAb 12G5) and by CXCL12 time- and dose-dependent stimulation of AKT and ERK phosphorylation. A significantly (p , 0.05) higher CXCL12 dose-dependent ...
In the present work, we studied coreceptor usage by 11 primary HIV-2 isolates in U87.CD4 cells expressing chemokine receptors previously shown to function as coreceptors for HIV-1 (CCR1, CCR2b, CCR3, CCR5, and CXCR4) and in GHOST(3) cells expressing CCR5, CXCR4, or orphan receptors implicated in SIV infection (Bonzo and BOB) together with CD4. We found that 10 of 11 primary HIV-2 isolates were able to use CCR5. In contrast, only two isolates, both from patients with advanced disease, were able to efficiently use CXCR4. These two isolates also promptly induced syncytia in MT-2 cells, a pattern described for HIV-1 isolates using CXCR4. However, in contrast to HIV-1 isolates, many of the HIV-2 isolates were promiscuous in their coreceptor usage in that they were able to use, in addition to CCR5, one or more of the CCR1, CCR2b, CCR3, and BOB receptors. This result is in line ...
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 ...
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Everolimus (RAD001, Afinitor) is an mTOR inhibitor FDA-approved for the treatment of patients with advanced clear cell renal cancer (RCC) after failure of treatment with sunitinib or sorafenib, or both drugs. It targets the mammalian target of rapamycin (mTOR) complex inhibiting a serine/threonine kinase regulating PI3K/AKT signaling pathway. Previous evidences demonstrated that the activation of the chemokine receptor CXCR4 involved the mTOR pathway and that CXCR4 was overexpressed in RCC. Recently, also the deorphanized chemokine receptor CXCR7 was described in RCC and defined as an independent prognostic factor. Nevertheless, little is known about the CXCR4-CXCL12-CXCR7-induced signalling. Aim of the study was to investigate if the CXCL12/CXCR4/CXCR7 complex could transduce the signal through mTOR identifying new therapeutic targets. In human renal cancer cells (RXF393, A498) treatment ...
CXCR2 in non-small cell lung cancer (NSCLC) has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. Here, we examined the prognostic importance of CXCR2 in NSCLC and the role of CXCR2 and its ligands in lung cancer cells. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from a murine KRAS/p53-mutant lung adenocarcinoma cell line with high metastatic potential and an orthotopic syngeneic mouse model and in vitro using a CXCR2 small molecule antagonist (SB225002). CXCR2 protein expression was analyzed in tumor cells from 262 NSCLC. Gene expression profiles for CXCR2 and its ligands (CXCR2 axis) were analyzed in 52 human NSCLC cell lines and 442 human lung adenocarcinomas. Methylation of CXCR2 axis promoters was ...
Purpose: : In vivo human and animal studies demonstrate that bone marrow derived endothelial precursor cells (EPCs) play a critical role in neovascularisation and generalized vascular repair. In humans circulating EPCs are being used for therapy to promote vascularisation and correct tissue ischaemia. These bone marrow derived stem cells are recruited to murine choroidal neovascularisation (CNV) and participate in the repair process. The major chemokine for EPC recruitment is SDF. SDFs only known ligand is CXCR4. To better understand the possible involvment of this axis, we investigated the presence and distribution of SDF and CXCR4 in human CNV. Methods: : Sections of 22 surgically excised CNVs were examined by histochemistry and by immunohistochemistry; the latter method employing antibodies to SDF, CXCR4, cytokeratins, CD34 or CD68. The specimens were placed into four aetiological categories, namely; CNV complicating age related macular ...
CXCR4 and CXCL12 have become a major avenue of cancer research since Muller and colleagues established a role for this chemokine receptor/ligand pair in cancer metastasis (22). CXCR4 is upregulated in at least 23 different cancers (3) and is associated with a clinical poor prognosis (23, 24). We reported that CXCR4 activation upregulates β1 integrin function in B16 melanoma cells, enhancing their ability to adhere to the vessel wall, and thereby increasing the risk for lung metastasis (5). Others reported that CXCR4-CXCL12 signaling also promotes lung metastasis through stromal cells (16, 25). For example, CXCR4 recruits myeloid dendritic cells, which enhance tumor growth, angiogenesis, and micrometastasis (25). Mice with CXCR4+/− stromal cells exhibit diminished formation of CXCR4-expressing B16 lung metastasis (16). Administration of AMD3100 to CXCR4+/− ...
Endothelial progenitor cells (EPCs) play an important role in ischemic stroke. However, there are few studies on the relationship between EPC and nondisabling ischemic cerebrovascular events. Our aim was to investigate the association of EPCs and SDF-1 (serum stromal cell-derived factor-1) with NICE (nondisabling ischemic cerebrovascular events). TIA (transient ischemic attack) and minor stroke patients (153 in total) who had an onset of symptoms within 1 day were consecutively collected. 83 of the patients were categorized into the HR-NICE (high-risk nondisabling ischemic cerebrovascular event) group, and 70 of the patients were in the NHR-NICE (non-high-risk nondisabling ischemic cerebrovascular events) group. Adopted FCM (flow cytometry) was used to measure EPCs, taking double-positive CD34/KDR as EPCs. ELISA was used to measure the concentrations of serum SDF-1 and VEGF (vascular endothelial growth factor). By the sequence of admission time, 15 patients were selected separately from the HR-NICE
Although many regenerative cell therapies are being developed to replace or regenerate ischaemic muscle, the lack of vasculature and poor persistence of the therapeutic cells represent major limiting factors to successful tissue restoration. In response to ischaemia, stromal cell-derived factor-1 (SDF-1) is up-regulated by the affected tissue to stimulate stem cell-mediated regenerative responses. Therefore, we encapsulated SDF-1 into alginate microspheres and further incorporated these into an injectable collagen-based matrix in order to improve local delivery. Microsphere-matrix impregnation reduced the time for matrix thermogelation, and also increased the viscosity reached. This double-incorporation prolonged the release of SDF-1, which maintained adhesive and migratory bioactivity, attributed to chemotaxis in response to SDF-1. In vivo, treatment of ischaemic hindlimb muscle with microsphere-matrix led to increased mobilisation of bone marrow-derived ...
Title:Targeting Chemokine (C-X-C motif) Receptor 3 in Thyroid Autoimmunity. VOLUME: 8 ISSUE: 2. Author(s):Poupak Fallahi, Silvia Martina Ferrari, Alda Corrado, Dilia Giuggioli, Clodoveo Ferri and Alessandro Antonelli. Affiliation:Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, I-56126, Pisa, Italy.. Keywords:CXCL9, CXCL10, CXCL11, CXCR3, Graves disease, thyroid autoimmunity, thyroid autoantibodies, thyroiditis.. Abstract:The C-X-C chemokine receptor (CXCR)3 and its chemokines (CXCL9, CXCL10, CXCL11) are involved in the pathogenesis of autoimmune thyroiditis (AT), Graves disease (GD) and Graves Ophthalmopathy (GO). Under the influence of interferon(IFN)γ, the IFNγ-induced protein 10 (IP-10/CXCL10) is secreted by thyrocytes, orbital fibroblasts and preadipocytes. In tissue, Th1 lymphocytes are recruited; hence IFNγ is enhanced, which stimulates CXCL10 secretion reiterating the autoimmune process. The presence of elevated ...
Genetic polymorphisms in chemokine and chemokine receptor genes influence susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and disease progression, but little is known regarding the association between these allelic variations and the ability of the host to transmit virus. In this study, we show that the maternal heterozygous SDF1 genotype (SDF1 3A/wt) is associated with perinatal transmission of HIV-1 (risk ratio [RR], 1.8; 95% confidence interval [CI], 1.0 to 3.3) and particularly postnatal breastmilk transmission (RR, 3.1; 95% CI, 1.1 to 8.6). In contrast, the infant SDF1 genotype had no effect on mother-to-infant transmission. These data suggest that SDF1, which is a ligand for the T-tropic HIV-1 coreceptor CXCR4, may affect the ability of a mother to transmit the virus to her infant. This suggests that a genetic polymorphism in a gene encoding a chemokine receptor ligand may be associated with ...
The angiotensin II type I receptor (AGTR1) has a strong influence on tumor growth, angiogenesis, inflammation and immunity. However, the role of AGTR1 on lymph node metastasis (LNM) in breast cancer, which correlates with tumor progression and patient survival, has not been examined. AGTR1 was highly expressed in lymph node-positive tumor tissues, which was confirmed by the Oncomine database. Next, inhibition of AGTR1 reduced tumor growth and LNM in orthotopic xenografts by bioluminescence imaging (BLI). Losartan, an AGTR1-specific inhibitor, decreased the chemokine pair CXCR4/SDF-1α levels in vivo and inhibited AGTR1-induced cell migration and invasion in vitro. Finally, the molecular mechanism of AGTR1-induced cell migration and LNM was assessed by knocking down AGTR1 in normal cells or CXCR4 in AGTR1high cells. AGTR1-silenced cells treated with losartan showed lower CXCR4 expression. AGTR1 ...
Current treatment modalities for the neurodegenerative disease multiple sclerosis (MS) use disease-modifying immunosuppressive compounds but do not promote repair. Although several potential targets that may induce myelin production have been identified, there has yet to be an approved therapy that promotes remyelination in the damaged central nervous system (CNS). Remyelination of damaged axons requires the generation of new oligodendrocytes from oligodendrocyte progenitor cells (OPCs). Although OPCs are detected in MS lesions, repair of myelin is limited, contributing to progressive clinical deterioration. In the CNS, the chemokine CXCL12 promotes remyelination via CXCR4 activation on OPCs, resulting in their differentiation into myelinating oligodendrocytes. Although the CXCL12 scavenging receptor CXCR7/ACKR3 (CXCR7) is also expressed by OPCs, its role in myelin repair in the adult CNS is unknown. ...
TY - JOUR. T1 - CXCR2 and its related ligands play a novel role in supporting the pluripotency and proliferation of human pluripotent stem cells. AU - Jung, Ji Hye. AU - Lee, Seung Jin. AU - Kim, Jihea. AU - Lee, Songhee. AU - Sung, Hwa Jung. AU - An, Jungsuk. AU - Park, Yong. AU - Kim, Byung Soo. PY - 2015/4/15. Y1 - 2015/4/15. N2 - Basic fibroblast growth factor (bFGF) is a crucial factor sustaining human pluripotent stem cells (hPSCs). We designed this study to search the substitutive factors other than bFGF for the maintenance of hPSCs by using human placenta-derived conditioned medium without exogenous bFGF (hPCCM-), containing chemokine (C-X-C motif) receptor 2 (CXCR2) ligands, including interleukin (IL)-8 and growth-related oncogene α (GROα), which were developed on the basis of our previous studies. First, we confirmed that IL-8 and/or GROα play independent roles to preserve the phenotype of hPSCs. Then, we tried CXCR2 blockage of ...
CXCR4, (a CXC chemokine Receptor), also called fusin, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. This receptor is one of several chemokine receptors that HIV isolates can use to infect CD4+ T cells. Traditionally, HIV isolates that use CXCR4 are known as T-cell tropic isolates. Typically these viruses are found late in infection. It is unclear whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.. CXCR4 is upregulated during the implantation window in natural and Hormone Replacement Therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.. CXCR4s ligand SDF-1 is ...
Dose dependent increases in absolute neutrophil and lymphocyte counts observed in all patients treated with X4P-001-RD. X4P-001-RD was well tolerated and a recommended dose of future Phase 3 study has been established. Interim report from the Phase 2 study presented at the 23rd European Hematology Association Congress CAMBRIDGE, MA - June 15, 2018 - X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 allosteric antagonist drugs to improve immune cell trafficking to treat cancer and rare disease, today announced the presentation of clinical data demonstrating safety and promising activity of X4P-001-RD in patients with WHIM syndrome, a rare primary immunodeficiency disease. The X4P-001-RD clinical data is from the ongoing open-label Phase 2 portion of a Phase 2/3 study in patients with WHIM syndrome, and the presentation was made at the 23rd Congress of the European Hematology Association (EHA) taking place on June 14-17, 2018 in Stockholm, Sweden.. The interim ...
Interactions of human immunodeficiency virus type 1 (HIV-1) with hematopoietic stem cells may define restrictions on immune reconstitution following effective antiretroviral therapy and affect stem cell gene therapy strategies for AIDS. In the present study, we demonstrated mRNA and cell surface expression of HIV-1 receptors CD4 and the chemokine receptors CCR-5 and CXCR-4 in fractionated cells representing multiple stages of hematopoietic development. Chemokine receptor function was documented in subsets of cells by calcium flux in response to a cognate ligand. Productive infection by HIV-1 via these receptors was observed with the notable exception of stem cells, in which case the presence of CD4, CXCR-4, and CCR-5, as documented by single-cell analysis for expression and function, was insufficient for infection. Neither productive infection, transgene expression, nor virus entry was ...
DNA methylation has been implicated in the pathogenesis of chronic pain. However, the specific genes that are regulated by DNA methylation under neuropathic pain condition remain largely unknown. Here we investigated how chemokine receptor CXCR3 is regulated by DNA methylation and its contribution to neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased Cxcr3 mRNA and protein expression in the neurons of spinal cord. Meanwhile, the CpG island in the Cxcr3 gene promoter region was demethylated, and the expression of DNA methyltransferase 3b (DNMT3b) was decreased. SNL also increased the binding of CCAAT/enhancer binding protein α (C/EBPα) with Cxcr3 promoter and decreased the binding of DNMT3b with Cxcr3 promoter in the spinal cord. C/EBPα expression was increased in spinal neurons after SNL, and ...
The results of the present study extend previously published data indicating that the CXCR4 receptor importantly modulates the migratory and angiogenic capacities of cultured human EPC. In line with recent studies indicating that progenitor cell trafficking is regulated by SDF-1,21-23 our data underscore the critical role of CXCR4 for homing of transplanted human EPC into ischemic tissues.. CXCR4 blockade not only resulted in impaired migratory activity toward SDF-1 as well as VEGF but was also associated with an impaired incorporation of EPC into sites of ischemia-induced neovascularization and disturbed restoration of blood flow to ischemic limbs, suggesting that CXCR4 is important for therapeutic integration of EPC into the vascular bed. The role of CXCR4 was supported by experiments using BM-MNC or EPC derived from spleen from heterozygous CXCR4+/− mice. CXCR4+/− cells showed an impaired ...
The ELR+ CXC chemokines play an important role in tumor growth and progression in a number of tumor model systems. IL-8/CXCL8 was the first described angiogenic, mitogenic, and motogenic chemokine in various cancer models and is the prototype of ELR+ CXC chemokines [8, 10-13]. This chemokine was initially discovered on the basis of its ability to induce mobilization of neutrophils and lymphocytes in vivo [9]. Like the basic fibroblast growth factor (bFGF) and the vascular endothelial growth factor (VEGF), it is a strong angiogenesis inducer. IL-8 mediates endothelial cell chemotaxis and proliferation in vitro and in vivo [36].. The fact that all ELR+CXC chemokines mediate angiogenesis highlights the importance of identifying a common receptor that mediates their biological functions in promoting angiogenesis. The candidate CXC chemokine receptors are CXCR1 and CXCR2. Only CXCL-8/IL-8 and CXCL-6 specifically ...
The development of this CXCR4 antibody was featured by Fisher et al. in the article "Reassessment of CXCR4 Chemokine Receptor Expression in Human Normal and Neoplastic Tissues Using the Novel Rabbit Monoclonal Antibody UMB-2" (1). CXCR4 is a CXC chemokine receptor specific for stromal cell-derived factor-1. The protein has 7 transmembrane regions and is located on the cell surface. It acts with the CD4 protein to support HIV entry into cells and is also highly expressed in breast cancer cells. Mutations in CXCR4 have been associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome ...
Mobilized peripheral blood has become the primary source of hematopoietic stem and progenitor cells (HSPCs) for stem cell transplantation, with a 5-day course of granulocyte colony-stimulating factor (G-CSF) as the most common regimen used for HSPC mobilization. The CXCR4 inhibitor plerixafor is a more rapid mobilizer, yet not potent enough when used as a single agent, thus emphasizing the need for faster acting agents with more predictable mobilization responses and fewer side effects. We sought to improve hematopoietic stem cell transplantation by developing a new mobilization strategy in mice through combined targeting of the chemokine receptor CXCR2 and the very late antigen 4 (VLA4) integrin. Rapid and synergistic mobilization of HSPCs along with an enhanced recruitment of true HSCs was achieved when a CXCR2 agonist was coadministered in conjunction with a VLA4 inhibitor. Mechanistic studies revealed involvement of CXCR2 expressed on BM ...
Mobilized peripheral blood has become the primary source of hematopoietic stem and progenitor cells (HSPCs) for stem cell transplantation, with a 5-day course of granulocyte colony-stimulating factor (G-CSF) as the most common regimen used for HSPC mobilization. The CXCR4 inhibitor plerixafor is a more rapid mobilizer, yet not potent enough when used as a single agent, thus emphasizing the need for faster acting agents with more predictable mobilization responses and fewer side effects. We sought to improve hematopoietic stem cell transplantation by developing a new mobilization strategy in mice through combined targeting of the chemokine receptor CXCR2 and the very late antigen 4 (VLA4) integrin. Rapid and synergistic mobilization of HSPCs along with an enhanced recruitment of true HSCs was achieved when a CXCR2 agonist was coadministered in conjunction with a VLA4 inhibitor. Mechanistic studies revealed involvement of CXCR2 expressed on BM ...
Collecting sufficient CD34+ autologous stem cells could enable eligible individuals with specific malignancies to proceed to autologous hematopoietic stem cell transplantation (HSCT). Plerixafor injection is a hematopoietic stem cell mobilizer that is given subcutaneously (SQ) with granulocyte colony stimulating factor (G-CSF). Also known as AMD3100 in early clinical studies, plerixafor injection is the first agent in a class of small molecules that reversibly inhibits the CXCR4 chemokine receptor and blocks binding of the stromal cell-derived factor-1α (SDF-1α). CXCR4 and SDF-1α play a role in the homing of human HSC to the bone marrow (DiPersio, 2009b; Product Information Label, 2013). HSC binding is inhibited with plerixafor injection which releases (mobilizes) CD34+ stem cells from the marrow into the bloodstream where they can be collected through apheresis for subsequent autologous HSCT to treat individuals with multiple myeloma (MM) ...
Regulation of cell migration by changes in oxygen availability is a central event during the organization of host response in inflammatory and neoplastic diseases as it may influence leukocyte recruitment and activation, angiogenesis, and metastasis formation (16). Here, we report that Hyp mediates selective up-regulation of CXCR4 in different cell types, including mononuclear phagocytes (monocytes, MDMs, and TAMs), endothelial cells, and cancer cells, and demonstrate that oxygen levels act as an important regulator of CXCR4 receptor expression. Our data also indicate that HIF-1 activation is involved in the Hyp-dependent up-regulation of CXCR4 expression and that the Hyp-HIF-1-CXCR4 circuit may participate in pathophysiological mechanisms under several conditions, ranging from inflammation to tumor angiogenesis and metastasis.. In contrast to standard cell culture conditions, characterized by 20% oxygen ...
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 ...
GB virus type C (GBV-C) is a common human flavivirus that has been associated with prolonged survival in HIV-positive individuals in several, though not all, epidemiological studies. There are five distinct GBV-C genotypes that are geographically localized, and it has been speculated that GBV-C genotypic differences may explain variable outcomes observed in different clinical studies. Expression of an 85 aa fragment of the GBV-C NS5A phosphoprotein (genotype 2) in a CD4+ T cell line (Jurkat) resulted in inhibition of HIV replication, mediated in part by decreased surface expression of the HIV coreceptor CXCR4 and upregulation of SDF-1. We expressed the NS5A protein from genotypes 1, 2, 3 and 5 in Jurkat cells, and demonstrated that all genotypes inhibited HIV replication. Further deletion mapping demonstrated that expression of a 30 aa fragment resulted in decreased CXCR4 surface expression, upregulation of SDF-1 and inhibition of HIV replication.
Collective migration of cells in the zebrafish Posterior Lateral Line primordium (PLLp) along a path defined by Cxcl12a expression depends on Cxcr4b receptors in leading cells and on Cxcr7b in trailing cells. Cxcr7b-mediated degradation of Cxcl12a by trailing cells generates a local gradient of Cxcl12a that guides PLLp migration. Agent-based computer models were built to explore how a polarized response to Cxcl12a, mediated by Cxcr4b in leading cells and prevented by Cxcr7b in trailing cells, determines unidirectional migration of the PLLp. These chemokine signaling-based models effectively recapitulate many behaviors of the PLLp and provide potential explanations for the characteristic behaviors that emerge when the PLLp is severed by laser to generate leading and trailing fragments. As predicted by our models, the bilateral stretching of the leading fragment is lost when ...
Peritoneal carcinomatosis is a frequent finding in gastric cancer associated with a poor prognosis. The features that enable gastric tumors to disseminate are poorly understood until now. Previously, we showed elevated mRNA levels of phosphoglycerate kinase 1 (PGK1), an ATP-generating enzyme in the glycolytic pathway, the chemokine receptor 4 (CXCR4), the corresponding chemokine ligand 12 (CXCL12) and beta-catenin in specimens from gastric cancer patients with peritoneal carcinomatosis. In this study the influence of PGK1 on CXCR4 and beta-catenin was assessed as well as the invasiveness of PGK1 overexpressing cancer cells. In this current study we found that PGK1 regulates the expression of CXCR4 and beta-catenin at the mRNA and protein levels. On the other hand, CXCR4 regulates the expression of PGK1. Plasmid-mediated overexpression of PGK1 dramatically increased the invasiveness of gastric cancer cells. Interestingly, ...
Chronic lung diseases including asthma and idiopathic pulmonary fibrosis (IPF) are characterized by the airway inflammation, airway remodeling, subepithelial fibrosis, and hypoxia. Previous study indicated that hypoxia plays a critical role in tissue fibrosis. In chronic asthma and IPF, the CXCR4/CXCL12 (stromal cell-derived factor-1, SDF-1) axis plays important role in pulmonary fibrosis. CXCL12 is a potent chemokine for homing of CXCR4+ fibrocytes to sites of lung tissue injury, which directly contribute to pulmonary fibrosis. Circulating CXCR4+ fibrocytes and CXC12 were found to be significantly increases in both plasma and lung of the patient with pulmonary fibrosis. Moreover, an anti-CXCL12 neutralizing antibody attenuated bleomycin-induced pulmonary fibrosis in mice. In addition, CXCL12 plays an important role in carcinoma-associated fibroblast differentiation. These results suggest that interfering with CXCL12 network may help to block pulmonary ...
Author Summary The cellular tropism of HIV-1 is determined by the binding of HIV-1 envelope to chemokine coreceptors, CCR5 or CXCR4, in addition to a major entry receptor, CD4. The mystery still now is that despite the mixed infection of CCR5-utilizing (R5) and CXCR4-utilizing (X4) HIV-1 in many AIDS patients, R5 is predominantly isolated from newly infected individuals whatever the mode of infection. Because the early massive HIV-1 replication occurs in activated T cells and such T-cell activation is induced initially by antigen-presenting DCs, we postulated that the selective expansion of R5 may largely occur at the level of antigen-dependent DC-T cell interaction, called immunological synapse. Thus, the immunological synapse serves as an infectious synapse through which the virus can be rapidly disseminated in vivo. In this study, we prepared X4 and R5 HIV-1 expressing red or green fluorescence and showed that the selective expansion of ...
Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation(要約)Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation(要約) ...
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) ...
Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an intrinsically disordered (unstructured/disordered) protein as it contains regions that do not fold into well-defined protein structures. These disordered regions play important roles in HIVs life cycle, particularly, V3 loop-dependent cell entry, which determines how the virus uses two coreceptors on immune cells, the chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority of infections. Why does this rewiring event occur in HIV-1 infected patients? As changes in the charge of the V3 loop are associated with this receptor switch and it has been suggested that charged residues promote structure disorder, we hypothesise that the intrinsic disorder of the V3 loop is permissive to sequence variation thus contributing to the switch in cell tropism. To test this we use three ...
Caveolin-1 is a protein that is associated with lipid rafts (34, 35). Previous reports in the literature suggest that treatment of cells with DHA and EPA causes a partial displacement of caveolin-1 from the lipid rafts and decreases signaling from molecules such as interleukin-1 in human umbilical cord endothelial cells (24, 25). Our observations confirmed the previous literature and showed that the phenomenon also occurs in MDA-MB-231 breast cancer cells (Fig. 5). A sequence scan of CXCR4 identifies a caveolin-1 consensus binding site (ΦXΦXXXXΦ; YAFLGAKF) at position 310, the interface between the carboxyl tail and the seventh transmembrane domain (36, 37). We observed that treatment of MDA-MB-231 cells resulted in a partial displacement of CXCR4 similar to that of caveolin-1. We suggest a mechanism where CXCR4 binds to caveolin-1 through the consensus binding site. The partial displacement of caveolin-1 ...
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In breast cancer it has been proposed that the presence of cancer stem cells may drive tumor initiation, progression and recurrences. IL-8, up-regulated in breast cancer, and associated with poor prognosis, increases CSC self-renewal in cell line models. It signals via two cell surface receptors, CXCR1 and CXCR2. Recently, the IL-8/CXCR1 axis was proposed as an attractive pathway for the design of specific therapies against breast cancer stem cells. Reparixin, a powerful CXCR1 inhibitor, was effective in reducing in vivo the tumour-initiating population in several NOD/SCID mice breast cancer models, showing that the selective targeting of CXCR1 and the combination of reparixin and docetaxel resulted in a concomitant reduction of the bulk tumour mass and CSC population ...
T lymphocytes, and platelets, as well as cells comprising the fixed macrophage population, including Kupffer cells of the liver, pulmonary alveolar macrophages, osteoclasts, Langerhans cells of the skin, and brain microglial cells. The ability of the hematopoietic stem cell to home to the marrow following intravenous injection is mediated, in part, by an interaction between stromal cell-derived factor 1 (SDF1) produced by marrow stromal cells and the alpha-chemokine receptor CXCR4 found on stem cells. Homing is also influenced by the interaction of cell-surface molecules, termed selectins, on bone marrow endothelial cells with ligands, termed integrins, on early hematopoietic cells. Human hematopoietic stem cells can survive freezing and thawing with little, if any, damage, making it possible to remove and store a portion of the patients own bone marrow for later reinfusion following treatment of the patient with high-dose myelotoxic therapy. ...
CXCL13 is a small chemokine belonging to the CXC chemokine family. As its name suggests, this chemokine is selectively chemotactic for B cells belonging to both the B-1 and B-2 subsets, and elicits its effects by interacting with chemokine receptor CXCR5.[1][3] CXCL13 and its receptor CXCR5 control the organization of B cells within follicles of lymphoid tissues.[4] and is expressed highly in the liver, spleen, lymph nodes, and gut of humans.[1] The gene for CXCL13 is located on human chromosome 4 in a cluster of other CXC chemokines.[2] In T lymphocytes, CXCL13 expression is thought to reflect a germinal center origin of the T cell, particularly a subset of T cells called follicular B helper T cells (or TFH cells). Hence, expression of CXCL13 in T-cell lymphomas, such as Angioimmunoblastic T-cell Lymphoma, is thought to reflect a germinal center origin of the neoplastic T-cells.[5] ...
CXCR3 antibody [CXCR3-173] (chemokine (C-X-C motif) receptor 3) for FACS, Neut. Anti-CXCR3 mAb (GTX14657) is tested in Mouse samples. 100% Ab-Assurance.
The main result of this study is that CXCR3 expression positively modulates ischemia-induced neovascularization, likely through modulation of inflammatory cell infiltration within the ischemic area. This study also extends previous results on the role of MCP-1 in this process and shows a significant impairment in postischemic neovascularization in MCP-1-deficient mice.. Classically, inflammatory cells have been shown to promote neovascularization through various mechanisms, including production of angiogenic factors, secretion of proinflammatory cytokines, and increased matrix degradation.7-9 LPS-induced monocyte accumulation promotes vessel growth, whereas absence of macrophages is associated with a deficient neovascularization response.10,11 A specific role of T cells in this setting was also suggested in Nude mice and in CD4-deficient mice, which exhibit a marked reduction in the angiogenic/arteriogenic process.4,5 In this study, we showed that CXCR3 and its ligands ...
Synonyms for CXCR4 in Free Thesaurus. Antonyms for CXCR4. 34 synonyms for whim: impulse, sudden notion, caprice, fancy, sport, urge, notion, humour, freak, craze, fad, quirk, conceit, vagary, whimsy, passing thought. What are synonyms for CXCR4?
HEK293T-HuCXCR4-FLAG cell line is a hypotriploid human cell line, which has been transfected with a Human chemokine (C-X-C motif) receptor 4 (CXCR4) tagged in the N-terminus with FLAG to allow stably express of the human CXCR4 tagged in the N-terminus with FLAG protein. It is an example of a cell line transfected using our proprietary CBTGS gene screening and amplification system.
Methods and Results-We first localized the membrane-bound form of DPP4 to the capillary endothelia of rat and human heart tissue. Diabetes mellitus promoted the activation of the membrane-bound form of DPP4, leading to reduced myocardial stromal cell-derived factor-1α concentrations and resultant angiogenic impairment in rats. The diabetic rats exhibited diastolic left ventricular dysfunction (DHF) with enhanced interstitial fibrosis caused partly by the increased ratio of matrix metalloproteinase-2 to tissue inhibitor of metalloproteinase-2 in a DPP4-dependent fashion. Both genetic and pharmacological DPP4 suppression reversed the stromal cell-derived factor-1α-dependent microvasculopathy and DHF associated with diabetes mellitus. Pressure overload induced DHF, which was reversed by DPP4 inhibition via a glucagon-like peptide-1/cAMP-dependent mechanism distinct from that for diabetic heart. In patients with DHF, the circulating DPP4 activity in peripheral veins was associated with that in ...
Chemokines orchestrate cell migration for development, immune surveillance, and disease by binding to cell surface heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The array of interactions between the nearly 50 chemokines and their 20 GPCR targets generates an extensive signaling network to which promiscuity and biased agonism add further complexity. The receptor CXCR4 recognizes both monomeric and dimeric forms of the chemokine CXCL12, which is a distinct example of ligand bias in the chemokine family. We demonstrated that a constitutively monomeric CXCL12 variant reproduced the G protein-dependent and β-arrestin-dependent responses that are associated with normal CXCR4 signaling and lead to cell migration. In addition, monomeric CXCL12 made specific contacts with CXCR4 that are not present in the structure of the receptor in complex with a dimeric ...
Les chimiokines sont des petites protéines secrétées dont la fonction principale est la stimulation de la migration de cellules immunitaires vers différents organes et tissus. Elles sont souvent impliquées lors des maladies inflammatoires, auto-immunes et des cancers. Ainsi, les chimiokines et leurs récepteurs couplés aux protéines G (RCPG) sont la cible pharmacologique de plusieurs molécules, actuellement testées en essais cliniques. Nous avons pris comme modèle, lors de notre étude, le récepteur atypique CXCR7. Ce récepteur est dit atypique, car il ne signalise pas via la voie classique des protéines G, mais plutôt via la voie de la β-arrestine. CXCR7 est impliqué dans de nombreux cancers, favorise la progression métastatique et est un co-récepteur pour le virus de limmunodéficience humaine (VIH). Cependant, aucune donnée sur son mode de liaison avec ses ligands CXCL11/ITAC et CXCL12/SDF-1 nexiste à date. Nous pensons que cette information est essentielle pour le ...
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Detection of CXCR4-using human immunodeficiency virus by the Trofile assay was compared to that by assays using virus isolates or replication-competent recombinants. Concordance with the Trofile assay was good, but assays using replicating viruses did not increase substantially the ability to detect the presence of CXCR4-using virus.. ...
Complete information for CXCR5 gene (Protein Coding), C-X-C Motif Chemokine Receptor 5, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
The C-C chemokine receptor type 5 (CCR5) is a key player in HIV infection due to its major involvement in the infection process. Investigations into the role of the CCR5 coreceptor first focused on its binding to the virus and the molecular mechanisms leading to the entry and spread of HIV. The identification of naturally occurring CCR5 mutations has allowed scientists to address the CCR5 molecule as a promising target to prevent or limit HIV infection in vivo. Naturally occurring CCR5-specific antibodies have been found in exposed but uninfected people, and in a subset of HIV seropositive people who show long-term control of the infection. This suggests that natural autoimmunity to the CCR5 coreceptor exists and may play a role in HIV control. Such natural immunity has prompted strategies aimed at achieving anti-HIV humoral responses through CCR5 targeting, which will be described here.
Although there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. Initial interest in pursuing the CXCR4-CXCL12 axis as a target for cancer therapy was fueled by observations implicating CXCR4 in promoting metastasis (2, 28). CXCR4 is expressed in at least 20 different human cancers (8, 29-33); CXCR7 is also expressed in tumors and found to be involved in cell growth, survival, and metastasis (34, 35). Like CXCR4, it is expressed on tumor-associated vessels and on neovasculature (36). On the other hand, CXCL12 is secreted in the tumor microenvironment by stromal cells (21, 28). On the basis of the data such as these, it has been thought that CXCR4 antagonism could prevent the development of metastases by targeting multiple steps in the process of dissemination. Restricted by the tumor type, inhibiting ...
From the Institute of Biomedical Sciences (D.-W.L., M.-L.S.), Department of Chemistry (M.-R.L., C.-Y.C.), Rong Hsing Research Center for Translational Medicine (K.-H.L., W.H.-H.S., M.-L.S.), National Chung Hsing University, Taichung, Taiwan; Department of Ophthalmology (K.-H.L.), Division of Endocrinology and Metabolism (W.H.-H.S.), and Department of Medical Research (W.-J.L., Y.-W.H., M.-L.S.), Taichung Veterans General Hospital, Taiwan; Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan (C.-C.S.); Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (T.-J.C.); Department of Internal Medicine, Armed Forces Taichung General Hospital, Taiwan (T.-J.C.); Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan (S.-H.L.); and Institute of Toxicology, College of Medicine, National Taiwan ...
Drug discovery and early to mid-stage drug development for HIV primarily takes place at academic institutions and small biotechnology companies. At the Frontiers in Developing Antiretroviral Therapy Conference (HIV DART 2014), which took place from December 9-12 in Miami, Florida, there were numerous presentations on promising new treatments for HIV being researched by academic institutions. One project that particularly stood out involved the development of early stage, dual-tropic HIV entry inhibitors that also inhibit HIV reverse transcriptase.. HIV entry into immune cells involves an initial interaction between the viral surface receptor, gp120, and the human cell surface receptor, CD4. This is followed by a subsequent interaction with one of two human cell surface co-receptors: CCR5 or CXCR4. CCR5 is the "entryway" for M-tropic viruses and CXCR4 is the "entryway" for T-tropic viruses. Tropism simply refers to the type of cell that HIV infects, and thus ...
This cohort offers new information about the hematological and infectious profiles of WS. Interestingly, besides the constant neutropenia and lymphopenia, all 8 patients present monocytopenia and half of the patients present profound monocytopenia below 0.1 G/L, contrasting with the monocytosis commonly observed in other congenital neutropenias, such as the elastase neutrophil expressed (ELANE) syndrome. Of particular note, susceptibility to mycobacterial infections may be added to the infection spectrum of WS. Considering the monocytopenia and the infectious profile, composed by pyogenic infections, warts and mycobacteria, WS presents certain similarities with the Mono-MAC syndrome, now identified as the consequence of GATA2 mutations[53, 54]. The major phenotypic difference between the two syndromes is the BM myelokathexis feature the WS.. We previously reported, in leukocytes derived from two patients (UPN 5231 and 5446) from pedigree 4 carrying a mutated CXCR4 receptor, that the ...
C-C chemokine receptor type 5 (CCR5) is utilized by human immunodeficiency virus (HIV) as a co-receptor for cell entry. Suppression of the CCR5 gene by artificial microRNAs (amiRNAs) could confer cell resistance. In previous work, we created a lentivector that encoded the polycistron of two identical amiRNAs that could effectively suppress CCR5. However, tandem repeats in lentiviral vectors led to deletions of the repeated sequences during reverse transcription of the vector RNA. To solve this problem, we have created a new amiRNA against CCR5, mic1002, which has a different microRNA scaffold and targets a different sequence. Replacing one of the two identical tandem amiRNAs in the polycistron with the mic1002 amiRNA increased the accuracy of its lentiviral vector transfer while retaining its ability to effectively suppress CCR5. A lentiviral vector containing two heterogenic amiRNAs significantly inhibited HIV replication in a vector-transduced human CD4+ lymphocyte culture.
Schizophrenia patients typically exhibit cognitive impairments that directly affect their daily functioning, but are not effectively treated by current antipsychotics. Maternal immune activation (MIA) during pregnancy, which can be triggered by a variety of infectious agents, has been associated with the development of schizophrenia in adult offspring. Epidemiological evidence indicates that elevated maternal levels of the chemokine interleukin- 8 (IL-8) during MIA contribute to the neurodevelopmental alterations underlying the disorder. The present experiments used an animal model of neurodevelopmental disorders to study the effects of MIA and chemokine receptor antagonism on the behavior of rat offspring, with behavioral tests chosen to examine cognitive functions that are typically impaired in human schizophrenia patients. The viral mimetic polyinosinic-polycytidylic acid (polyI:C) (4.0 mg/kg, i.v.) was injected into pregnant Long-Evans (LE) dams on gestational day (GD) 15. Dams were also ...
Stem cell transplantation has recently emerged as a promising tool for the treatment of AMI and ADSCs appear to be a suitable candidate for stem cell therapy. However, despite the improved cardiac function and reduced infarct size observed following injection of ADSCs, the clinical benefits and long-term outcomes remain under debate (27-29). The major obstacle in ADSC therapy is the washout of transplanted cells from the heart (30). The magnitude of cell washout may depend on the presence of cell traffcking and/or homing factors in transplanted cells and the heart. The SDF-1α/CXCR4 cascade has previously been identified as a key factor in the recruitment of stem cells to areas of injured tissue in multiple organ systems (31-33), which is fundamental in stem cell therapy following AMI (34). Briefly, on binding to CXCR4, SDF-1α induces the mobilization of calcium, decreases levels of cyclic AMP within the cells and activates several signaling pathways (35). ...
As expected, the soluble CD4 positive control inhibited CXCR4 (50% inhibitory concentration [IC(50)] 3.7 μg/ml) and CCR5 (IC(50) 0.03 μg/ml) tropic HIV-1 infectivity. Free melittin doses ,2 μM were not cytotoxic and were highly effective in reducing HIV-1 infectivity for both CXCR4 and CCR5 strains in TZM-bl reporter cells, while VK2 vaginal cell viability was adversely affected at all free melittin doses tested. However, VK2 cell viability was not affected at any dose of melittin-loaded nanoparticles. Melittin nanoparticles safely and significantly decreased CXCR4 (IC(50) 2.4 μM and IC(90) 6.9 μM) and CCR5 (IC(50) 3.6 μM and IC(90) 11.4 μM) strain infectivity of TZM-bl reporter cells. Furthermore, melittin nanoparticles captured more HIV-1 than blank nanoparticles.. ...
Bipolar disorder (BD) is a common neuropsychiatric disorder characterized by chronic recurrent episodes of depression and mania. Despite evidence for high heritability of BD, little is known about its underlying pathophysiology. To develop new tools for investigating the molecular and cellular basis of BD we applied a family-based paradigm to derive and characterize a set of 12 induced pluripotent stem cell (iPSC) lines from a quartet consisting of two BD-affected brothers and their two unaffected parents. Initially, no significant phenotypic differences were observed between iPSCs derived from the different family members. However, upon directed neural differentiation we observed that CXCR4 (CXC chemokine receptor-4) expressing central nervous system (CNS) neural progenitor cells (NPCs) from both BD patients compared to their unaffected parents exhibited multiple phenotypic differences at the level of neurogenesis and expression of genes critical for ...
Hmc Shantha Kumara, PhD, Hiromichi Miyagaki, MD, Xiaohong Yan, PhD, Myers A Elizabeth, MD, Sonali A C Herath, BS, Joon J Jang, MD, Linda Njoh, MS, Vesna Cekic, RN, Richard L Whelan, MD. Division of Colon and Rectal Surgery, Department of Surgery, St Luke-Roosevelt Hospital Center, Suite 7B, 425 West, 59th Street, New York, NY 10019, USA. Introduction: Minimally invasive colorectal resection (MICR) for cancer results in persistently elevated levels of plasma VEGF, Angiopoietin 2, sVCAM-1, PlGF and other proangiogenic proteins. Plasma from 2nd and 3rd week after MICR stimulates in-vitro endothelial cell (EC) migration, invasion and EC tube formation. The proangiogenic plasma after MICR may stimulate residual cancer growth after surgery. Various cancers (colon, breast, prostate, etc) and endothelial cells (EC) have been shown to express IL8 (CXCR8) and its receptors CXCR1 and CXCR2. Tumor derived IL8, in an autocrine fashion, ...
Disease Markers is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to the identification of disease markers, the elucidation of their role and mechanism, as well as their application in the prognosis, diagnosis and treatment of diseases.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
TY - JOUR. T1 - A critical role for CD63 in HIV replication and infection of macrophages and cell lines. AU - Chen, Hui. AU - Dziuba, Natallia. AU - Friedrich, Brian. AU - Lindern, Jana von. AU - Murray, James L.. AU - Rojo, Daniel R.. AU - Hodge, Thomas W.. AU - OBrien, William A.. AU - Ferguson, Monique. PY - 2008/9/30. Y1 - 2008/9/30. N2 - HIV infection typically involves interaction of Env with CD4 and a chemokine coreceptor, either CCR5 or CXCR4. Other cellular factors supporting HIV replication have also been characterized. We previously demonstrated a role for CD63 in early HIV infection events in macrophages via inhibition by anti-CD63 antibody pretreatment. To confirm the requirement for CD63 in HIV replication, we decreased CD63 expression using CD63-specific short interfering RNAs (siRNA), and showed inhibition of HIV replication in macrophages. Surprisingly, pretreatment with CD63 siRNA not only silenced CD63 expression by 90%, but also inhibited HIV-1 replication in a cultured ...
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
Follicular T helper (Tfh) cells are essential in the formation of high-affinity antibody producing plasma cells and memory B cells. After antigen encounter naive Tfh cells start to upregulate the chemokine receptor CXCR5. This results in homing of the Tfh cells to lymph node follicles where the Tfh cells specifically ... read more localise in germinal centres (GCs). In the GCs the Tfh cells stimulate B cells to differentiate resulting in the production of antibodies. In systemic lupus erythematosus (SLE) an increased amount of autoantibodies is seen. Recent studies postulate that an increased amount of autoantibodies can be related to Tfh cells. The exact role of Tfh cells in the production of autoantibodies in SLE remains elusive, but some research papers provide information from which potential roles can be drawn. The essence of these research papers is the increased level of the chemokine ligand CXCL13 in SLE. CXCL13 levels correlate with disease severity. Further knowledge concerning the ...
Subjects must be able to receive a RTV-boosted PI as part of their OBT regimen. Due to the possibility of randomization to the placebo arm, investigators should consider subjects for enrollment whose treatment history and resistance testing results suggest that an OBT regimen can be constructed which would be anticipated to provide the best possible virological response and clinical benefit for each subject. The drugs in the OBT regimen will be chosen from the locally available antiretrovirals and must consist of between three and six drugs, one of which must be a RTV-boosted PI. Use of investigational PIs which become available through expanded-access or similar programs during the conduct of this study must be authorized by the Sponsor prior to use in OBT regimen ...
Subjects must be able to receive a RTV-boosted PI as part of their OBT regimen. Due to the possibility of randomization to the placebo arm, investigators should consider subjects for enrollment whose treatment history and resistance testing results suggest that an OBT regimen can be constructed which would be anticipated to provide the best possible virological response and clinical benefit for each subject. The drugs in the OBT regimen will be chosen from the locally available antiretrovirals and must consist of between three and six drugs, one of which must be a RTV-boosted PI. Use of investigational PIs which become available through expanded-access or similar programs during the conduct of this study must be authorized by the Sponsor prior to use in OBT regimen ...
Generation of functional hematopoietic stem and progenitor cells (HSPCs) from human pluripotent stem cells (PSCs) has been a long-sought-after goal for use in hematopoietic cell production, disease modeling, and eventually transplantation medicine. Homing of HSPCs from bloodstream to bone marrow (BM) is an important aspect of HSPC biology that has remained unaddressed in efforts to derive functional HSPCs from human PSCs. We have therefore examined the BM homing properties of human induced pluripotent stem cell-derived HSPCs (hiPS-HSPCs). We found that they express molecular effectors of BM extravasation, such as the chemokine receptor CXCR4 and the integrin dimer VLA-4, but lack expression of E-selectin ligands that program HSPC trafficking to BM. To overcome this deficiency, we expressed human fucosyltransferase 6 using modified mRNA. Expression of fucosyltransferase 6 resulted in marked increases in levels of cell surface E-selectin ligands. The glycoengineered cells ...
Invasive mucinous adenocarcinoma (IMA) is a mucinous variant of lepidic predominant lung adenocarcinoma (LPA) and associated with a worse prognosis. We postulated that cytokine expression would enable us to differentiate IMA from LPA in terms of prognosis and acquisition of pro-tumoural capacities. A 30-cytokine panel was assessed in bronchoalveolar lavage fluids (BALF) from IMA (n=38), LPA (n=25) and control samples (n=7). We investigated the expression of differentially expressed cytokines and splice variants of their receptors in surgical samples. The presence of EGFR and KRAS mutations were determined. We also examined the expression of cytokines and splice variants of their receptors in different cell lines, exploring their functional impact on signalling pathways, proliferation and migration. Only C-X-C motif chemokine 10 (CXCL10) was differentially expressed, namely overexpressed in IMA BALF compared with LPA. CXCL10 overexpression in BALF was linked to a worse ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 30 Nov 2017. Apply now!. ...

Burkitt lymphoma receptor 1, GTP-binding protein | definition of Burkitt lymphoma receptor 1, GTP-binding protein by Medical...Burkitt lymphoma receptor 1, GTP-binding protein | definition of Burkitt lymphoma receptor 1, GTP-binding protein by Medical...

What is Burkitt lymphoma receptor 1, GTP-binding protein? Meaning of Burkitt lymphoma receptor 1, GTP-binding protein medical ... GTP-binding protein in the Medical Dictionary? Burkitt lymphoma receptor 1, GTP-binding protein explanation free. ... What does Burkitt lymphoma receptor 1, GTP-binding protein mean? ... Looking for online definition of Burkitt lymphoma receptor 1, ... CXCR5. (redirected from Burkitt lymphoma receptor 1, GTP-binding protein) CXCR5. A gene on chromosome 11q23.3 that encodes a ...
more infohttp://medical-dictionary.thefreedictionary.com/Burkitt+lymphoma+receptor+1%2C+GTP-binding+protein

CXCR5 | Cancer Genetics WebCXCR5 | Cancer Genetics Web

This gene encodes a multi-pass membrane protein that belongs to the CXC chemokine receptor family. It is expressed in mature B- ... This cytokine receptor binds to B-lymphocyte chemoattractant (BLC), and is involved in B-cell migration into B-cell follicles ... Using chromatin immunoprecipitation and reporter gene analysis, we further demonstrated that p65/RelA was able to bind the ... What does this gene/protein do?. Show (8). CXCR5 is implicated in:. - B cell activation - C-X-C chemokine receptor activity - ...
more infohttp://www.cancerindex.org/geneweb/CXCR5.htm

CXCR5 Gene - GeneCards | CXCR5 Protein | CXCR5 AntibodyCXCR5 Gene - GeneCards | CXCR5 Protein | CXCR5 Antibody

Protein Coding), C-X-C Motif Chemokine Receptor 5, including: function, proteins, disorders, pathways, orthologs, and ... Transcription Factor Binding Sites within enhancer. Gene Targets for Enhancer. GH11H118882. 1.5. FANTOM5 Ensembl ENCODE dbSUPER ... Molecular function for CXCR5 Gene. UniProtKB/Swiss-Prot Function: Cytokine receptor that binds to B-lymphocyte chemoattractant ... Summaries for CXCR5 Gene Entrez Gene Summary for CXCR5 Gene. * This gene encodes a multi-pass membrane protein that belongs to ...
more infohttp://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=643

Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B...Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B...

Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine ... Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate ... We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. ... A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly ...
more infohttps://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1201-0

Frontiers | The Transcriptional Regulation of Germinal Center Formation | ImmunologyFrontiers | The Transcriptional Regulation of Germinal Center Formation | Immunology

Regulation of the germinal center gene program by interferon (IFN) regulatory factor 8/IFN consensus sequence-binding protein. ... The dark zone and the light zone of the GC are organized by the expression of the chemokine receptors CXCR4 and CXCR5, ... which is encoded by the Prdm1 gene. By binding to the Prdm1 promoter region, FOXO1 and BCL6 maintain the germinal center DZ ... PAX5 binds to the promoter region of Aicda and activates its expression. Overexpression of PAX5 in a ProB cell line induces the ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2018.02026/full

TP53 - WikipediaTP53 - Wikipedia

TP53 gene encodes proteins that bind to DNA and regulate gene expression to prevent mutations of the genome. In humans, the ... Suppression of p53 in human breast cancer cells is shown to lead to increased CXCR5 chemokine receptor gene expression and ... One such example, human papillomavirus (HPV), encodes a protein, E6, which binds to the p53 protein and inactivates it. This ... In addition to the full-length protein, the human TP53 gene encodes at least 15 protein isoforms, ranging in size from 3.5 to ...
more infohttps://en.wikipedia.org/wiki/TP53

Expression of CXCR5 in cancer - Summary - The Human Protein AtlasExpression of CXCR5 in cancer - Summary - The Human Protein Atlas

The cancer tissue page shows antibody staining of the protein in 20 different cancers. ... Expression of CXCR5 (BLR1, CD185, MDR15) in cancer tissue. ... This gene encodes a multi-pass membrane protein that belongs to ... Burkitt lymphoma receptor 1, GTP binding protein (Chemokine (C-X-C motif) receptor 5); Burkitt lymphoma receptor 1, GTP binding ... This cytokine receptor binds to B-lymphocyte chemoattractant (BLC), and is involved in B-cell migration into B-cell follicles ...
more infohttp://www.proteinatlas.org/ENSG00000160683-CXCR5/pathology

In Vivo Models of Oncoproteins Encoded by Kaposis Sarcoma-Associated Herpesvirus | Journal of VirologyIn Vivo Models of Oncoproteins Encoded by Kaposi's Sarcoma-Associated Herpesvirus | Journal of Virology

Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature 385:347- ... DNA binding and modulation of gene expression by the latency-associated nuclear antigen of Kaposis sarcoma-associated ... functionally homologous to the human interleukin 8 receptor (IL-8R). It binds to the CXC chemokine IL-8 and signals through ... splenocytes from K1 mice display higher levels of IL-6 and CXCR5 mRNAs. At the age of 18 months, 87.5% of K1 mice show signs of ...
more infohttps://jvi.asm.org/content/93/11/e01053-18

STAT3 Targets Suggest Mechanisms of Aggressive Tumorigenesis in Diffuse Large B-Cell Lymphoma | G3: Genes | Genomes | GeneticsSTAT3 Targets Suggest Mechanisms of Aggressive Tumorigenesis in Diffuse Large B-Cell Lymphoma | G3: Genes | Genomes | Genetics

Another notable GCB up-regulated gene is protein kinase C alpha (PKCα), which is encoded by PRKCA (Figure 6B). PKCα is a ... Blue tracks represent gene expression; orange tracks represent STAT3 binding; pink bars show noteworthy STAT3 BRs. CXCR5 shows ... which binds to IL-2 receptors and introduces the diphtheria toxin into cells, killing them (Lansigan et al. 2010). Ontak has ... High STAT3 binding and gene expression in GCB:. A total of 95 genes have greater STAT3 binding and gene expression in GCB cells ...
more infohttp://www.g3journal.org/content/3/12/2173.full

JCI -
Volume 129, Issue 2JCI - Volume 129, Issue 2

... receptor-interacting serine/thronine protein kinase 1 (Rip1), and dynamin-related protein 1 (Drp1). This complex allowed the ... protocol to identify 126 genes of M1 and 116 genes of M28 strains of GAS required for myositis, of which 25% encode ... Finally, SRSF6 binds to the PE, facilitating its inclusion. Moreover, SRSF6 knockdown or CLK inhibition restores WT NEMO ... Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be ...
more infohttps://www.jci.org/129/2

Pathogenesis of COPD (Persistence of Airway Inflammation): Why Does Airway Inflammation Persist After Cessation of Smoking? |...Pathogenesis of COPD (Persistence of Airway Inflammation): Why Does Airway Inflammation Persist After Cessation of Smoking? |...

... the intracellularly located nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene ... Ligand recognition by NOD1 and NOD2 receptors leads to signal transduction through receptor-interacting protein 2 (RIP2) kinase ... In the lungs of smokers with COPD, CD8+ and CD4+ T cells express the tissue-specific chemokine receptors CXCR3, CXCR5, and ... This then leads to the activation of genes encoding different cytokines and chemokines such as IL-8 [23]. Inflammasomes ...
more infohttps://link.springer.com/chapter/10.1007%2F978-981-10-0839-9_4

Protocols and Video Articles Authored by K. Mark Ansel (Translated to Dutch)Protocols and Video Articles Authored by K. Mark Ansel (Translated to Dutch)

Finally, CXCR5(high)CCR7(low) T cells were found to have elevated IL-4 transcript and programmed cell death gene-1 (PD-1) ... Indeed, NFAT1 binds to a consensus binding site found at the mouse cyclin A2 promoter in vitro and in vivo. Luciferase reporter ... Like protein-coding genes, miRNAs can be regulated at the transcriptional level, downstream of signaling pathways and circuits ... We have identified a conserved silencer of the gene encoding interleukin 4 (Il4) marked by DNase I hypersensitivity (HS IV) and ...
more infohttps://www.jove.com/author/K.+Mark_Ansel?language=Dutch

Immune physiologic D/C Flashcards by Lorne  Runge | BrainscapeImmune physiologic D/C Flashcards by Lorne Runge | Brainscape

CXCR5 (CD185) is a 7 transmembrane G protein-coupled receptor for CXCL13. Secreted by T cells. CXCR5 is a follicle homing ... T-bet from gene TBX21, binds to a T-box promoter producing T-bet which stimulates Th1 and NK cells to produce interferon gamma ... S100 proteins are calcium binding proteins with 2 helix loop helix binding sites. Unlike calmodulin they are cell type specific ... MICA (MHC class I polypeptide-related sequence A) encodes a highly polymorphic MHC class I protein that does not associate with ...
more infohttps://www.brainscape.com/flashcards/immune-physiologic-d-c-2484247/packs/4392200

Cell-Based Rna Interference and Related Methods and Compositions - Patent applicationCell-Based Rna Interference and Related Methods and Compositions - Patent application

The target gene may encode a host protein that is co-opted by a virus during viral infection, such as a cell surface receptor ... HIV binds to several cell surface receptors, including CD4 and CXCR5. The introduction of HSCs or other T cell precursors ... gene expression monitoring with a microarray, antibody binding, enzyme linked immunosorbent assay (ELISA), Western blotting, ... 3. The method of claim 2, wherein the target gene encodes a host protein that is co-opted by a virus during viral infection. 4. ...
more infohttp://www.patentsencyclopedia.com/app/20080226553

Skeletal muscle in aged mice reveals extensive transformation of muscle gene expression | BMC Genetics | Full TextSkeletal muscle in aged mice reveals extensive transformation of muscle gene expression | BMC Genetics | Full Text

Specifically, genes associated with energy metabolism, cell proliferation, muscle myosin isoforms, as well as immune functions ... We observed several interesting gene expression changes in the elderly, many of which have not been reported before. Those data ... Further, Smox (spermine oxidase) and GR (glucocorticoid receptor) target Fkbp5 (FK506 binding protein 5), which help to ... In contrast to the down-regulation of the NMJ genes described above, two of the genes encoding the acetylcholine receptor (AChR ...
more infohttps://bmcgenet.biomedcentral.com/articles/10.1186/s12863-018-0660-5

TCF3 | Cancer Genetics WebTCF3 | Cancer Genetics Web

Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also ... protein binding - protein complex - protein dimerization activity - protein heterodimerization activity - protein ... receptor tyrosine kinase-like orphan receptor), a ligand and a receptor from the Wnt signaling pathway, respectively. Although ... YY1 binds to the E3 enhancer and inhibits the expression of the immunoglobulin κ gene via epigenetic modifications.. ...
more infohttp://www.cancerindex.org/geneweb/TCF3.htm

Mono-and dual chemokine/cytokine constructs - Mack, MatthiasMono-and dual chemokine/cytokine constructs - Mack, Matthias

SDF-1 is the ligand, which is capable of binding to the HIV co-receptor CXCR4, used by T-tropic strains of HIV-1. SDF-1 exists ... Optionally, the heterologous sequence can encode a fusion protein including an N-terminal identification peptide imparting ... Specific further co-receptors, in accordance with the present invention comprise, but are not limited to, CXCR3, CXCR4, CXCR5, ... Suitable gene delivery systems may include liposomes, receptor-mediated delivery systems, naked DNA, and viral vectors such as ...
more infohttp://www.freepatentsonline.com/y2006/0078537.html

http://ufdc.ufl.edu/UFE0042955/00001http://ufdc.ufl.edu/UFE0042955/00001

There is a nonmembrane bound singlechained IL22 binding protein (IL22BP) which binds IL 22 with high affinity and multiple ... The IL22 Encoding Gene In humans the IL22 encoding gene is found on the longer arm of chromosome 12, on 12q15, existing as a ... the affinity of IL 22 to its binding protein is approximately 20or 1000fold greater than to its membrane bound receptor, PAGE ... CXCR5+CCR4-CCR6+/ -. Th17 cells are known for secretion of IL17A, IL17F, IL 6, and tumor necrosis factor alpha (TNF4 and IFN ( ...
more infohttp://ufdc.ufl.edu/UFE0042955/00001

T cells in rheumatoid arthritis | Arthritis Research & Therapy | Full TextT cells in rheumatoid arthritis | Arthritis Research & Therapy | Full Text

CXC chemokine receptor (CXCR)4, CXCR5 and CC chemokine receptor (CCR)7 [11]. In this study, Gene Ontology pathway analysis ... A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with ... immunoglobulin binding protein) have also been suggested to be autoantigenic targets [30, 31]. These are ubiquitous proteins ... through the conversion of an epitope with arginine at P4 that binds poorly to HLA-DR4, to an epitope with citrulline with more ...
more infohttps://arthritis-research.biomedcentral.com/articles/10.1186/ar2412

7th meeting of the global arthritis research network | Arthritis Research & Therapy | Full Text7th meeting of the global arthritis research network | Arthritis Research & Therapy | Full Text

The majority of these genes encode proteins that are part of the insulin/TOR signaling pathway. Furthermore, they could show ... NGF binding to its high-affinity receptor tyrosine kinase receptor A (TrkA) in the dorsal root ganglion induces a signal ... a chemokine receptor characteristic of Th-17 cells, are resistant to the induction of EAE. CCR6 binds to its ligand, CCL20, in ... For example, heterodimers of CXCR2/CXCR5 play an important role in cell adhesion. His talk concluded with a model of chemokine ...
more infohttps://arthritis-research.biomedcentral.com/articles/10.1186/ar3340

Signaling pathway Inhibitors - Page 200 - Kinase inhibitor on signaling pathwaySignaling pathway Inhibitors - Page 200 - Kinase inhibitor on signaling pathway

Furthermore we display the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors ... A targeted deletion of exon 3 encoding 65 proteins in the SH2-N site of murine Shp2 (Shp2Δ46-110) leads to embryonic lethality ... We demonstrate that vMIP-II binds to two different receptors CX3CR1 and CCR5 indicated by na?ve CD56Dim CD16Pos NK cells and ... KSHV is normally a professional of immune system evasion and around 25 % from the KSHV encoded genes focus on interfere with ...
more infohttp://achemmic.com/page/200/

B-Cell Lymphoma Medication: Hematopoietic Growth Factors, Monoclonal Antibodies, Corticosteroids, Antineoplastic Agents,...B-Cell Lymphoma Medication: Hematopoietic Growth Factors, Monoclonal Antibodies, Corticosteroids, Antineoplastic Agents,...

Monoclonal antibodies that bind the programmed cell death-1 protein (PD-1) ligands, PD-L1 and PD-L2, to the PD-1 receptor found ... It binds to protein and other compounds containing the SH group. Cytotoxicity can occur at any stage of the cell cycle, but the ... including B cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in trafficking and homing of B ... encoded search term (B-Cell Lymphoma) and B-Cell Lymphoma What to Read Next on Medscape. Related Conditions and Diseases. * ...
more infohttps://emedicine.medscape.com/article/202677-medication

Application # 2018/0251517. NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY
     AGAINST VARIOUS TUMORS -...Application # 2018/0251517. NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST VARIOUS TUMORS -...

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In ... 0116] ESR1 encodes an estrogen receptor, a ligand-activated transcription factor important for hormone binding, DNA binding and ... 0199] Many of the source gene/proteins (also designated "full-length proteins" or "underlying proteins") from which the ... binding assays can be performed. [0263] "Specific" binding means that the scaffold binds the peptide-MHC-complex of interest ...
more infohttp://patents.com/us-20180251517.html

CD antigens / Cluster of DifferentiationCD antigens / Cluster of Differentiation

Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD antibodies are used ... The protein encoded by this gene is a member of the G protein-coupled receptor family.. ... Binds tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing ... CXCR5, BLR1. Homing and cell movement. CD186 antigens. CXCR6, BONZO, STRL33, TYMSTR. B-cell development. ...
more infohttps://www.sinobiological.com/research/cd-antigens/cluster-of-differentiation

Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection | proLékaře.czIntranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection | proLékaře.cz

Článek Serotonin Signaling in : A Serotonin-Activated G Protein-Coupled Receptor Controls Parasite Movement ... Článek Characterisation of a Multi-ligand Binding Chemoreceptor CcmL (Tlp3) of Článek Single Cell Stochastic Regulation of ... β-actin was used to normalize changes in H3 specific gene expression. PCR samples were run and analyzed on a Biorad myIQ RT-PCR ... This was associated with reduced CXCR5 expression on B cells and decreased CXCL13 production within the lung tissue of IL-17-KO ...
more infohttps://www.prolekare.cz/casopisy/plos-pathogens/2014-1/intranasal-vaccination-promotes-detrimental-th17-mediated-immunity-against-influenza-infection-47563
  • In particular, the PreB stage represents the phase during which immunoglobulin (Ig) genes, which code for the antibody molecules, rearrange their DNA segments in order to produce functional genes. (frontiersin.org)
  • Western blots were performed on whole-cell lysate, with equal protein loading in each lane, with the use of anti-STAT3 rabbit polyclonal antibody sc-482X (Santa Cruz Biotechnology, Inc. (g3journal.org)
  • The N-terminus contains two complementary transcriptional activation domains, with a major one at residues 1-42 and a minor one at residues 55-75, specifically involved in the regulation of several pro-apoptotic genes. (wikipedia.org)
  • Among its related pathways are Akt Signaling and Chemokine Superfamily Pathway: Human/Mouse Ligand-Receptor Interactions . (genecards.org)
  • In this section, we discuss the KSHV latent proteins that have been shown to have oncogenic properties in mouse models and the cellular pathways they modulate that potentially explain their roles in tumorigenesis ( Fig. 1 ). (asm.org)
  • KSHV-encoded oncoproteins and their modulation of cancer-inducing pathways leading to tumorigenesis (see reference 1 ) in transgenic mouse models. (asm.org)
  • STAT3 binding sites are present near almost a third of all genes that differ in expression between the two subtypes, and examination of the affected genes identified previously undetected and clinically significant pathways downstream of STAT3 that drive oncogenesis. (g3journal.org)
  • Germline and somatic mosaic mutations in genes encoding components of the PI3K/AKT/mTOR pathway downstream of PTEN predispose to syndromes with partially overlapping clinical features, termed the "PTEN-opathies. (jci.org)
  • KSHV utilizes its proteins to modify the cellular environment to promote viral replication and persistence. (asm.org)
  • Chemokine and chemokine receptors could have played an important role in tumor angiogenesis and distant metastasis. (cancerindex.org)
  • This homolog (originally thought to be, and often spoken of as, a single protein) is crucial in multicellular organisms, where it prevents cancer formation, thus, functions as a tumor suppressor. (wikipedia.org)
  • Hence TP53 is classified as a tumor suppressor gene. (wikipedia.org)
  • In the present study, we sought to further understand the difference in STAT3 function between these two subtypes through mapping its binding regions (BRs) and analyzing gene expression in GCB and ABC patient tumor-derived cell lines. (g3journal.org)
  • Several transgenic mouse models have been developed to study the contributions of KSHV proteins to oncogenesis in vivo . (asm.org)
  • 22. The method of claim 1, wherein the vector is a human ex vivo gene therapy vector. (patentsencyclopedia.com)
  • These signals initiate reciprocal activation and silencing of the interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) cytokine gene loci, changes that are heritably maintained in the resulting T helper type 1 (T(H)1) or T(H)2 cells and their progeny. (jove.com)
  • During latency, a limited number of genes are expressed, and the viral genome is maintained as an episome and is passed to daughter cells during cell division. (asm.org)
  • During lytic infection, most of the viral genes are expressed, the viral genome is replicated, and new virions are produced. (asm.org)
  • Such insights not only teach us about biological mechanisms in states of health and disease, but also enable more accurate gene-informed cancer risk assessment, medical management, and targeted therapeutics. (jci.org)
  • 2. The method of claim 1, wherein the target gene participates in a disease process in the subject. (patentsencyclopedia.com)
  • Neoplastic Cells of Primary Cutaneous CD4+ Small/Medium-sized Pleomorphic T-cell Lymphoma Lack the Expression of Follicular T-helper Cell Defining Chemokine Receptor CXCR5. (cancerindex.org)
  • Immune cell gene expression has been addressed by several studies over the last decade. (biomedcentral.com)
  • What proteins make up the T cell receptor complex? (brainscape.com)
  • 4. The method of claim 3, wherein the host protein is a cell surface receptor for a virus. (patentsencyclopedia.com)
  • This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). (cancerindex.org)
  • t(1;19)(q23;p13.3) TCF3-PBX1 fusion in pre-B-cell ALL t(1;19)(q23;p13.3) translocations fusing the PBX1 and E2A genes occur in approximately a quater of paediatric pre-B cell acute lymphoblastic laeukemias. (cancerindex.org)
  • In this Gem, we focus on animal models of oncogenic KSHV proteins that were developed to enable better understanding of KSHV tumorigenesis. (asm.org)
  • However, it is believed that KSHV proteins play a critical role in tumorigenesis. (asm.org)
  • Expression of KSHV proteins in mice often results in the development of a variety of diseases similar to those linked to KSHV, confirming the contributions of these proteins to KSHV-induced tumorigenesis. (asm.org)
  • These models represent a suitable alternative for the study of KSHV pathogenesis, not only to provide insights into the mechanisms of KSHV-associated tumorigenesis but also to evaluate drugs to treat KSHV-associated infections by targeting these viral proteins. (asm.org)
  • 9aaTADs mediate p53 interaction with general coactivators - TAF9, CBP/p300 (all four domains KIX, TAZ1, TAZ2 and IBiD), GCN5 and PC4, regulatory protein MDM2 and replication protein A (RPA). (wikipedia.org)
  • These genetically modified mice express one or a few KSHV proteins shown to have oncogenic properties in cultured cells. (asm.org)
  • The proliferation of LNCaP cells was also investigated after the knockdown CXCR5. (cancerindex.org)
  • Initially, cigarette smoke influences the expression of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), the intracellularly located nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and receptors for advanced glycation end products (RAGE) on lung epithelial cells, endothelial cells, and leukocytes in the lung. (springer.com)
  • 23. The method of claim 1, further comprising verifying the partial or complete loss of function of the target gene prior to introducing the transfected cells into the subject. (patentsencyclopedia.com)
  • andc) introducing the transfected differentiated cells into the subject,wherein the transfected differentiated cells retain partial to complete loss of function of the target gene. (patentsencyclopedia.com)
  • Interferons that stimulate the INF alpha receptors, R1 and R2 and consist of INF alpha, INF beta, and INF Omega (~20 kd). (brainscape.com)