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.
A CXC chemokine that is chemotactic for B-LYMPHOCYTES. It has specificity for CXCR5 RECEPTORS.
A CXC chemokine that is induced by GAMMA-INTERFERON and is chemotactic for MONOCYTES and T-LYMPHOCYTES. It has specificity for the CXCR3 RECEPTOR.
A CXC chemokine that has stimulatory and chemotactic activities towards NEUTROPHILS. It has specificity for CXCR1 RECEPTORS and CXCR2 RECEPTORS.
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.
A CXC chemokine with specificity for CXCR2 RECEPTORS. It has growth factor activities and is implicated as a oncogenic factor in several tumor types.
An INTEFERON-inducible CXC chemokine that is specific for the CXCR3 RECEPTOR.
Group of chemokines with paired cysteines separated by a different amino acid. CXC chemokines are chemoattractants for neutrophils but not monocytes.
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 receptors that are specific for CXC CHEMOKINES.
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.
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.
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.
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.
A CC-type chemokine that is a chemoattractant for EOSINOPHILS; MONOCYTES; and LYMPHOCYTES. It is a potent and selective eosinophil chemotaxin that is stored in and released from PLATELETS and activated T-LYMPHOCYTES. Chemokine CCL5 is specific for CCR1 RECEPTORS; CCR3 RECEPTORS; and CCR5 RECEPTORS. The acronym RANTES refers to Regulated on Activation, Normal T Expressed and Secreted.
CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.
High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and T-LYMPHOCYTES. These receptors also bind several other CXC CHEMOKINES.
A chemokine that is a chemoattractant for MONOCYTES and may also cause cellular activation of specific functions related to host defense. It is produced by LEUKOCYTES of both monocyte and lymphocyte lineage and by FIBROBLASTS during tissue injury. It has specificity for CCR2 RECEPTORS.
A CXC chemokine that is synthesized by activated MONOCYTES and NEUTROPHILS. It has specificity for CXCR2 RECEPTORS.
A CC-type chemokine with specificity for CCR7 RECEPTORS. It has activity towards DENDRITIC CELLS and T-LYMPHOCYTES.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
A CC chemokine with specificity for CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES and a variety of other immune cells. This chemokine is encoded by multiple genes.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A CC-type chemokine with specificity for CCR4 RECEPTORS. It has activity towards TH2 CELLS and TC2 CELLS.
A CC chemokine with specificity for CCR1 RECEPTORS and CCR5 RECEPTORS. It is a chemoattractant for NK CELLS; MONOCYTES; and a variety of other immune cells. This chemokine is encoded by multiple genes.
A CC-type chemokine that is found at high levels in the THYMUS and has specificity for CCR4 RECEPTORS. It is synthesized by DENDRITIC CELLS; ENDOTHELIAL CELLS; KERATINOCYTES; and FIBROBLASTS.
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.
A CC-type chemokine with specificity for CCR7 RECEPTORS. It has activity towards T LYMPHOCYTES and B LYMPHOCYTES.
A CX3C chemokine that is a transmembrane protein found on the surface of cells. The soluble form of chemokine CX3CL1 can be released from cell surface by proteolysis and act as a chemoattractant that may be involved in the extravasation of leukocytes into inflamed tissues. The membrane form of the protein may also play a role in cell adhesion.
Group of chemokines with adjacent cysteines that are chemoattractants for lymphocytes, monocytes, eosinophils, basophils but not neutrophils.
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.
Ring compounds having atoms other than carbon in their nuclei. (Grant & Hackh's Chemical Dictionary, 5th ed)
The movement of cells or organisms toward or away from a substance in response to its concentration gradient.
A CXC chemokine that is found in the alpha granules of PLATELETS. The protein has a molecular size of 7800 kDa and can occur as a monomer, a dimer or a tetramer depending upon its concentration in solution. Platelet factor 4 has a high affinity for HEPARIN and is often found complexed with GLYCOPROTEINS such as PROTEIN C.
A monocyte chemoattractant protein that has activity towards a broad variety of immune cell types. Chemokine CCL7 has specificity for CCR1 RECEPTORS; CCR2 RECEPTORS; and CCR5 RECEPTORS.
A CC-type chemokine with specificity for CCR6 RECEPTORS. It has activity towards DENDRITIC CELLS; T-LYMPHOCYTES; and B-LYMPHOCYTES.
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.
A CC-type chemokine that is specific for CCR3 RECEPTORS. It is a potent chemoattractant for EOSINOPHILS.
A CC-type chemokine secreted by activated MONOCYTES and T-LYMPHOCYTES. It has specificity for CCR8 RECEPTORS.
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.
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.
A CC-type chemokine with specificity for CCR10 RECEPTORS. It is constitutively expressed in the skin and may play a role in T-CELL trafficking during cutaneous INFLAMMATION.
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.
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.
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.
CCR receptors with specificity for CHEMOKINE CCL2 and several other CCL2-related chemokines. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; MACROPHAGES; BASOPHILS; and NK CELLS.
CCR receptors with specificity for a broad variety of CC CHEMOKINES. They are expressed at high levels in MONOCYTES; tissue MACROPHAGES; NEUTROPHILS; and EOSINOPHILS.
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.
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.
A monocyte chemoattractant protein that attracts MONOCYTES; LYMPHOCYTES; BASOPHILS; and EOSINOPHILS. Chemokine CCL8 has specificity for CCR3 RECEPTORS and CCR5 RECEPTORS.
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.
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.
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.
Heparin-binding proteins that exhibit a number of inflammatory and immunoregulatory activities. Originally identified as secretory products of MACROPHAGES, these chemokines are produced by a variety of cell types including NEUTROPHILS; FIBROBLASTS; and EPITHELIAL CELLS. They likely play a significant role in respiratory tract defenses.
A cell line derived from cultured tumor cells.
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.
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.
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.
High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and BASOPHILS.
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.
CCR receptors with specificity for CHEMOKINE CCL11 and a variety of other CC CHEMOKINES. They are expressed at high levels in T-LYMPHOCYTES; EOSINOPHILS; BASOPHILS; and MAST CELLS.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Adherence of cells to surfaces or to other cells.
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.)
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.
CCR receptors with specificity for CHEMOKINE CCL19 and CHEMOKINE CCL21. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.
Established cell cultures that have the potential to propagate indefinitely.
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.
CCR receptors with specificity for CHEMOKINE CCL27. They may play a specialized role in the cutaneous homing of LYMPHOCYTES.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
CCR receptors with specificity for CHEMOKINE CCL1. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and MACROPHAGES.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
A CC-type chemokine with specificity for CCR3 RECEPTORS. It is a chemoattractant for EOSINOPHILS.
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.
Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells.
Chemokines that are chemoattractants for monocytes. These CC chemokines (cysteines adjacent) number at least three including CHEMOKINE CCL2.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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 receptors that are specific for CC CHEMOKINES.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Group of chemokines with the first two cysteines separated by three amino acids. CX3C chemokines are chemotactic for natural killer cells, monocytes, and activated T-cells.
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.
CCR receptors with specificity for CHEMOKINE CCL20. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
Elements of limited time intervals, contributing to particular results or situations.
Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages.
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.
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.
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)
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.
A blood group consisting mainly of the antigens Fy(a) and Fy(b), determined by allelic genes, the frequency of which varies profoundly in different human groups; amorphic genes are common.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Phenomenon of cell-mediated immunity measured by in vitro inhibition of the migration or phagocytosis of antigen-stimulated LEUKOCYTES or MACROPHAGES. Specific CELL MIGRATION ASSAYS have been developed to estimate levels of migration inhibitory factors, immune reactivity against tumor-associated antigens, and immunosuppressive effects of infectious microorganisms.
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.
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Cytotaxins liberated from normal or invading cells that specifically attract eosinophils; they may be complement fragments, lymphokines, neutrophil products, histamine or other; the best known is the tetrapeptide ECF-A, released mainly by mast cells.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
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.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
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.
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.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
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.
Proteins prepared by recombinant DNA technology.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
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.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
Proteins that specifically inhibit the growth of new blood vessels (ANGIOGENESIS, PHYSIOLOGIC).
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.
Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
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.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
The passage of cells across the layer of ENDOTHELIAL CELLS, i.e., the ENDOTHELIUM; or across the layer of EPITHELIAL CELLS, i.e. the EPITHELIUM.

Chemokine and chemokine receptor gene variants and risk of non-Hodgkin's lymphoma in human immunodeficiency virus-1-infected individuals. (1/2152)

Normal B-lymphocyte maturation and proliferation are regulated by chemotactic cytokines (chemokines), and genetic polymorphisms in chemokines and chemokine receptors modify progression of human immunodeficiency virus-1 (HIV-1) infection. Therefore, 746 HIV-1-infected persons were examined for associations of previously described stromal cell-derived factor 1 (SDF-1) chemokine and CCR5 and CCR2 chemokine receptor gene variants with the risk of B-cell non-Hodgkin's lymphoma (NHL). The SDF1-3'A chemokine variant, which is carried by 37% of whites and 11% of blacks, was associated with approximate doubling of the NHL risk in heterozygotes and roughly a fourfold increase in homozygotes. After a median follow-up of 11.7 years, NHL developed in 6 (19%) of 30 SDF1-3'A/3'A homozygotes and 22 (10%) of 202 SDF1-+/3'A heterozygotes, compared with 24 (5%) of 514 wild-type subjects. The acquired immunodeficiency syndrome (AIDS)-protective chemokine receptor variant CCR5-triangle up32 was highly protective against NHL, whereas the AIDS-protective variant CCR2-64I had no significant effect. Racial differences in SDF1-3'A frequency may contribute to the lower risk of HIV-1-associated NHL in blacks compared with whites. SDF-1 genotyping of HIV-1-infected patients may identify subgroups warranting enhanced monitoring and targeted interventions to reduce the risk of NHL.  (+info)

Identification of CXCR4 domains that support coreceptor and chemokine receptor functions. (2/2152)

The interaction of the chemokine stromal cell-derived factor 1 (SDF-1) with its receptor CXCR4 is vital for cell trafficking during development, is capable of inhibiting human immunodeficiency virus type 1 (HIV-1) utilization of CXCR4 as a coreceptor, and has been implicated in delaying disease progression to AIDS in vivo. Because of the importance of this chemokine-chemokine receptor pair to both development and disease, we investigated the molecular basis of the interaction between CXCR4 and its ligands SDF-1 and HIV-1 envelope. Using CXCR4 chimeras and mutants, we determined that SDF-1 requires the CXCR4 amino terminus for binding and activates downstream signaling pathways by interacting with the second extracellular loop of CXCR4. SDF-1-mediated activation of CXCR4 required the Asp-Arg-Tyr motif in the second intracellular loop of CXCR4, was pertussis toxin sensitive, and did not require the distal C-terminal tail of CXCR4. Several CXCR4 mutants that were not capable of binding SDF-1 or signaling still supported HIV-1 infection, indicating that the ability of CXCR4 to function as a coreceptor is independent of its ability to signal. Direct binding studies using the X4 gp120s HXB, BH8, and MN demonstrated the ability of HIV-1 gp120 to bind directly and specifically to the chemokine receptor CXCR4 in a CD4-dependent manner, using a conformationally complex structure on CXCR4. Several CXCR4 variants that did not support binding of soluble gp120 could still function as viral coreceptors, indicating that detectable binding of monomeric gp120 is not always predictive of coreceptor function.  (+info)

Distinct biological effects of macrophage inflammatory protein-1alpha and stroma-derived factor-1alpha on CD34+ hemopoietic cells. (3/2152)

Chemokines are important regulators of both hemopoietic progenitor cell (HPC) proliferation and adhesion to extracellular matrix molecules. Here, we compared the biological effects of the CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) with those of the CXC chemokine stroma-derived factor-1alpha (SDF-1alpha) on immunomagnetically purified CD34+ cells from leukapheresis products (LP CD34+). In particular, studies on chemokine-induced alterations of LP CD34+ cell attachment to fibronectin-coated plastic surfaces, proliferation of these cells in colony-forming cell (CFC) assays and intracellular calcium mobilization were performed. MIP-1alpha but not SDF-1alpha was found to increase the adhesion of LP CD34+ cells to fibronectin in a dose-dependent manner. Both chemokines elicited growth-suppressive effects on LP CD34+ cells in CFC assays. While MIP-1alpha reduced the number of granulomonocytic (CFC-GM) and erythroid (BFU-E) colonies to the same extent, SDF-1alpha showed a significantly greater inhibitory effect on CFC-GM than BFU-E. Finally, we demonstrated that SDF-1alpha but not MIP-1alpha triggers increases in intracellular calcium in LP CD34+ cells. The SDF-1alpha-induced calcium response was rapid and concentration-dependent, with a maximal stimulation observed at > or = 15 ng/ml. In conclusion, our data suggest distinct biological properties of SDF-1alpha and MIP-1alpha in terms of modulation of LP CD34+ cell adhesion to fibronectin and intracellular calcium levels. However, comparable growth-suppressive effects on HPC proliferation were observed, indicating that this feature may be independent of chemokine-induced calcium responses.  (+info)

Opposite effects of SDF-1 on human immunodeficiency virus type 1 replication. (4/2152)

The alpha-chemokine SDF-1 binds CXCR4, a coreceptor for human immunodeficiency virus type 1 (HIV-1), and inhibits viral entry mediated by this receptor. Since chemokines are potent chemoattractants and activators of leukocytes, we examined whether the stimulation of HIV target cells by SDF-1 affects the replication of virus with different tropisms. We observed that SDF-1 inhibited the entry of X4 strains and increased the infectivity of particles bearing either a CCR5-tropic HIV-1 envelope or a vesicular stomatitis virus G envelope. In contrast to the inhibitory effect of SDF-1 on X4 strains, which is at the level of entry, the stimulatory effect does not involve envelope-receptor interactions or proviral DNA synthesis. Rather, we observed an increased ability of Tat to transactivate the HIV-1 long terminal repeat in the presence of the chemokine. Therefore, the effects of SDF-1 on the HIV-1 life cycle can be multiple and opposite, including both an inhibition of viral entry and a stimulation of proviral gene expression.  (+info)

Shared usage of the chemokine receptor CXCR4 by primary and laboratory-adapted strains of feline immunodeficiency virus. (5/2152)

Strains of the feline immunodeficiency virus (FIV) presently under investigation exhibit distinct patterns of in vitro tropism. In particular, the adaptation of FIV for propagation in Crandell feline kidney (CrFK) cells results in the selection of strains capable of forming syncytia with cell lines of diverse species origin. The infection of CrFK cells by CrFK-adapted strains appears to require the chemokine receptor CXCR4 and is inhibited by its natural ligand, stromal cell-derived factor 1alpha (SDF-1alpha). Here we found that inhibitors of CXCR4-mediated infection by human immunodeficiency virus type I (HIV-1), such as the bicyclam AMD3100 and short peptides derived from the amino-terminal region of SDF-1alpha, also blocked infection of CrFK by FIV. Nevertheless, we observed differences in the ranking order of the peptides as inhibitors of FIV and HIV-1 and showed that such differences are related to the species origin of CXCR4 and not that of the viral envelope. These results suggest that, although the envelope glycoproteins of FIV and HIV-1 are substantially divergent, FIV and HIV-1 interact with CXCR4 in a highly similar manner. We have also addressed the role of CXCR4 in the life cycle of primary isolates of FIV. Various CXCR4 ligands inhibited infection of feline peripheral blood mononuclear cells (PBMC) by primary FIV isolates in a concentration-dependent manner. These ligands also blocked the viral transduction of feline PBMC by pseudotyped viral particles when infection was mediated by the envelope glycoprotein of a primary FIV isolate but not by the G protein of vesicular stomatitis virus, indicating that they act at an envelope-mediated step and presumably at viral entry. These findings strongly suggest that primary and CrFK-adapted strains of FIV, despite disparate in vitro tropisms, share usage of CXCR4.  (+info)

The CC chemokine receptor-7 ligands 6Ckine and macrophage inflammatory protein-3 beta are potent chemoattractants for in vitro- and in vivo-derived dendritic cells. (6/2152)

Dendritic cell migration to secondary lymphoid tissues is critical for Ag presentation to T cells necessary to elicit an immune response. Despite the importance of dendritic cell trafficking in immunity, at present little is understood about the mechanisms that underlie this phenomenon. Using a novel transwell chemotaxis assay system, we demonstrate that the CC chemokine receptor-7 (CCR7) ligands 6Ckine and macrophage inflammatory protein (MIP)-3 beta are selective chemoattractants for MHC class IIhigh B7-2high bone marrow-derived dendritic cells at a potency 1000-fold higher than their known activity on naive T cells. Furthermore, these chemokines stimulate the chemotaxis of freshly isolated lymph node dendritic cells, as well as the egress of skin dendritic cells ex vivo. Because these chemokines are expressed in lymphoid organs and 6Ckine has been localized to high endothelial venules and lymphatic endothelium, we propose that they may play an important role in the homing of dendritic cells to lymphoid tissues.  (+info)

B cell antigen receptor engagement inhibits stromal cell-derived factor (SDF)-1alpha chemotaxis and promotes protein kinase C (PKC)-induced internalization of CXCR4. (7/2152)

The entry of B lymphocytes into secondary lymphoid organs is a critical step in the development of an immune response, providing a site for repertoire shaping, antigen-induced activation and selection. These events are controlled by signals generated through the B cell antigen receptor (BCR) and are associated with changes in the migration properties of B cells in response to chemokine gradients. The chemokine stromal cell-derived factor (SDF)-1alpha is thought to be one of the driving forces during those processes, as it is produced inside secondary lymphoid organs and induces B lymphocyte migration that arrests upon BCR engagement. The signaling pathway that mediates this arrest was genetically dissected using B cells deficient in specific BCR-coupled signaling components. BCR-induced inhibition of SDF-1alpha chemotaxis was dependent on Syk, BLNK, Btk, and phospholipase C (Plc)gamma2 but independent of Ca2+ mobilization, suggesting that the target of BCR stimulation was a protein kinase C (PKC)-dependent substrate. This target was identified as the SDF-1alpha receptor, CXCR4, which undergoes PKC- dependent internalization upon BCR stimulation. Mutation of the internalization motif SSXXIL in the COOH terminus of CXCR4 resulted in B cells that constitutively expressed this receptor upon BCR engagement. These studies suggest that one pathway by which BCR stimulation results in inhibition of SDF-1alpha migration is through PKC-dependent downregulation of CXCR4.  (+info)

Down-regulation of CXCR4 by human herpesvirus 6 (HHV-6) and HHV-7. (8/2152)

Recent studies have demonstrated that human herpesvirus 6 (HHV-6) and HHV-7 interact with HIV-1 and alter the expression of various surface molecules and functions of T lymphocytes. The present study was undertaken to clarify whether coreceptors for HIV-1, CXCR4 and CCR5, are necessary for HHV-6 and HHV-7 infection. Although CXCR4 and CCR5 appeared not to be the coreceptors for these viruses, marked down-regulation of CXCR4, but not CCR5, was detected in HHV-6 variant A (HHV-6A)-, HHV-6 variant B (HHV-6B)-, and HHV-7-infected cells. Down-regulation of CXCR4 resulted in impairment of chemotaxis and a decreased level of elevation of the intracellular Ca2+ concentration in response to stromal cell-derived factor-1. Northern blot analysis of mRNAs extracted from HHV-6A-, HHV-6B-, and HHV-7-infected CD4+ T lymphocytes demonstrated a markedly decreased level of CXCR4 gene transcription, but the posttranscriptional stability of CXCR4 mRNA was not significantly altered. These data demonstrate that unlike HIV-1, HHV-6 and HHV-7 infections do not require expression of CXCR4 or CCR5, whereas marked down-regulation of CXCR4 is induced by these viruses, suggesting that HHV-6 and HHV-7 infections may render CD4+ T lymphocytes resistant to T lymphocyte-tropic HIV-1 infection.  (+info)

Activation of CXCR4 by the CXC chemokine stromal cell-derived factor-1 (SDF-1) requires interaction of the amino-terminal domains of both molecules. We report that proteinases released from either mononucleated blood cells or polymorphonuclear neutrophils degranulated by inflammatory stimuli generate an SDF-1 fragment that is deleted from amino-terminal residues Lys(1)-Pro(2)-Val(3), as characterized by mass spectrometry analysis. The proteolyzed chemokine fails to induce agonistic functions and is unable to prevent the fusogenic capacity of CXCR4-tropic human immunodeficiency viruses. Furthermore, we observed that exposure of CXCR4-expressing cells to leukocyte proteinases results in the proteolysis of the extracellular amino-terminal domain of the receptor, as assessed by flow cytometry analysis and electrophoretic separation of immunoprecipitated CXCR4. Blockade of SDF-1 and CXCR4 proteolysis by the specific leukocyte elastase inhibitor, N-methoxysuccinyl-alanine-alanine-proline-valine-chloromethyl
The chemokine stromal-derived factor-1 (SDF-1) controls many aspects of stem cell function. Details of its regulation and sites of production are currently unknown. We report that in the bone marrow, SDF-1 is produced mainly by immature osteoblasts and endothelial cells. Conditioning with DNA-damagi …
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 activation of heterotrimeric G(i2) in a cell-free system and induced release of intracellular calcium ions ...
Shop Stromal cell-derived factor ELISA Kit, Recombinant Protein and Stromal cell-derived factor Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
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 and its receptor, CXCR4, are ...
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, chemotaxis, engrafment and retention in ...
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, morpholino-mediated knockdown of ...
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 progenitor cells, and also improved ...
Novel Stromal Cell-Derived Factor-1 Polypeptides, Polynucleotides, Modulators Thereof and Methods of Use - diagram, schematic, and image 01 ...
In the adult rodent, stroke induces an increase in endogenous neural progenitor cell (NPC) proliferation in the subventricular zone (SVZ) and neuroblasts migrate towards the ischemic boundary. We investigated the role of stromal cell-derived factor 1alpha (SDF-1alpha) in mediating NPC migration afte …
Polyclonal antibody for GRO alpha/CXCL1 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: WB. Reactive species: Human. GRO alpha/CXCL1 information: Molecular Weight: 11301 MW; Subcellular Localization: Secreted.
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Recombinant Murine Stromal Cell-Derived Factor-1 alpha (rMu SDF-1 alpha) is a recently discovered protein belonging to the alpha-chemokine (C-X-C) family of cytokines. Creative Bioarrays recombinant murine SDF-1 alpha is a 7.9 kDa protein containing 68 amino acid residues ...
Cxcl12 - Cxcl12 (untagged ORF) - Rat chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1) (Cxcl12), transcript variant 3, (10 ug) available for purchase from OriGene - Your Gene Company.
Aiuti, A., Tavian, M., Cipponi, A., Ficara, F., Zappone, E., Hoxie, J., … Bordignon, C. (1999). Expression of CXCR4, the receptor for stromal cell-derived factor-1 on fetal and adult human lympho-hematopoietic progenitors. European Journal of Immunology, 29(6), 1823-1831. https://doi.org/10.1002/(SICI)1521-4141(199906)29:06,1823::AID-IMMU1823,3.0.CO;2- ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
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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 CXCR4 antagonist, as well as by an inhibitor of the MAP kinase pathway. In
[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...
C-X-C Chemokine Receptor Type 2 (CDw128b or GRO/MGSA Receptor or High Affinity Interleukin 8 Receptor B or IL8 Receptor Type 2 or CD182 or CXCR2) - Pipeline Review, ...
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) components p65 and p50. The binding of p65 and p50 to the NF-κB element on ...
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
Dipeptidyl peptidase-4 inhibitors, such as saxagliptin, have been reported to have beneficial effects on β-cell function, but the specific underlying mechanism remains unclear. Stromal cell-derived factor-1α (SDF-1α), a chemokine produced in multiple organs, has been considered as a crucial regulator in promoting β-cell survival. Here, we speculate that SDF-1α might mediate the effect of saxagliptin on improving β-cell function. After 12-week saxagliptin treatment in high-fat diet/streptozotocin-induced diabetic rats, significant improvement in pancreas insulin secretion capacity evaluated by hyperglycemia clamp and increased β-cell to α-cell areas ratio were observed. Saxagliptin significantly induced β-cell proliferation and upregulated the expression of proliferation-related factors including c-myc and cyclind D1 determined with western blotting from the isolated islets. The expression/activity of DPP-4 was significantly reduced and paralleled with the restoration of SDF-1α levels in the
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 ...
Primordial germ cells (PGCs) in the zebrafish embryo face a long migration from the point at which they are specified during development to the location of the future gonad, and it takes some precise signaling to get them there. Major guidance cues are provided by the chemokine SDF-1a (stromal-derived factor-1 alpha), which attracts the PGCs by signaling through its receptor CXCR4b [chemokine (C-X-C motif) receptor 4b]. SDF-1a also binds to another receptor, CXCR7, but the function of this receptor in PGC cell migration has been uncertain. Boldajipour et al.s experiments indicate that CXCR7s function is not to signal but rather to act as a sink that soaks up stray molecules of SDF-1a, thus adding to the precision of SDF-1a signaling through CXCR4b. Transplantation experiments taking PGCs from animals lacking CXCR7 into wild-type embryos showed that the critical function of CXCR7 was in somatic cells, not the PGCs. Microscopy of fluorescently tagged proteins showed that CXCR7 promoted ...
Clone REA649 recognizes the human CD184 antigen, a multi-pass membrane protein, also known as C-X-C chemokine receptor type 4 (CXCR4), leukocyte-derived seven transmembrane domain receptor (LESTR), or fusin. CD184 is ubiquitously expressed on blood and tissue cells. It mediates chemotaxis in mature and progenitor blood cells and is important for B lymphopoiesis, myelopoiesis, and cardiogenesis. CD184 exclusively interacts with the endogenous ligand CXCL12. Binding of CXCL12 transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Although CXCL12 is the only known chemokine that binds CD184, recent studies suggest that extracellular ubiquitin also acts as an immune modulator through CD184-mediated signaling. CD184 is a coreceptor for HIV entry by promoting Env-mediated fusion of the virus.Additional information: Clone REA649 displays negligible binding to Fc receptors. | Ísland
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This gene encodes 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
Stromal cell-derived factor-1 beta (SDF-1 β), also called CXCL12b, is one of two SDF-1 splice variants made by a wide variety of cells upon stimulation by inflammatory cytokines such as TNF, IL-1, and LPS. SDF-1 β signals through the G protein-coupled receptor CXCR4 to recruit activated leukocytes.
Results Mean age was 48.28±3.88 for controls and 49.48±9.88 for patients (p=0.19); 53 controls (95%) and 97 patients (97%) were women (p=0.23). Diastolic dysfunction was present in 1 control (1.7%) and 61 SSc patients (61%) (p=0.0003). NT-proBNP levels were 22.24 pg/ml ±8.48 for controls, 50.51 pg/ml (12-253) for patients without DD and 336.15 pg/ml (17-2250) for patients with DD (p=0.0001). CD309/34+ EPC was 0.84 cels/ml (0.1-3.1) for controls, 1.71 cels/ml (0.1-5.5) for patients without DD and 0.86 cels/ml (0.01-5.5) for patients with DD (p=0.0001); same tendency was observed with other two subtypes of EPC. Subanalysis showed that EPC was different (p=0.0001) among mild, moderate and severe DD. ...
MacArthur, John W. et al Sustained Release of Engineered Stromal Cell-Derived Factor 1-α From Injectable Hydrogels Effectively Recruits Endothelial Progenitor Cells and Preserves Ventricular Function After Myocardial Infarction. Circulation 128.11 suppl 1 (2013): S79-S86. Web. 22 Jan. 2018. ...
Sustained release of engineered stromal cell-derived factor 1-a from injectable hydrogels effectively recruits endothelial progenitor cells and preserves vent
Sel punca kanker inggih punika sèl ingkang ngaktivasi lintasan onkogenik wujud tumorigenesis ingkang damel sèl normal nglampahi fase inisiasi tumor, nanging sèl pucuk kanker boten gadhah sipat namun tumorigenik.[7] saking data pungkasan, dipuntemuake selpuncak kanker ing pinten-pinten jinis kanker seperti leukimia, kanker payudara, kanker utek, kanker utek, kanker usus besar dan kanker kulit. Sel punca kanker pankreas gadhah kluster diferensiasi CD44, CD24 saha epithelial-specific antigen, selain SDF-1 (stromal cell-derived factor 1)/CXCR4 kanggé migrasi kados ta sèl punca normal,[8] sarta èksprèsi genetiklangkung inggal saking lebih tinggi ari sèl punca normal, kados ta gen BMI-1 dan SHH (Sonic hedgehog) kanggé nguwali piyambakipun,,[9] ...
C-X-C Motif Chemokine 2/CXCL2/MIP-2 product information; C-X-C Motif Chemokine 2/CXCL2/MIP-2 is available 1 time from supplier EnoGene at Gentaur.com shop
CD184, also known as CXCR4 or fusin, is a receptor for the C-X-C chemokine SDF-1. It is expressed mainly in hematopoietic cells, vascular endothelium, and neural tissue. CD184 is a G-protein coupled receptor containing extracellular N-terminal, seven transmembrane domains and intracellular C-terminal domain. It transduces signal by increasing the intracellular calcium level. CD184 plays an essential role in vascularization of the gastrointestinal tract, and is involved in cerebellar development and in hematopoiesis. It is also a coreceptor (with CD4) for HIV-1 X4 virus and a primary receptor for some HIV-2 isolates ...
CXCL12 izaziva potentnu hemotaksu limfocita.[4][5][6][7] Tokom embriogeneze on usmerava migraciju hematopoetskih ćelija i formiranje velikih krvnih sudova. Miševi bez CXCL12 gena su letalni pre rođenja, ili u toku prvog sata života. Kod odraslih CXCL12 igra važnu ulogu u angiogenezi putem regrutovanja endotelnih progenitorskih ćelija (EPC) iz koštane srži kroz CXCR4 zavistan mehanizam.[8] Ova funkcija čini CXCL12 veoma važnim faktorom u karcinogenezi i neovaskularizaciji vezanoj za progresiju tumora.[9] CXCL12 takođe ima ulogu u metastazi tumora gde su ćelije raka koje izražavaju CXCR4 receptor privučene ka metastaznim ciljnim tkivima koja oslobađaju ligand, CXCL12.[10] Kod raka dojke, međutim, povećano CXCL12 izražavanje određuje umanjeni rizik od metastaze.[11][12] ...
The experiments described in this study suggest that the chemokine SDF-1 acts as a neurotransmitter in the DG. The evidence supporting this supposition is similar to that available for GABA, certainly a well-established neurotransmitter. Thus, both GABA and SDF-1 are localized in synaptic vesicles within DG nerve terminals. Both GABA and SDF-1 produce similar electrophysiological effects on nestin-EGFP and DCX-EGFP-expressing cells in the SGZ. Moreover, it appears that both GABA and SDF-1 are tonically released in the DG. Thus, addition of both GABAA and CXCR4 receptor blockers elicited an outward current, suggesting that GABA and SDF-1 normally exert a tonic influence on type 2 progenitor cells. It also appears that the effects of GABA and SDF-1 are linked in some way because the observed effects of SDF-1 are sensitive to both GABAA and CXCR4 blockers.. SDF-1 and its receptor CXCR4 have been shown to be widely expressed throughout the developing and adult nervous systems (Stumm et al., 2002; ...
This antimicrobial gene encodes a chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. This gene may also be a key regulator of the cytokine storm immune response to SARS-CoV-2 infection. [provided by RefSeq, Sep 2020 ...
Complete information for CXCL9 gene (Protein Coding), C-X-C Motif Chemokine Ligand 9, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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Aortic and plasma expression levels of IL-18 and CXCL16.(A) Reduced aortic mRNA expression of IL-18 and CXCL16, but no change in the expression of IFN-γ is obs
The aim of the present study was to characterize the defect in chemokine-induced αLβ2 activation that we have previously identified in α4β1+ CLL cells ( 3, 4).. Because many CLL clones express little or no α4β1 ( 3, 5), we started the present studies by examining chemokine-induced αLβ2 clustering on these cells. The αL of α4− CLL cells also failed to undergo polar clustering or αLβ2-dependent motility when incubated on ligand in the presence of chemokine. Because the αLβ2 of normal B cells becomes clustered under these conditions ( 4), this indicates that defective αL clustering in response to chemokine is a feature of CLL cells, regardless of their expression of α4β1.. We next found that the αLβ2 of CLL cells tested directly ex vivo is in an activated conformation, but the degree of activation varied among cases, with α4− clones expressing the high-affinity, fully activated form of αLβ2; furthermore, these cells were able to bind ICAM-1. In contrast, α4β1+ cells ...
TY - JOUR. T1 - The role of metabotropic glutamate receptor 5 on the stromal cell-derived factor-1/CXCR4 system in oral. AU - Kuribayashi, Nobuyuki. AU - Uchida, Daisuke. AU - Kinouchi, Makoto. AU - Takamaru, Natsumi. AU - Tamatani, Tetsuya. AU - Nagai, Hirokazu. AU - Miyamoto, Youji. PY - 2013/11/13. Y1 - 2013/11/13. N2 - We have demonstrated that blocking CXCR4 may be a potent anti-metastatic therapy for CXCR4-related oral cancer. However, as CXCR4 antagonists are currently in clinical use to induce the mobilization of hematopoietic stem cells, continuous administration as an inhibitor for the metastasis may lead to persistent leukocytosis. In this study, we investigated the novel therapeutic downstream target(s) of the SDF-1/CXCR4 system, using B88-SDF-1 cells, which have an autocrine SDF-1/CXCR4 system and exhibit distant metastatic potential in vivo. Microarray analysis revealed that 418 genes were upregulated in B88-SDF-1 cells. We identified a gene that is highly upregulated in B88-SDF-1 ...
Hypoxia is known to regulate the expression of genes involved in the migration of various cell types. Although many studies have shown that hypoxia increases cell migration, it still remains unclear whether hypoxia could modulate the stromal cell derived factor-1 (SDF-1)-dependent migration of leukemic cell. Herein, we demonstrated that the SDF-1-dependent migration of HL-60, was reduced under hypoxia with no comparable decrease of CXC-type chemokine receptor CXCR4, a cognate receptor for SDF-1. Furthermore, we showed that migration toward SDF-1 was reduced by inactivation of either serine/threonine kinase Akt or extracellular signal regulated kinase Erk, which was confirmed by selective pathway inhibitor LY294002 and PD98059. In our results, phosphorylation of Erk was increased under hypoxia, but phosphorylation of Akt was attenuated on the contrary. These results led us to conclusion that hypoxia could inhibit the SDF-1-dependent migration of HL-60 via blocking of Akt activation ...
Chemokines mediate diverse fundamental biological processes, including combating infection. Multiple chemokines are expressed at the site of infection; thus chemokine synergy by heterodimer formation may play a role in determining function. Chemokine function involves interactions with G-protein-coupled receptors and sulfated glycosaminoglycans (GAG). However, very little is known regarding heterodimer structural features and receptor and GAG interactions. Solution nuclear magnetic resonance (NMR) and molecular dynamics characterization of platelet-derived chemokine CXCL7 heterodimerization with chemokines CXCL1, CXCL4, and CXCL8 indicated that packing interactions promote CXCL7-CXCL1 and CXCL7-CXCL4 heterodimers, and electrostatic repulsive interactions disfavor the CXCL7-CXCL8 heterodimer. As characterizing the native heterodimer is challenging due to interference from monomers and homodimers, we engineered a
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 looked at the role of CXCR4 in the ...
Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) prime endothelial cells to respond to hematopoietic chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. Coculture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the hematopoietic chemokine CXCL12 and its CXCR4 receptor by day 3 of coculture. Chronic exposure to the CXCR4 antagonist AMD3100 in this vasculo/angiogenesis assay significantly reduced vascular tubule formation, an observation recapitulated by delayed AMD3100 addition. While AMD3100 did not affect ECFC-derived cell proliferation, it did demonstrate a dual action. First, over the later stages of the 14-day cocultures, AMD3100 delayed tubule organization into maturing vessel networks, resulting in enhanced endothelial cell retraction and loss of complexity as defined by
Although ovarian cancer is rare, it is the most deadly of gynaecological cancers. Unfortunately, still very little is known about the cells that give rise to 90% of ovarian cancers, the ovarian surface epithelial (OSE) cells, and much of the available data remains controversial. This project was designed to address the possible involvement of ovarian stromal/thecal cells in the regulation of OSE cell growth and Kit and KL expression. Such interactions are probably involved in normal OSE-stromal/thecal cell activities as well as in interactions occurring within inclusion cysts and leading to ovarian tumour formation. The regulation of rat OSE (ROSE) cell growth by theca-derived factors and gonadotropins was investigated by proliferation experiments and cell counts. The modulation of Kit and Kit ligand (KL) messenger ribonucleic acid (mRNA) expression in these cells by the same factors was investigated by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). ...
Background: Metastasis, the spread and growth of tumor cells to distant organ sites, represents the most devastating attribute and plays a major role in the morbidity and mortality of cancer. Inflammation is crucial for malignant tumor transformation and survival. Thus, blocking inflammation is expected to serve as an effective cancer treatment. Among anti-inflammation therapies, chemokine modulation is now beginning to emerge from the pipeline. CXC chemokine receptor-4 (CXCR4) and its ligand stromal cell-derived factor-1 (CXCL12) interaction and the resulting cell signaling cascade have emerged as highly relevant targets since they play pleiotropic roles in metastatic progression. The unique function of CXCR4 is to promote the homing of tumor cells to their microenvironment at the distant organ sites. Methodology/Principal Findings: We describe the actions of N,N-(1,4-phenylenebis(methylene))dipyrimidin-2-amine (designated MSX-122), a novel small molecule and partial CXCR4 antagonist with ...
Cxcl12 - Cxcl12 (Myc-DDK-tagged ORF) - Rat chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1) (Cxcl12), transcript variant 2, (10 ug) available for purchase from OriGene - Your Gene Company.
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Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenviroment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system ...
Beyond the influences of other cytokines on EPO effects, new and surprising information on EPO should also be taken into consideration. For example, the enzyme DPP4 (CD26), which is present on the surface of many cell types and in soluble form in the circulation, truncates chemokines such as stromal cell-derived factor-1 (SDF-1/CXCL12), and changes their biological activity (Christopherson et al., 2002, 2004). DPP4 has similar effects on several CSFs, including EPO, truncating the protein at the N terminus-penultimate alanine or proline. Unlike full-length SDF-1, DPP4-truncated SDF-1 is inactive as a chemotactic molecule and survival factor in vitro (Christopherson et al., 2002; Broxmeyer et al., 2012) and as a homing molecule in vivo (Christopherson et al., 2004), and can block the activity of full-length SDF-1. These effects are counteracted by inhibition of DPP4 by specific peptides (Diprotin A [ILE-PRO-ILE] or Val-Pyr) or a small molecule (sitagliptin). Similarly, DPP4 truncates EPO into a ...
In this study, we show that the chemokine SDF-1 and its cognate receptor CXCR4 are expressed in breast cancer in vivo and analyze the effects of manipulating these proteins in a coculture model of mammary carcinoma and vascular endothelial cells. The evidence presented suggests that activation of the SDF-1/CXCR4 axis in a growing tumor contributes to angiogenesis and the initial steps of metastasis. CXCR4 activation had surprisingly similar effects on tumor and endothelial cells: it induced proliferation and migration. In addition, SDF-1 binding to CXCR4 led to specific effects on endothelial and tumor cells: in endothelial cells, CXCR4 stimulated tube formation which may point to proangiogenic activity in vivo, whereas in the tumor cells activation of this receptor resulted in adhesion to endothelial cells and transendothelial migration.. In addition to their hematopoietic activities, SDF-1 and CXCR4 have been implicated in the regulation of angiogenesis in a number of (patho)physiological ...
CXCL12 izaziva potentnu hemotaksu limfocita.[4][5][6][7] Tokom embriogeneze on usmerava migraciju hematopoetskih ćelija i formiranje velikih krvnih sudova. Miševi bez CXCL12 gena su letalni pre rođenja, ili u toku prvog sata života. Kod odraslih CXCL12 igra važnu ulogu u angiogenezi putem regrutovanja endotelnih progenitorskih ćelija (EPC) iz koštane srži kroz CXCR4 zavistan mehanizam.[8] Ova funkcija čini CXCL12 veoma važnim faktorom u karcinogenezi i neovaskularizaciji vezanoj za progresiju tumora.[9] CXCL12 takođe ima ulogu u metastazi tumora gde su ćelije raka koje izražavaju CXCR4 receptor privučene ka metastaznim ciljnim tkivima koja oslobađaju ligand, CXCL12.[10] Kod raka dojke, međutim, povećano CXCL12 izražavanje određuje umanjeni rizik od metastaze.[11][12] ...
Therapies based on circulating proangiogenic cells (PACs) have shown promise in ischemic disease models but require further optimization to reach the bedside. Ischemia-associated hypoxia robustly increases microRNA-210 (miR-210) expression in several cell types, including endothelial cells (ECs). In ECs, miR-210 represses EphrinA3 (EFNA3), inducing proangiogenic responses. This study provides new mechanistic evidences for a role of miR-210 in PACs. PACs were obtained from either adult peripheral blood or cord blood. miR-210 expression was modulated with either an inhibitory complementary oligonucleotide (anti-miR-210) or a miRNA mimic (pre-miR-210). Scramble and absence of transfection served as controls. As expected, hypoxia increased miR-210 in PACs. In vivo, migration toward and adhesion to the ischemic endothelium facilitate the proangiogenic actions of transplanted PACs. In vitro, PAC migration toward SDF-1α/CXCL12 was impaired by anti-miR-210 and enhanced by pre-miR-210. Moreover, ...
CXCL10 (chemokine (C-X-C motif) ligand 10), Authors: Frank Antonicelli, Philippe Bernard. Published in: Atlas Genet Cytogenet Oncol Haematol.
CXCL16 is a member of the CXC chemokine family and signals through the CXCR6 receptor. CXCL16 may play a role in attracting lymphocyte subsets
Human C-X-C Motif Chemokine 9 / Monokine Induced by Gamma Interferon (CXCL9 / MIG) standard, for use in running standard curves in AlphaLISA no-wash detection assay
Recombinant Human IP-10/CXCL10 produced inE. coliis a single, non-glycosylated polypeptide chain containing 77 amino acids and having a molecular mass of 8.5 kDa.
Human IL-8/CXCL8 HEK293 Cells Overexpression Lysate 10098-HNCH1L is validated in western blot (WB) as positive control. Sino Biological offers bulk order for high quality cell lysates which are produced in house.
References for Abcams Recombinant human CXCL5 protein (ab50039). Please let us know if you have used this product in your publication
References for Abcams Recombinant Mouse CXCL5 protein (ab57029). Please let us know if you have used this product in your publication
Scottish Drugs Forum (SDF) is a company limited by guarantee, registration no. 106295 with charitable status and is also a registered Scottish charity, registered SC 008075. ...
Scottish Drugs Forum (SDF) is a company limited by guarantee, registration no. 106295 with charitable status and is also a registered Scottish charity, registered SC 008075. ...
CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with ... CXCL12 (over-)expressing cancers might not sense the CXCL12 gradient released from the metastasis target tissues since the ... However, in breast cancer where SDF1/CXCL12 is also expressed by the cancer cells themselves along with CXCR4, CXCL12 ... "Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in cancer ...
Production of CXCL12, a chemokine, is regulated by mir-126. POU3F1, a factor required for the activation of the transcription ... CXCL12 binds the receptor CXCR4 actively counteracting apoptosis and recruiting progenitor cells to the site of injury. mir-126 ... mir-126 is also released with in these bodies are upon absorption in a neighbouring cell induce the CXCL12 dependant vascular ... "Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection". Sci Signal. 2 (100): ra81. doi: ...
NOX-A12 targets CXCL12 (C-X-C Chemokine Ligand 12), a key chemokine protein. Favorable results were reported in October, 2018 ...
"Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer." Cancer research 62, no. 20 (2002 ...
Like other chemokines, CXCL12 is involved with cell migration that contributes to inflammation. In regards to the CNS, CXCL12 ... The stromal cell-derived factor 1 (SDF1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein that in ... The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening ... "Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)". "BioGPS - your Gene Portal System". ...
NOX-A12 acts as antagonist for CXCL12/SDF-1, a chemokine involved in tumor growth. While the high-selectivity and tight-binding ... February 2014). "The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility ... and C-X-C Chemokine Ligand 12 (CXCL2). An example of an RNA aptamer therapy includes Pegaptanib (aka Macugen ® ), the only FDA- ...
It is now classified as a chemokine receptor able to bind the chemokines CXCL12/SDF-1 and CXCL11. The protein is also a ... Atypical chemokine receptor 3 also known as C-X-C chemokine receptor type 7 (CXCR-7) and G-protein coupled receptor 159 (GPR159 ... "The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes". The Journal of Biological ... "The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer". The Journal of Biological Chemistry. 283 ( ...
2005). "Identification of genes differentially expressed in T cells following stimulation with the chemokines CXCL12 and CXCL10 ...
In a preclinical PDA mouse model, FAP+ CAFs produced the chemokine CXCL12, which is bound by PDA cancer cells. Because FAP+ ... For instance, inhibiting chemokine receptor type 2 (CCR2), colony-stimulating factor-1 receptor (CSF-1R) and granulocyte ... One such mechanism is the release of cell-type specific chemokines. Another is the TME's capacity to posttranslationally alter ... They can also exclude them via biosynthesis of CXCL12. Conditionally depleting these cells from the stroma of an ectopic, ...
Still, they can perform complex functions including chemokine-production (in CD1c+ myeloid DCs), cross-presentation (in CD141+ ... CXCL12". J. Exp. Med. 198 (5): 823-30. doi:10.1084/jem.20020437. PMC 2194187. PMID 12953097. Liu YJ (2005). "IPC: professional ... "The Inducible CXCR3 Ligands Control Plasmacytoid Dendritic Cell Responsiveness to the Constitutive Chemokine Stromal Cell- ...
L-RNA aptamers have been obtained for the chemokines CCL2 and CXCL12, the complement components C5a and ghrelin. They are ...
"The Rap GTPases regulate B cell migration toward the chemokine stromal cell-derived factor-1 (CXCL12): Potential role for Rap2 ...
In the invasive edge of pancreatic carcinoma, a subset of CD133+CXCR4+ (receptor for CXCL12 chemokine also known as a SDF1 ...
Involvement of chemokines, such as SDF1 (CXCL12), the fibroblast growth factor (FGF), and the transforming growth factor β (TGF ... such as CXCR4 and CXCR7 chemokine receptors, in the "leader" cells. The growth factors and chemokines produced by stromal cells ...
The specific chemokines involved with each of these two processes is known: CXCL12 is related to migration and differentiation ... Still much is to be researched in this field, as certain chemokines like CXCR2 plays a role in inflammation and repair but in ... It has also been shown that chemokines are involved in guiding immune cells to sites of axon lesions to facilitate inflammation ... So then, chemokines are directly involved with both migration and differentiation of OPCs. ...
CXCL8 and CXCL12 with roughly equal potency of 10μM, but not migration induced by other non-chemokine chemoattractants such as ... Ala4 in CCL2 is also present in CCL3 but the corresponding residue is Leu in CXCL8 and Ile in CXCL12. Inclusion of Leu at ... Peptide 3' is a 12-amino acid linear peptide corresponding to amino acids 51 to 62 of mature human chemokine CCL2. It is formed ... NR58-3.14.3 also inhibits the recruitment of leukocytes (macrophages, T cells, B cells) due to the chemokine CCL2 in rat skin. ...
Copper homeostasis protein cutC homolog CXCL12: chemokine (C-X-C motif) ligand 12, SDF-1, scyb12 DDX50: DExD-box helicase 50 ...
Lathia JD.Chemokine CXCL12 in neurodegenerative diseases: an SOS signal for stem cell-based repair.Trends Neurosci. 2012 Oct;35 ... The role of the chemokines in migration of stem cells was demonstrated in 1997 when it was discovered that bone marrow stem ... Aiuti, A.; Webb, I. J.; Bleul, C.; Springer, T.; Gutierrez-Ramos, J. C. (January 6, 1997). "The chemokine SDF-1 is a ... Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor ...
... intravascular accumulations of the malignant B-cells fail to express key CXC chemokine receptor proteins particularly CxcL12 ...
While the engraftment of HSCs at these sites are still being elucidated, the interaction between the chemokine CXCL12 expressed ... 2011). "Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the ... These cells secrete high levels of CXCL12 and closely associate with sympathetic nerves that influence cytokine-induced ... 1999). "Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4". Developmental Biology. 213 (2): 442- ...
... is induced in the context of microenvironmental interactions by CXCR4/SDF1 (CXCL12) chemokine signaling and the molecular ...
Chemokine (C-X-C motif) ligand 12 (CXCL12) signaling via its receptor C-X-C chemokine receptor type 4 (CXCR4) is also involved ... CXCL12, FGF2, and GDNF all communicate via a network to mediate SSC functions. Spermatogonial stem cells are the precursors to ... in regulation of SSC fate decisions.CXCL12 is found in Sertoli cells in the basement membrane of the seminiferous tubules in ...
... has been reported to reduce chronic lymphocytic leukemia cell chemotaxis towards the chemokines CXCL12 and CXCL13, ... and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia". Blood. 119 (11): 2590-2594. doi:10.1182/blood ...
TGFβ or stem cell factor and chemokines CCL25, CXCL12 or CCRL1 etc. Essential part of T cell development forms process called ... chemokine receptor which recognizes chemokines CCL19 and CCL21, that are largely produced by mTECs in the medulla, and ...
... -dependent chemotaxis has been reported in response to the chemokines CXCL12/SDF-1 in T lymphocytes, CXCL13/BLC in B ... 2007). "DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin ...
As well CXCL12 (SDF-1) constitutively produced in the bone marrow promotes proliferation of progenitor B cells in the bone ... C4-CC chemokines), but a small number of CC chemokines possess six cysteines (C6-CC chemokines). C6-CC chemokines include CCL1 ... The third group of chemokines is known as the C chemokines (or γ chemokines), and is unlike all other chemokines in that it has ... CCL1 for the ligand 1 of the CC-family of chemokines, and CCR1 for its respective receptor. The CC chemokine (or β-chemokine) ...
CXCR4 (also known as fusin) is the receptor for a chemokine known as CXCL12 (or SDF-1) and, as with CCR5, is utilized by HIV-1 ... CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine ... However, CXCR6 is more closely related in structure to CC chemokine receptors than to other CXC chemokine receptors. ACKR3 was ... "The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes". The Journal of Biological ...
chemokine receptor activity. • receptor activity. • protein binding. • C-C chemokine receptor activity. • C-C chemokine binding ... Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene.[5] CCR6 ... "Entrez Gene: CCR6 chemokine (C-C motif) receptor 6".. *^ Wang K, Zhang H, Kugathasan S, Annese V, Bradfield JP, Russell RK, ... "Chemokine Receptors: CCR6". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ...
Ways include chemokine CCL2 nitration, which traps T cells in the stroma. Tumor vasculature helps tumors preferentially recruit ... mediated T cell trapping and CXCL12-regulated T cell exclusion. The first FDA-approved therapeutic monoclonal antibody was a ...
This chemokine elicits its effects on its target cells by binding to the chemokine receptor chemokine receptor CCR7. It ... 2004). "CCL19 and CXCL12 trigger in vitro chemotaxis of human mantle cell lymphoma B cells". Clin. Cancer Res. 10 (3): 964-71. ... Chemokine (C-C motif) ligand 19 (CCL19) is a small cytokine belonging to the CC chemokine family that is also known as EBI1 ... 2000). "Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and ...
CXCL1 · CXCL2 · CXCL3 · CXCL4 · CXCL5 · CXCL6 · CXCL7 · CXCL8/IL8 · CXCL9 · CXCL10 · CXCL11 · CXCL12 · CXCL13 · CXCL14 · CXCL15 ... Chemokine. CCL. CCL1 · CCL2 · CCL3 · CCL4 · CCL5 · CCL6 · CCL7 · CCL8 · CCL9 · CCL11 · CCL12 · CCL13 · CCL14 · CCL15 · CCL16 · ...
positive regulation of chemokine (C-X-C motif) ligand 2 production. • positive regulation of JUN kinase activity. • positive ... positive regulation of chemokine production. • cellular extravasation. • negative regulation of lipid storage. • negative ... positive regulation of chemokine biosynthetic process. • epithelial cell proliferation involved in salivary gland morphogenesis ...
... s are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte.[1] They are protein mediators typically produced by T cells to direct the immune system response by signaling between its cells. Lymphokines have many roles, including the attraction of other immune cells, including macrophages and other lymphocytes, to an infected site and their subsequent activation to prepare them to mount an immune response. Circulating lymphocytes can detect a very small concentration of lymphokine and then move up the concentration gradient towards where the immune response is required. Lymphokines aid B cells to produce antibodies. Important lymphokines secreted by the T helper cell include:[2] ...
These include: CCL14, CCL19, CCL20, CCL21, CCL25, CCL27, CXCL12 and CXCL13. This classification is not strict; for example, ... C chemokinesEdit. The third group of chemokines is known as the C chemokines (or γ chemokines), and is unlike all other ... C4-CC chemokines), but a small number of CC chemokines possess six cysteines (C6-CC chemokines). C6-CC chemokines include CCL1 ... CC chemokinesEdit. The CC chemokine (or β-chemokine) proteins have two adjacent cysteines (amino acids), near their amino ...
C-X-C chemokine receptor activity. • interleukin-8 binding. • G-protein coupled receptor activity. • chemokine receptor ... This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 ... "Chemokine Receptors: CXCR1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical ... chemokine-mediated signaling pathway. • interleukin-8-mediated signaling pathway. • neutrophil degranulation. • chemotaxis. ...
Elevated serum levels of macrophage-derived chemokine and thymus and activation-regulated chemokine in autistic children, J ... CXCL12, CXCL16. ... focus on chemokines and their receptors. Lühikokkuvõte, Crit ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase-8 activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL also binds the receptors DcR1 and DcR2, which do not contain a cytoplasmic domain (DcR1) or contain a truncated death domain (DcR2). DcR1 functions as a TRAIL-neutralizing decoy-receptor. The cytoplasmic domain of DcR2 is functional and activates NFkappaB. In cells expressing DcR2, TRAIL binding therefore activates NFkappaB, leading to transcription of genes known to antagonize the death signaling pathway and/or to promote inflammation. Application of engineered ligands that have variable affinity for different death (DR4 and DR5) and decoy receptors (DCR1 and DCR2) may allow selective targeting of cancer cells by controlling activation of Type 1/Type 2 pathways of cell death and single cell fluctuations. Luminescent iridium complex-peptide ...
... (IL-24) is a protein that in humans is encoded by the IL24 gene. IL-24 is a cytokine belonging to the IL-10 family of cytokines that signals through two heterodimeric receptors: IL-20R1/IL-20R2 and IL-22R1/IL-20R2. This interleukin is also known as melanoma differentiation-associated 7 (mda-7) due to its discovery as a tumour suppressing protein. IL-24 appears to control in cell survival and proliferation by inducing rapid activation of particular transcription factors called STAT1 and STAT3. This cytokine is predominantly released by activated monocytes, macrophages and T helper 2 (Th2) cells[5] and acts on non-haematopoietic tissues such as skin, lung and reproductive tissues. IL-24 performs important roles in wound healing, arthritis, psoriasis and cancer.[6][7][8] Several studies have shown that cell death occurs in cancer cells/cell lines following exposure to IL-24.[9][10] The gene for IL-24 is located on chromosome 1 in humans.[11] ...
... as well as chemokine and cytokine production, and expression of adhesion molecules such as E-selectin, ICAM-1, and VCAM-1. This ...
Entrez Gene: CXCL12 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)".. ... Gene za CXCL12 je lociran na ljudskom hromozomu 10.[16][17] Kod ljudi i miševa CXCL12 i CXCR4 imaju visok identitet sekvence: ... 2007). „Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in ... The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes". J. Biol. Chem. 280 (42): ...
positive regulation of chemokine biosynthetic process. • regulation of insulin secretion. • extrinsic apoptotic signaling ... Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini Reviews in Medicinal Chemistry. 5 (12 ...
... is sometimes used interchangeably among scientists with the term cytokine.[3] Historically, cytokines were associated with hematopoietic (blood and lymph forming) cells and immune system cells (e.g., lymphocytes and tissue cells from spleen, thymus, and lymph nodes). For the circulatory system and bone marrow in which cells can occur in a liquid suspension and not bound up in solid tissue, it makes sense for them to communicate by soluble, circulating protein molecules. However, as different lines of research converged, it became clear that some of the same signaling proteins which the hematopoietic and immune systems use were also being used by all sorts of other cells and tissues, during development and in the mature organism. While growth factor implies a positive effect on cell division, cytokine is a neutral term with respect to whether a molecule affects proliferation. While some cytokines can be growth factors, such as G-CSF and GM-CSF, others have an inhibitory effect on ...
The protein encoded by this gene is a member of the interleukin 1 cytokine family. Protein structure modeling indicated that this cytokine may contain a 12-stranded beta-trefoil structure that is conserved between IL1A (IL-A alpha) and IL1B (IL-1 beta). This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding distinct isoforms have been reported.[8]. ...
chemokine activity. • cytokine activity. • heparin binding. • protein binding. • CXCR3 chemokine receptor binding. ... C-X-C motif chemokine 11 is a small cytokine belonging to the CXC chemokine family that is also called Interferon-inducible T- ... "Entrez Gene: CXCL11 chemokine (C-X-C motif) ligand 11".. *^ a b Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue ... This chemokine elicits its effects on its target cells by interacting with the cell surface chemokine receptor CXCR3, with a ...
Interferon alfa 2b is an antiviral or antineoplastic drug, that was originally discovered in the laboratory of Charles Weissmann at the University of Zurich. It was developed at Biogen, and ultimately marketed by Schering-Plough under the tradename Intron-A. It has been used for a wide range of indications, including viral infections and cancers. This drug is approved around the world for the treatment of chronic hepatitis C, chronic hepatitis B, hairy cell leukemia, Behçet's disease, chronic myelogenous leukemia, multiple myeloma, follicular lymphoma, carcinoid tumor, mastocytosis and malignant melanoma. ...
2007). "Clinical importance and therapeutic implications of the pivotal CXCL12-CXCR4 (chemokine ligand-receptor) interaction in ... Gene za CXCL12 je lociran na ljudskom hromozomu 10.[16][17] Kod ljudi i miševa CXCL12 i CXCR4 imaju visok identitet sekvence: ... "The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes". J. Biol. Chem. 280 (42): ... CXCL12.[10] Kod raka dojke, međutim, povećano CXCL12 izražavanje određuje umanjeni rizik od metastaze.[11][12] ...
4-1BB is a type 2 transmembrane glycoprotein receptor belonging to the TNF superfamily, expressed on activated T Lymphocytes.[1] 4-1BBL (4-1BB ligand) is found on APCs (antigen presenting cells) and binds to 4-1BB. ...
In Klein's first author paper in development in 2001, she reported that the chemokine CXC12 and its receptor CXCR4 are ... IL-1R1 signaling regulates CXCL12-mediated T cell localization and fate within the central nervous system during West Nile ... CXCL12 limits inflammation by localizing mononuclear infiltrates to the perivascular space during experimental autoimmune ... In 2002, Klein helped discover that deficiency in Chemokine Receptor 2 (CCR2) decreased monocyte recruitment to the CNS which ...
... is one of only a few diseases directly and primarily caused by an aberrant chemokine, making its molecular ... July 2008). "CXCR4 dimerization and beta-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM ... WHIM syndrome results from autosomal dominant mutations in the gene for the chemokine receptor, CXCR4, resulting in a carboxy- ... 2011). "AMD3100 is a potent antagonist at CXCR4(R334X), a hyperfunctional mutant chemokine receptor and cause of WHIM syndrome ...
... and other chemokines to stimulate angiogenesis and thus the growth of a tumour. CAFs produce a number of proteins that are ... fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 ...
was similar to AUC for CXCL12 (0.6354; ) and CEA (0.6973; ) and higher than that for SCC-Ag (0.5384; ) in the diagnosis of EC ... Table 3: Diagnostic criteria for chemokine CXCL12 and its receptor (CXCR4), classical tumor markers (CEA and SCC-Ag), and C- ... The C-X-C motif chemokine 12 (CXCL12), also known as stromal cell-derived factor 1 (SDF-1), interacts with its specific ... Some researchers suggested the role of chemokine CXCL12 and its receptor CXCR4 in the development of EC, but these studies were ...
Structural Basis of CXCR4 Sulfotyrosine Recognition by the Chemokine SDF-1/CXCL12 ... Structural Basis of CXCR4 Sulfotyrosine Recognition by the Chemokine SDF-1/CXCL12 ... Structural Basis of CXCR4 Sulfotyrosine Recognition by the Chemokine SDF-1/CXCL12 ... Structural Basis of CXCR4 Sulfotyrosine Recognition by the Chemokine SDF-1/CXCL12 ...
... chemokine activity, chemokine receptor binding, CXCR chemokine receptor binding, adult locomotory behavior ... tr,Q80YV8,Q80YV8_RAT C-X-C motif chemokine ligand 12 OS=Rattus norvegicus GN=Cxcl12 PE=1 SV=1 ... IPR001811. Chemokine_IL8-like_dom. IPR033899. CXC_Chemokine_domain. IPR036048. Interleukin_8-like_sf. ... IPR001811. Chemokine_IL8-like_dom. IPR033899. CXC_Chemokine_domain. IPR036048. Interleukin_8-like_sf. ...
... chemokine (C-X-C motif) ligand 12), Authors: Giulia Gentile, Maria Guarnaccia, Sebastiano Cavallaro. Published in: Atlas Genet ... CXCL12--CHMP1A CXCL12--CSRP2BP CXCL12--CTTN CXCL12--CXCL12 CXCL12--GGPS1 CXCL12--HNMT CXCL12--NKAIN3 CXCL12--PALM CXCL12--PBX3 ... CXCL12--RPL35A CXCL12--RPS27A CXCL12--SRRM2 CXCL12--TUBGCP5 CXCR4--CXCL12 CXCR7--CXCL12 ECD--CXCL12 GRID1--CXCL12 HMGB1--CXCL12 ... CXCL12 Mutations. ICGC Data Portal. CXCL12 TCGA Data Portal. CXCL12 Broad Tumor Portal. CXCL12. OASIS Portal. CXCL12 [ Somatic ...
Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12).. Veldkamp CT1, ... Tyrosine sulfation of the chemokine receptor CXCR4 enhances its interaction with the chemokine SDF-1alpha. Given similar post- ... N-terminal domains from seven transmembrane chemokine receptors have been employed for structural studies of chemokine-receptor ... and that sulfotyrosine 21 binds a specific site on the chemokine that includes arginine 47. We conclude that the SDF-1alpha ...
Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression.  Ueda, Yoshihiro; Yang, Kaiyong; Foster, ...
Abstract 3275: Chemokine CXCL12 promotes vascular compensation in antiangiogenic resistance through CXCR7 in glioblastoma. ... Chemokine CXCL12 promotes vascular compensation in antiangiogenic resistance through CXCR7 in glioblastoma. [abstract]. In: ... Abstract 3275: Chemokine CXCL12 promotes vascular compensation in antiangiogenic resistance through CXCR7 in glioblastoma ... Abstract 3275: Chemokine CXCL12 promotes vascular compensation in antiangiogenic resistance through CXCR7 in glioblastoma ...
A CXCL12 gene variant CXCL12-A (CXCL12-G801A, a single nucleotide polymorphism in the 3 untranslated region) is associated with ... The chemokine CXCL12, also known as stromal cell-derived factor-1 (SDF-1), is a small protein that regulates leukocyte ... Polymorphism and circulating levels of the chemokine CXCL12 in colorectal cancer patients. Dimberg, Jan University College of ... Based on the suggested role of CXCL12 in the pathogenesis of cancer we examined the association of the gene variant CXCL12-A ...
... Christopher T. Veldkamp,1 Christoph Seibert, ... Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12) J Mol Biol. 2006; ... For example, the CXC chemokine stromal cell derived factor-1 (SDF-1, also known as CXCL12) and its receptor CXCR4 are essential ... 3B) unambiguously defined the location of two p38 molecules on the chemokine. Each p38 peptide bound the chemokine in the same ...
Among other chemokines, CXCL12 has recently attracted much attention in the brain as it has been shown that it can be produced ... Among other chemokines, CXCL12 has recently attracted much attention in the brain as it has been shown that it can be produced ... This chemokine system has been shown to play important roles in brain plasticity processes occurring during development but ... This chemokine system has been shown to play important roles in brain plasticity processes occurring during development but ...
When centrally administered, CXCL12 was found to have similar effects to a HFD. Injection of CXCL12 into the third cerebral ... we examined in rats whether HFD intake affects a specific chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, in the ... we examined in rats whether HFD intake affects a specific chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, in the ... These results, showing CXCL12 in the hypothalamus to be stimulated by a HFD and to mimic the effects of the HFD where its ...
The chemokine receptor CXCR7 interacts with the chemokines CXCL11 and CXCL12. During development, this ligand receptor system ( ... Developmental expression patterns of chemokines CXCL11, CXCL12 and their receptor CXCR7 in testes of common marmoset and human. ... CXCL12 mRNA was detectable in all developmental stages in marmosets. The CXCL12 protein was exclusively localized to Sertoli ... This pattern of CXCL12/CXCR7 indicates their involvement in regulatory processes that possibly orchestrate the interaction ...
... tyrosine sulfation may be of universal importance in chemokine signaling. N-terminal domains … ... Tyrosine sulfation of the chemokine receptor CXCR4 enhances its interaction with the chemokine SDF-1alpha. Given similar post- ... Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12) J Mol Biol. 2006 ... Tyrosine sulfation of the chemokine receptor CXCR4 enhances its interaction with the chemokine SDF-1alpha. Given similar post- ...
The Chemokine CXCL12 Cleaved Form SDF-1(5-67) is Involved in the Trabecular Cell Apoptosis via CXCR3 ... The Chemokine CXCL12 Cleaved Form SDF-1(5-67) is Involved in the Trabecular Cell Apoptosis via CXCR3 ... The Chemokine CXCL12 Cleaved Form SDF-1(5-67) is Involved in the Trabecular Cell Apoptosis via CXCR3. Invest. Ophthalmol. Vis. ... CXCL12 and SDF-1(5-67) effects on the TC viability were studied by microplate cytofluorometry and FCM in a TC model of induced ...
SDF-1/CXCL12) directs leukocyte migration, stem cell homing, and cancer metastasis through activation of CXCR4, which is also a ... nanomolar concentrations but binding partners promote self-association at higher concentrations to form a typical CXC chemokine ... Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12.. *Christopher T. Veldkamp, Christoph Seibert ... The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) directs leukocyte migration, stem cell homing, and cancer metastasis ...
CXCL12, Pre-B cell growth-stimulating factor, PBSF, hIRH, chemokine (C-X-C motif) ligand 12, validated in (PBV10266r-10), ... SDF-1beta (CXCL12), murine recombinant protein. SDF-1, CXCL12, Pre-B cell growth-stimulating factor, PBSF, hIRH, chemokine (C-X ... SDF-1, CXCL12, Pre-B cell growth-stimulating factor, PBSF, hIRH, chemokine (C-X-C motif) ligand 12, SDF1, SDF1B, TPAR1, SCYB12 ... Stromal cell-derived factor-1 β is a stromal derived CXC chemokine. It signals through CXCR4 receptor. Recombinant murine SDF-1 ...
Synthetic heparan sulfate dodecasaccharides reveal single sulfation site interconverts CXCL8 and CXCL12 chemokine biology. ... Carbohydrate Sequence, Cell Migration Assays, Leukocyte, Chemokine CXCL12, Heparitin Sulfate, Human Umbilical Vein Endothelial ... glucosamine dramatically interconverts regulation of in vitro and in vivo biology mediated by the two important chemokines, ...
C-X-C motif chemokine 12 (CXCL12), which is known to guide axons outside the neural tube and interneurons in the cortex, is ... Using mouse genetics, we dissected the influence of IPC-derived CXCL12 on TCAs and interneurons by showing that Cxcl12 ablation ... We propose that CXCL12 signals from IPCs link cortical neurogenesis to the progression of TCAs and interneurons spatially and ... We demonstrate that intermediate progenitors release the chemotactic cytokine CXCL12 to promote intracortical interneuron ...
N2 - The CXCL12 gamma chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein ... AB - The CXCL12 gamma chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein ... The CXCL12 gamma chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein binds ... abstract = "The CXCL12 gamma chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This ...
Through the establishment of joint collaborations with reputable manufacturers of top-quality life-science research products such as PeproTech Inc., BioGems has positioned itself to become a highly competitive source for a wide-range of recombinant protein and flow-cytometry reagents
... in the CXCL12 sequence strongly reduced the CXCR4 binding potency of this chemokine. In addition, CXCL12-1Cit showed ... Chemotactic activity of CXCL12 isoforms. CXCL12 (▪), CXCL12-1Cit (♦), CXCL12-3Cit (▴), and CXCL12-5Cit (○) were tested for ... CXCR4-dependent calcium signaling of citrullinated CXCL12. CXCL12 (▪), CXCL12-1Cit (♦), CXCL12-3Cit (▴), and CXCL12-5Cit (○) ... Three CXCL12 isoforms were synthesized for biologic characterization: CXCL12-1Cit, CXCL12-3Cit, and CXCL12-5Cit, in which Arg8 ...
Using this platform, we quantified the bone marrow (BM) distribution of individual CXCL12 chemokine proteins, both before and ... We found ubiquitous CXCL12 distributions with local enrichments but no long-range gradients, in contrast to current assumptions ... A 3D Tissue-wide Digital Imaging Pipeline for Quantitation of Secreted Molecules Shows Absence of CXCL12 Gradients in Bone ... G-CSF; HSPC; PLA; SDF1; bone marrow; chemokine; fluorescence microscopy; gradient; mobilization; secreted protein ...
... chemokine gene encodes the only natural ligand for CXCR4, the coreceptor for the pathogenic X4 HIV-1 strains. A single- ... The chemokine stromal-derived factor-1 (SDF-1, gene symbol CXCL12) and its receptor CXCR4 play critical roles in developmental ... Table 3 Survival analyses of progression to AIDS end points for CXCL12 SNPs and haplotypes using Cox proportional hazards ... The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 1996; 382: ...
... cxcl12) single-domain Antibody scFv Fragment is available from creative biolabs. ... chemokine (ccl2, ccl3, ccl5, cxcl11, cxcl12) single-domain; ccl2; ccl3; ccl5; cxcl11; cxcl12; chemokine (C-C motif) ligand 2; ... Chemokine (ccl2, Ccl3, Ccl5, Cxcl11, Cxcl12) Single-domain. *Recombinant Anti-chemokine (ccl2, ccl3, ccl5, cxcl11, cxcl12) ... cxcl12) single-domain Antibody Fab Fragment ( MOB-198-F(E) ) Recombinant Human Anti-chemokine (ccl2, ccl3, ccl5, cxcl11, cxcl12 ...
Within atherosclerotic plaques, CXCL12 can be detected in SMCs and ECs, and plasma levels of CXCL12 are decreased in patients ... The Chemokine CXCL10 and the T Cell Connection. CXCL10 or IP-10 (IFN-γ-induced protein of 10 kDa) is a T cell chemokine and ... Differential Chemokine Receptor Usage by Distinct Monocyte Subsets. *The Transmembrane Chemokine CX3CL1 and its Receptor CX3CR1 ... Differential Chemokine Receptor Usage by Distinct Monocyte Subsets. *The Transmembrane Chemokine CX3CL1 and its Receptor CX3CR1 ...
This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants. ... Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing ... This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential ... while the combination of chemokine plus IL-2/GM-CSF boosted the response even further [52]. As CXCL12 is implicated in tumor ...
The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival ... The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival Molyneaux, K. A., Zinszner, H ... 2003). The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development, 130(18), ...
The role of the chemokine CXCL12 in trabecular meshwork cell homeostasis. The chemokine CXCL12, also known as SDF-1, is ... In the eye, CXCL12 and its cognate receptor CXCR4 are expressed in various cells; however, little is known about CXCL12 in the ... Further, CXCL12 is proteolytically cleaved at both ends forming truncated derivatives with altered bioactivity. CXCL12 plays a ... We study the role of CXCL12 in TM cell biology, and its function in mesenchymal stem cell engraftment for therapeutic TM ...
Chemokine CXCL12. *Chemokines, CXC. *Chemokines, CXC: metabolism. *HIV Envelope Protein gp120. *HIV Envelope Protein gp120: ...
Chemokine CXCL12 / administration & dosage* * Chemokine CXCL12 / adverse effects * Chemokine CXCL12 / genetics * Chronic ...
  • Chemokines are a family of soluble chemotactic cytokines that bind to their cognate G-protein coupled receptors. (hindawi.com)
  • The CXCL12 protein functions as a ligand for two seven-transmembrane receptors (7-TMRs). (atlasgeneticsoncology.org)
  • Given similar post-translational modification of other receptors, including CCR5, CX3CR1 and CCR2b, tyrosine sulfation may be of universal importance in chemokine signaling. (nih.gov)
  • N-terminal domains from seven transmembrane chemokine receptors have been employed for structural studies of chemokine-receptor interactions, but never in the context of proper post-translational modifications known to affect function. (nih.gov)
  • To validate the role of two CXCL12 receptors we used sunitinib (VEGFR inhibitor), AMD3100 (CXCR4 inhibitor), CCX662 (CXCR7 inhibitor) alone or in combination. (aacrjournals.org)
  • We propose that CXCL12 receptors, CXCR4 and CXCR7, have unique roles in response to loss of VEGF signaling and subsequent hypoxia. (aacrjournals.org)
  • Chemokines direct homeostatic and proinflammatory immune responses by activating specific guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) to induce cell migration along a gradient of increasing concentration of chemokine. (pubmedcentralcanada.ca)
  • Peptides derived from the N-terminal domains of chemokine receptors bind specifically to their respective chemokine ligands ( 10 , 11 ). (pubmedcentralcanada.ca)
  • Other chemokine receptors, including CCR5, CCR2B and CX 3 CR1, are similarly modified at one or more tyrosine residues ( 15 - 18 ). (pubmedcentralcanada.ca)
  • Conversely, cytokines/chemokines and their receptors that were first described in the immune system have been recently found in the brain, in glial cells, and neurons themselves. (frontiersin.org)
  • To understand the involvement of chemokines in the effects of a HFD, we examined in rats whether HFD intake affects a specific chemokine, CXCL12, and its receptors, CXCR4 and CXCR7, in the hypothalamus together with the neuropeptides and whether CXCL12 itself acts similarly to a HFD in stimulating the neuropeptides and altering ingestion and locomotor behavior. (frontiersin.org)
  • Compared to low-fat chow, a HFD for 5 days significantly increased the expression of CXCL12 and its receptors, in both the paraventricular nucleus (PVN) where the neuropeptides enkephalin (ENK) and galanin were also stimulated and the perifornical lateral hypothalamus (PFLH) where orexin (OX) and melanin-concentrating hormone (MCH) were increased. (frontiersin.org)
  • In contrast, the HFD had no impact on expression of CXCL12 or its receptors in the arcuate nucleus (ARC) where the carbohydrate-related peptide, neuropeptide Y (NPY), was suppressed. (frontiersin.org)
  • Injection of CXCL12 into the third cerebral ventricle immediately anterior to the hypothalamus significantly stimulated the ingestion of a HFD, reduced novelty-induced locomotor activity, and increased expression of ENK in the PVN where the CXCR4 receptors were dense. (frontiersin.org)
  • These results, showing CXCL12 in the hypothalamus to be stimulated by a HFD and to mimic the effects of the HFD where its receptors are located, suggest that this chemokine system may have a role in mediating both the neuronal and behavioral effects induced by a fat-rich diet. (frontiersin.org)
  • Non-peptide specific antagonists of chemokine receptors CXCR3 and CXCR4 were tested in order to determine the receptor involved. (arvojournals.org)
  • In vitro the expression of the chemokine and of both receptors was differently enhanced by TNF-a and TGF-b2. (arvojournals.org)
  • We demonstrate that CXCL12 and its truncated form SDF-1(5-67) regulate the TC survival through two different chemokine receptors. (arvojournals.org)
  • In this update, we will highlight these recent developments, in particular the identification of components regulating the transcriptional machinery of the proatherogenic chemokine CCL5, distinct roles of its receptors CCR1 and CCR5 in plaque formation and immunobalance, and differential site- and stage-specific effects of T cell-activating chemokines and their receptors, eg, CXCL10 and CXCR3. (ahajournals.org)
  • The contribution of the transmembrane chemokines CX 3 CL1 and CXCL16 with their respective receptors CX 3 CR1 and CXCR6 in the recruitment of T cell and monocyte subsets and shear-mediated plaque modulation will be discussed. (ahajournals.org)
  • 1,2 By signaling through G protein-coupled chemokine receptors, chemokines govern a variety of cell responses including cell activation and transmigration in leukocytes, as well as in nonhematopoietic cells. (ahajournals.org)
  • The role of the CC chemokine ligand-5 (CCL5/RANTES) and its receptors CCR1 and CCR5 in atherosclerosis have been addressed in a number of studies. (ahajournals.org)
  • To date, there are more than 50 chemokines and 18 chemokine receptors identified [ 6 ]. (mdpi.com)
  • Most chemokines bind to more than one receptor, while most receptors also display overlapping ligand specificity [ 5 ]. (mdpi.com)
  • Molecular genetic epidemiological studies have identified polymorphisms in more than 20 human genes, including several chemokines and their receptors, that are associated with HIV-1 infection and/or AIDS disease pathogenesis. (nature.com)
  • An emerging number of non-chemokine mediators are found to bind to classical chemokine receptors and to elicit critical biological responses. (jpt.com)
  • Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that exhibits chemokine-like activities through non-cognate interactions with the chemokine receptors CXCR2 and CXCR4, in addition to activating the type II receptor CD74. (jpt.com)
  • CXCL12 and its receptors, CXCR4 and CXCR7, have been implicated in migration, proliferation and survival of gonocytes and their precursors and progeny, primordial germ cells and spermatogonial stem cells respectively. (edu.au)
  • All of these proteins exert their biological effects by interacting with G protein -linked transmembrane receptors called chemokine receptors , that are selectively found on the surfaces of their target cells. (wikipedia.org)
  • Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) prime endothelial cells to respond to "hematopoietic" chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. (ox.ac.uk)
  • We found that 4T1 breast cancer cells expressed high levels of CXCR7, but not of CXCR4, both of which are CXCL12 receptors. (nature.com)
  • More interestingly, breast cancer cells with high expression of CXCR4 and CXCR7, the chemokine receptors for CXCL12, are apt to migrate to the distant sites where CXCL12 is highly expressed. (nature.com)
  • It has been found that chemokines and their receptors serve a pivotal role in HCC progression. (spandidos-publications.com)
  • Thus, chemokines and their receptors directly or indirectly shape the tumor cell microenvironment, and regulate the biological behavior of the tumor. (spandidos-publications.com)
  • Exosomes containing chemokines or expressing receptors for chemokines may improve chemotaxis to HCC and may thus be exploited for targeted drug delivery. (spandidos-publications.com)
  • Chemokines bind to a variety of different receptors, which belong to the G-protein-binding receptor family, and there are ~23 types of chemokine receptors that have been discovered ( 10 ). (spandidos-publications.com)
  • Chemokines and their receptors were initially thought to allow for an interaction between immune cells and the inflammatory sites ( 11 ). (spandidos-publications.com)
  • After binding to the receptors, chemokines primarily serve a role in migration of leukocytes, such as monocytes, eosinophils and dendritic cells (DCs) ( 11 ). (spandidos-publications.com)
  • CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. (wikipedia.org)
  • Until recently, SDF-1 and CXCR4 were believed to be a relatively monogamous ligand-receptor pair (other chemokines are promiscuous, tending to use several different chemokine receptors). (wikipedia.org)
  • Chemokine receptors can be subdivided into specific families based on their specificity for C, CC, CXC, or CX3C chemokine ligands. (biomedcentral.com)
  • Our results reveal a specialized role for CXCR7 in endothelial biology and valve development and highlight the distinct developmental role of evolutionary conserved chemokine receptors such as CXCR7 and CXCR4. (pnas.org)
  • Chemokines are chemoattractant cytokines that bind to G protein-coupled seven-transmembrane receptors (GPCRs). (pnas.org)
  • Chemokines receptors are seven transmembrane spanning G protein-coupled receptors that allow cells to migrate towards increasing chemokine gradients. (biolegend.com)
  • Specific chemokine receptors are often required to gain entry (or exit) from certain organs and tissues like the thymus and bone marrow. (biolegend.com)
  • Chemokine signals are transduced by G-protein coupled receptors, which dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. (wikipathways.org)
  • The effect of combined polymorphisms in chemokines and chemokine receptors on the clinical course of HIV-1 infection in a Brazilian population. (curehunter.com)
  • 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. (curehunter.com)
  • Chemokines and their receptors were discovered about twenty years ago as mediators of leukocyte traffic. (biologists.org)
  • Whereas the primary role of chemokines is in the immune system, the homeostatic chemokine SDF-1/CXCL12 and its receptors CXCR4 and CXCR7 have been found to play crucial roles in a wide range of developmental processes. (biologists.org)
  • In this review, we discuss several examples of the roles that SDF-1/CXCL12 and its receptors play in early development. (biologists.org)
  • As we review here, these characteristics have enabled studies of the function of CXCL12 proteins (as a result of gene duplication, zebrafish possess two CXCL12-encoding genes, cxcl12a and cxcl12b ) and their receptors (CXCR4a, CXCR4b and CXCR7b in zebrafish) in controlling the migration of cells during gastrulation, primordial germ cell (PGC) migration, and the migration of cell clusters during the development of the zebrafish lateral line organ. (biologists.org)
  • Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation, and development. (sciencemag.org)
  • Chemokine receptors are G protein-coupled receptors (GPCRs) that, together with their small protein ligands, regulate the migration of many different cell types, most notably leukocytes ( 1 - 3 ). (sciencemag.org)
  • CXCR4, one of 19 known human chemokine receptors, is activated exclusively by the chemokine CXCL12 (also known as stromal cell-derived factor-1, SDF-1) and couples primarily through G i proteins. (sciencemag.org)
  • By revealing the link of certain chemokine receptors to neuronal survival and function, these discoveries have been instrumental in predicting potential consequence of chemokine alteration or manipulation under normal and pathological conditions, and in the exploration of new therapeutic approaches to reduce neuroinflammation and neuronal damage in the adult brain. (drexel.edu)
  • Discoveries concerning the regulation of the CXCR4 chemokine receptors by opiates, including morphine, have revealed unexpected factors responsible for HIV neuropathology that may be particularly relevant to the HIV+ population of drug users. (drexel.edu)
  • The homeostatic microenvironment chemokine CXCL12 binds the CXCR4 and CXCR7 receptors, activating divergent signals on multiple pathways, such as ERK1/2, p38, SAPK/JNK, AKT, mTOR, and the Bruton tyrosine kinase (BTK). (aacrjournals.org)
  • Chemokines act on chemokine receptors (CKR), members of the seven-transmembrane domain G-protein-coupled receptor (GPCR) superfamily. (aacrjournals.org)
  • We defined expression profiles of AAMφ-associated cytokines, chemokines, and their receptors, providing evidence that AAMφ contribute toward recruitment and maintenance of eosinophilia. (bloodjournal.org)
  • Chemokines bind to specific G-protein-coupled seven-span transmembrane receptors. (dovepress.com)
  • 2 , 3 Chemokine receptors are a family of G protein-coupled cell surface receptors (GPCRs) with seven transmembrane-spanning domains. (dovepress.com)
  • This double-feedback cross-talk underlies the polarised expression of chemokine receptors that is required for collective migration of the primordium ( Aman and Piotrowski, 2008 ). (biologists.org)
  • Chemokine receptors have been implicated in pancreatic cancer metastasis ( 3 ). (spandidos-publications.com)
  • BL-8040 selectively inhibits CXCR4 chemokine receptors. (genomeweb.com)
  • These receptors and its activating ligand CXCL12 spur the growth of AML cells in bone marrow. (genomeweb.com)
  • NOX-A12 is the only anti-cancer agent in active clinical development that neutralizes the CXCL12 ligand, thereby resulting in a complete block of CXCL12 signaling through its two receptors, CXCR4 and CXCR7. (pressebox.de)
  • Competing agents act at the receptor level and only inhibit one of the two CXCL12 receptors. (pressebox.de)
  • CXCL12 binds with high affinity to two chemokine receptors, CXCR4 and CXCR7. (pressebox.de)
  • Inhibition of the CXCL12 binding to its receptors sensitizes tumor cells to chemotherapy and in some solid tumors, prevents invasion and metastasis, suggesting that NOX-A12 in combination with chemotherapy could be beneficial in the treatment of various cancers. (pressebox.de)
  • Based on our knowledge, this study is the first to assess the serum concentration of chemokine CXCL12 and its specific receptor CXCR4 in the diagnosis of EC patients. (hindawi.com)
  • The serum concentrations of CXCL12 were significantly higher, while those of its receptor CXCR4 were significantly lower in EC patients compared to healthy controls. (hindawi.com)
  • Stem cell homing and breast cancer metastasis are orchestrated by the chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4. (sciencemag.org)
  • Our work elucidates the structural basis for sulfotyrosine recognition in the chemokine-receptor interaction and suggests a strategy for CXCR4-targeted drug development. (sciencemag.org)
  • Tyrosine sulfation of the chemokine receptor CXCR4 enhances its interaction with the chemokine SDF-1alpha. (nih.gov)
  • We conclude that the SDF-1alpha dimer preferentially interacts with receptor peptide, and residues beyond the extreme N-terminal region of CXCR4, including sulfotyrosine 21, make specific contacts with the chemokine ligand. (nih.gov)
  • CXCL12 as ligand and its receptor CXCR4 have been implicated in colorectal cancer (CRC) progression including angiogenesis and metastasis. (diva-portal.org)
  • For example, the CXC chemokine stromal cell derived factor-1 (SDF-1, also known as CXCL12) and its receptor CXCR4 are essential for proper fetal development. (pubmedcentralcanada.ca)
  • To define the basis for sulfotyrosine recognition in a chemokine-receptor signaling complex, we solved the structures of the extracellular N-terminal domain of CXCR4 in its unmodified, singly sulfated and fully sulfated forms when bound to its ligand SDF-1. (pubmedcentralcanada.ca)
  • Our nuclear magnetic resonance (NMR) studies revealed a symmetric 2:2 complex in which the binding of CXCR4 stabilized dimeric SDF-1 and each receptor sulfotyrosine occupied a unique site on the chemokine. (pubmedcentralcanada.ca)
  • These results provide the first view of sulfotyrosine recognition in a chemokine-receptor complex at atomic resolution and suggest a novel strategy for inhibition of CXCR4 signaling with oligomeric ligands. (pubmedcentralcanada.ca)
  • Developmental expression patterns of chemokines CXCL11, CXCL12 and their receptor CXCR7 in testes of common marmoset and human. (sigmaaldrich.com)
  • The chemokine receptor CXCR7 interacts with the chemokines CXCL11 and CXCL12. (sigmaaldrich.com)
  • Structure-Based Identification of Novel Ligands Targeting Multiple Sites within a Chemokine-G-Protein-Coupled-Receptor Interface. (semanticscholar.org)
  • Chemokine: receptor structure, interactions, and antagonism. (semanticscholar.org)
  • We demonstrate that intermediate progenitors release the chemotactic cytokine CXCL12 to promote intracortical interneuron migration and growth of thalamic axons via the cognate receptor CXCR4. (ox.ac.uk)
  • Unlike most chemokines whose function and expression are specific and centered around their role in leukocyte trafficking, both stromal cell-derived factor 1/CXCL12 and its first identified receptor CXCR4 were found to be expressed in a wide variety of cell types and tissues ( 3 ). (jimmunol.org)
  • In the context of cancer, the chemokine-chemokine receptor system plays paradoxical roles. (mdpi.com)
  • The chemokine stromal-derived factor-1 ( SDF-1 , gene symbol CXCL12 ) and its receptor CXCR4 play critical roles in developmental processes of the nervous, cardiovascular, and hematopoietic systems. (nature.com)
  • The chemokine CXCL12 and its receptor CXCR4 are implicated in human seminoma metastasis. (edu.au)
  • Fingerprint Dive into the research topics of 'The chemokine CXCL12 and its receptor CXCR4 are implicated in human seminoma metastasis. (edu.au)
  • Solving the structure of the chemokine SDF-1 bound to an extracellular domain of its receptor CXCR4 has illustrated the basis of receptor sulfotyrosine recognition by chemokines and led to the discovery of an inhibitor of leukocyte chemotaxis. (sciencemag.org)
  • The fimbriae of the bacteria that cause gingivitis promote the interaction of Toll-like receptor 2 (TLR2) and chemokine receptor CXCR4 to inhibit innate immunity. (sciencemag.org)
  • COVER This week's issue features a Research Article that reports the nuclear magnetic resonance (NMR) structure of the chemokine SDF-1 bound to the extracellular domain of its receptor CXCR4, thus demonstrating the basis for the recognition of receptor sulfotyrosine residues by the chemokine. (sciencemag.org)
  • To analyze the differences in gene expression levels of chemokine CXCL-12 and its receptor CXCR4 in gastric cancer and the relationship between their correlations with the clinical prognosis of gastric cancer. (cdc.gov)
  • Coculture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the "hematopoietic" chemokine CXCL12 and its CXCR4 receptor by day 3 of coculture. (ox.ac.uk)
  • A broad distribution of CXCR4, the main receptor of CXCL12, on numerous kinds of tumors might take into account neoplastic development [23, 24, 25]. (uitest.info)
  • These cells also possessed an engraftment defect impeding reconstitution in irradiated recipient mice, which was reversible by pretransplant administration of antagonists of the CXCL12 receptor, CXCR4. (jci.org)
  • C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene. (wikipedia.org)
  • The protein is a CXC chemokine receptor. (wikipedia.org)
  • CXCR-4 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. (wikipedia.org)
  • Expression of this receptor in cancer cells has been linked to metastasis to tissues containing a high concentration of CXCL12, such as lungs, liver and bone marrow. (wikipedia.org)
  • CXCL12 (over-)expressing cancers might not sense the CXCL12 gradient released from the metastasis target tissues since the receptor, CXCR4, is saturated with the ligand produced in an autocrine manner. (wikipedia.org)
  • CXCL12-induced chemotaxis is inhibited by pertussis toxin, enhanced in vitro by IL-3, and selectively inhibited by soluble ephrin-B receptor. (biomedcentral.com)
  • We noted differential expression of the chemokine receptor CXCR7 (RDC-1) on marginal zone B cells, a cell type associated with autoimmune diseases. (pnas.org)
  • CXCL12 (SDF-1) and its receptor CXCR4 are essential for heart, CNS, and blood vessel development, as well as B cell lymphopoiesis ( 3 - 7 ). (pnas.org)
  • However, recent studies show that CXCL12 binds to an additional chemokine receptor, CXCR7 (RDC1/Cmkor1) ( 8 , 9 ). (pnas.org)
  • It was first identified as an orphan GPCR expressed in the human thyroid and related to the chemokine receptor CXCR2 ( 10 ). (pnas.org)
  • We have studied the functional properties of a human T cell subset marked by the expression of CXC chemokine receptor 5 (CXCR5). (rupress.org)
  • CC chemokine receptor 7 (CCR7), the selective receptor for SLC and ELC, is present on the bulk of resting T cells in peripheral blood and mature dendritic cells and mediates rapid adhesion to integrin ligands and chemotactic migration ( 1 )( 2 )( 3 )( 4 )( 6 )( 7 ). (rupress.org)
  • CXCL12 binds the receptor CXCR4 actively counteracting apoptosis and recruiting progenitor cells to the site of injury. (wikipedia.org)
  • Use this table to quickly identify the chemokines that bind to each receptor. (biolegend.com)
  • Nagasawa T. CXC chemokine ligand 12 (CXCL12) and its receptor CXCR4. (springer.com)
  • Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. (abcam.com)
  • Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. (abcam.com)
  • Naturally occurring modifications, such as N-terminal truncation, can affect the biological potency and the receptor specificity of chemokines. (rndsystems.com)
  • Here, we review the roles of the chemokine stromal cell-derived factor 1 (SDF-1/CXCL12) and its receptor CXCR4 during zebrafish and mouse embryonic development, and discuss their function in regulating the interactions of cells with their extracellular environment, in directing their migration, and in maintaining their location. (biologists.org)
  • The G protein-coupled chemokine receptor CXCR4 is specifically implicated in cancer metastasis and HIV-1 infection. (sciencemag.org)
  • These efforts have focused on the CXCL12/CXCR4 and the CX3CL1/CX3CR1 chemokine-receptor pairs, which are both constitutively expressed in the CNS and involved in essential neuronal and glia functions. (drexel.edu)
  • Long-term collaborative studies with Dr. Alessandro Fatatis (College of Medicine) have focused on the role of the chemokine receptor CX3CR1 in skeletal metastasis. (drexel.edu)
  • Evidence suggests that the CXC-chemokine receptor-4 pathway plays a role in cancer cell homing and metastasis, and thus represents a potential target for cancer therapy. (aacrjournals.org)
  • Human CXCR4 was originally identified as a receptor for CXCL12 by screening CKR orphan genes for their ability to induce intracellular Ca +2 in response to human CXCL12. (aacrjournals.org)
  • The CXC chemokine receptor-4 (CXCR4) plays a critical role in cancer by positively regulating cancer cell metastasis and survival. (aacrjournals.org)
  • We have focused on CXC chemokine receptor-4 (CXCR4), which is upregulated in at least 23 different cancers ( 3 ). (aacrjournals.org)
  • [9] CXCL12 takođe ima ulogu u metastazi tumora gde su ćelije raka koje izražavaju CXCR4 receptor privučene ka metastaznim ciljnim tkivima koja oslobađaju ligand, CXCL12. (wikipedia.org)
  • [13] CXCL12-CXCR4 interakcija je nekad bila smatrana eksluzivnom (za razliku od drugih hemokina i njihovih receptora), ali je nedavno bilo predloženo da se CXCL12 možda takođe vezuje za CXCR7 receptor. (wikipedia.org)
  • C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12). (dovepress.com)
  • 4 , 5 The chemokine receptor CXCR4 is a 352-amino acid rhodopsin-like GPCR that selectively binds to the CXC chemokine SDF-1 or CXCL12. (dovepress.com)
  • Stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) are important regulators of the development of the dentate gyrus (DG). (jneurosci.org)
  • also known as CXCL12) via its receptor CXC chemokine receptor 4 (CXCR4) has been shown to be of great importance in the development of many tissues including the nervous system ( Tran and Miller, 2003 ). (jneurosci.org)
  • The present study demonstrates that paired box transcription factor 6 (PAX6) and C‑X‑C chemokine receptor 4 (CXCR4) are frequently co‑expressed in primary pancreatic adenocarcinoma tumors and established cell lines. (spandidos-publications.com)
  • In particular, C-X-C chemokine receptor 4 (CXCR4), a chemokine G-protein-coupled receptor, is frequently expressed in pancreatic cancer and affects pancreatic tumor cell growth, adhesion, migration and invasion in cellulo and in clinical samples ( 4 - 8 ). (spandidos-publications.com)
  • Atypical Chemokine Receptor 3 CXC Chemokine Receptor Type 7 or Chemokine Orphan Receptor 1 or G Protein Coupled Receptor 159 or G Protein Coupled Receptor RDC1 Homolog or GPR159 or CXCR7 or ACKR3 pipeline Target constitutes close to 6 molecules. (bioportfolio.com)
  • Atypical Chemokine Receptor 3 CXC Chemokine Receptor Type 7 or Chemokine Orphan Receptor 1 or G Protein Coupled Receptor 159 or G Protein Coupled Receptor RDC1 Homolog or GPR159 or CXCR7 or ACKR3 Atypical chemokine receptor 3 is a protein encoded by the ACKR3 gene. (bioportfolio.com)
  • It acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. (bioportfolio.com)
  • It also reviews key players involved in Atypical Chemokine Receptor 3 CXC Chemokine Receptor Type 7 or Chemokine Orphan Receptor 1 or G Protein Coupled Receptor 159 or G Protein Coupled Receptor RDC1 Homolog or GPR159 or CXCR7 or ACKR3 targeted therapeutics development with respective active and dormant or discontinued projects. (bioportfolio.com)
  • Bias in chemokine receptor signalling. (semanticscholar.org)
  • Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T(GFP) cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T(GFP) cell behavior. (nih.gov)
  • The cycling postnatal HSCs expressed high levels of CXC chemokine ligand 12 (CXCL12, also known as stromal cell-derived factor 1 [SDF-1]), a chemokine previously implicated in stem cell trafficking to the marrow cavity and shown to be expressed by cells within the hematopoietic microenvironment. (jci.org)
  • The CXC chemokine ligand-12 (CXCL12) is a member of the CXC chemokine subfamily that is constitutively expressed in the bone marrow and other tissues including the brain endothelium and is responsible for regulating the trafficking and localization of bone marrow progenitor cells under steady state and stress conditions. (ahajournals.org)
  • NOX-A12 specifically antagonizes CXCL12/SDF-1 (CXC Chemokine Ligand 12 / Stromal Cell-Derived Factor-1), a chemokine which attracts and activates immune and non-immune cells including stem cells from the bone marrow. (pressebox.de)
  • CXCL12 gene encodes a stromal cell-derived alpha chemokine, also known as SDF1, a member of the intercrine family. (atlasgeneticsoncology.org)
  • Evaluation alongside dodecasaccharides lacking this single glucosamine O6-sulfation, or having per-O6-sulfation, shows that site-specific modification of the terminal glucosamine dramatically interconverts regulation of in vitro and in vivo biology mediated by the two important chemokines, CXCL12 (SDF1α) or CXCL8 (IL-8). (manchester.ac.uk)
  • However, in breast cancer where SDF1/CXCL12 is also expressed by the cancer cells themselves along with CXCR4, CXCL12 expression is positively correlated with disease free (metastasis free) survival. (wikipedia.org)
  • Prognostic significance of CXCL12, CXCR4, and CXCR7 in patients with breast cancer. (cdc.gov)
  • Conclusions: Our results suggests a compensatory response of vasculomegaly to trimming of small vessels by sunitinib may be mediated by CXCL12 in a CXCR7 dependent process. (aacrjournals.org)
  • Chemokine CXCL12 promotes vascular compensation in antiangiogenic resistance through CXCR7 in glioblastoma. (aacrjournals.org)
  • Real-time quantitative polymerase chain reaction was performed in monkeys to detect CXCL11, CXCL12 and CXCR7. (sigmaaldrich.com)
  • At the protein level, CXCL12 and CXCR7 were localized in the testes of the marmoset (Callitrix jacchus) whereas CXCR7 patterns were determined for various stages in human testes. (sigmaaldrich.com)
  • This pattern of CXCL12/CXCR7 indicates their involvement in regulatory processes that possibly orchestrate the interaction between undifferentiated germ cells and Sertoli cells. (sigmaaldrich.com)
  • However, the CXCR7-binding capacities of CXCL12-1Cit and CXCL12-3Cit were, respectively, intact and reduced, whereas CXCL12-5Cit failed to bind CXCR7. (jimmunol.org)
  • In presence of CXCL12, CXCR7 expression on tumour cells was decreased. (nature.com)
  • Therefore, our data demonstrated that sustained expression of CXCL12 by MSCs in the primary tumour site inhibits metastasis through reduction of CXCR7, while, in the presence of TGFβ, this CXCL12 effect of MSCs on tumour cells is relieved. (nature.com)
  • Importantly, elevated CXCR7 and depressed CXCL12 expression levels were prominent features of clinical breast cancer lesions and were related significantly with poor survival. (nature.com)
  • We confirmed that the principal chemokine ligand for CXCR7 was CXCL12/SDF-1, which also binds CXCR4. (pnas.org)
  • however, CXCR7 formed functional heterodimers with CXCR4 and enhanced CXCL12-induced signaling. (pnas.org)
  • In addition to CXCL12, CXCR7 binds to the chemokine CXCL11, although with a lower affinity ( 9 ). (pnas.org)
  • Cxcr7 gene conservation throughout evolution and the affinity of CXCR7 for CXCL12 suggest that Cxcr7 may also play a role in lymphopoiesis or embryogenesis. (pnas.org)
  • The CXCL12 / CXCR4 / CXCR7 axis has been shown to play a role in stem cell mobilization, vasculogenesis, tumor growth and metastasis. (pressebox.de)
  • Many chemokine signaling pathways are also vital for cell migration in normal development or in abnormal conditions such as tumor metastasis. (pubmedcentralcanada.ca)
  • The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) directs leukocyte migration, stem cell homing, and cancer metastasis through activation of CXCR4, which is also a coreceptor for T-tropic HIV-1. (semanticscholar.org)
  • CXC chemokine recepter-4 (CXCR4) and its ligand, stromal cell-derived factor-1alpha (SDF-1alpha) have been implicated in the organ-specific metastasis of several malignancies. (nih.gov)
  • These findings indicate that CXCL12 expression in the human testis may selectively influence seminoma migration and metastasis, correlating with its importance in gonocyte and spermatogonial stem cell biology. (edu.au)
  • The expression of CXCL12 and CXCR4 in gastric cancer and their correlation to lymph node metastasis. (cdc.gov)
  • Interestingly, we found that MSC-produced CXCL12, an important chemokine in tumour metastasis, was markedly inhibited by TGFβ. (nature.com)
  • Furthermore, silencing of CXCL12 in TGFβ-unresponsive MSCs restored their ability to promote tumour metastasis. (nature.com)
  • The contributions of MSCs to breast cancer metastasis are mostly mediated through their ability to produce a number of factors, such as CCL5, CXCL12, which in turn exert paracrine actions on breast cancer cells that resulted in their invasion and/or distant organ metastasis. (nature.com)
  • 17 Beside its role in supporting tumour growth and angiogenesis, CXCL12 was demonstrated to be important in helping select metastatic tumour cells for bone metastasis. (nature.com)
  • Chemokines are involved in the inflammatory response, tumor immune response, proliferation, invasion and metastasis via modulation of various signaling pathways. (spandidos-publications.com)
  • It has been found that chemokine networks may serve pivotal roles in inducing organ-specific metastasis ( 8 ). (spandidos-publications.com)
  • Due to their function of targeting cells to specific organs, homeostatic chemokines can also be involved in cancer and metastasis. (biolegend.com)
  • CXCL12-CXCR4 contributes to the implication of bone marrow in cancer metastasis. (springer.com)
  • We previously showed that high concentrations of the CXCR4 ligand, wild-type CXCL12 (wtCXCL12), could inhibit colorectal cancer metastasis in vivo , and we have hypothesized that wtCXCL12 dimerizes at high concentration to become a potent antagonist of CXCR4. (aacrjournals.org)
  • Chemokine signaling plays a crucial role in cancer metastasis, neoangiogenesis, and proliferation as well as infiltration of tumor-associated immune cells ( 1, 2 ). (aacrjournals.org)
  • Recently, we reported that exogenous administration of CXCL12, the ligand of CXCR4, inhibits colorectal cancer metastasis ( 6 ). (aacrjournals.org)
  • CXCL12 2 was a more potent inhibitor of colorectal metastasis than wtCXCL12. (aacrjournals.org)
  • Using this platform, we quantified the bone marrow (BM) distribution of individual CXCL12 chemokine proteins, both before and after their depletion by granulocyte-colony stimulating factor (G-CSF) treatment. (nih.gov)
  • Chemokines (Greek -kinos , movement) are a family of small cytokines , or signaling proteins secreted by cells . (wikipedia.org)
  • Cytokine proteins are classified as chemokines according to behavior and structural characteristics. (wikipedia.org)
  • Chemokines are a class of small molecular proteins with similar structures, functions and chemotactic properties, and their molecular weights are ~10 kDa, and chemokines represent the largest member of the cytokine family ( 9 ). (spandidos-publications.com)
  • Chemokines comprise a large family of structurally related chemoattractant proteins that regulate the composition of cellular infiltrates at sites of inflammation or, alternatively, the physiological leukocyte migration during hematopoiesis, antigen sampling in secondary lymphoid tissues, and immune surveillance ( 1 )( 2 )( 3 )( 4 )( 5 )( 6 ). (rupress.org)
  • Chemokines are a family of small cytokines , or proteins secreted by cells . (wikidoc.org)
  • Proteins are classified as chemokines according to shared structural characteristics such as small size (they are all approximately 8-10 kilodaltons in size), and the presence of four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. (wikidoc.org)
  • Proteins are classified into the chemokine family based on their structural characteristics, not just their ability to attract cells. (wikidoc.org)
  • Typical chemokine proteins are produced as pro-peptides , beginning with a signal peptide of approximately 20 amino acids that gets cleaved from the active (mature) portion of the molecule during the process of its secretion from the cell. (wikidoc.org)
  • Chemokines are small cytokines, or signaling proteins, secreted by cells. (wikipathways.org)
  • Chemokines are small secreted proteins that function in leukocyte trafficking, recruitment, and activation and have a role in many pathophysiological processes such as infectious and autoimmune diseases, inflammation, cancer, and vascular disease. (rndsystems.com)
  • Chemokines (chemotactic cytokines) are a group of vertebrate-specific small (8-14 kDa) proteins that, depending on the presence and the position of conserved cysteine residues, are categorized into four subgroups (C, CC, CXC and CX3C). (biologists.org)
  • Chemokines are small, structurally related proteins that play a significant role in leukocyte trafficking and are divided into four groups (CXC, CC, C, and CX3C) based on the position of the first two conserved cysteines. (dovepress.com)
  • The chemokines are a family of small proteins that have been widely studied because of their key role in orchestrating the migration of leukocytes during inflammatory responses. (jneurosci.org)
  • Chemokines are a family of small cytokines, or proteins secreted by cells, with a molecular mass between 8 and 10 kDa. (genscript.com)
  • GenScript offers a comprehensive catalog of chemokine proteins with excellent lot-to-lot consistency, superior activity and significantly low endotoxin levels. (genscript.com)
  • The chemokine CXCL12/stromal cell-derived factor 1 alpha has first been described in the immune system where it functions include chemotaxis for lymphocytes and macrophages, migration of hematopoietic cells from fetal liver to bone marrow and the formation of large blood vessels. (frontiersin.org)
  • In chemotaxis assays with lymphocytes and monocytes, CXCL12-3Cit and CXCL12-5Cit were completely devoid of activity, whereas CXCL12-1Cit, albeit at higher concentrations than CXCL12, induced migration. (jimmunol.org)
  • For example, in addition to chemotaxis, chemokines modulate lymphocyte development, priming and effector function [ 2 ] and play a critical role in immune surveillance. (mdpi.com)
  • In addition to being known for mediating chemotaxis, chemokines are all approximately 8-10 kilodaltons in mass and have four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. (wikipedia.org)
  • In addition, the potential application of chemokines in chemotaxis of exosomes as drug vehicles is discussed. (spandidos-publications.com)
  • Chemokines are a class of cytokines that induce chemotaxis (migration) of target cells. (biolegend.com)
  • While some chemotaxis is induced by inflammation or damaged cells, other chemokines function in homeostasis. (biolegend.com)
  • The best-characterized role of chemokines is in the control of cell trafficking and activation as part of the immune response ( Luster, 1998 ), where they direct the movement of responsive cells towards higher concentrations of their ligand in the environment (a process termed chemotaxis). (biologists.org)
  • CXCL12 binding to CXCR4 triggers multiple signal transduction pathways that are able to regulate intracellular calcium flux, chemotaxis, transcription, and cell survival ( 8 ). (aacrjournals.org)
  • Although both can include a number of organic and inorganic substances, the most commonly researched inducers of chemotaxis are chemokines, or cytokines secreted by cells for the purpose of driving cellular movement and activation. (peprotech.com)
  • Considering the significance of chemotaxis in cellular movement during a number of biological processes, including immune response and development, it is of no surprise that a relatively large amount of emphasis has been placed upon research concerning chemotaxis and, more specifically, the Chemokines functioning to direct cellular movement. (peprotech.com)
  • The serum concentrations of CXCL12 and CXCR4 and classical tumor markers such as carcinoembryonal antigen (CEA) and squamous cell cancer antigen (SCC-Ag) were measured using immunoenzyme assays, while C-reactive protein (CRP) levels were assessed by immunoturbidimetric method. (hindawi.com)
  • To assess the impact of CXCL12 signaling on the vasculature and its ability to recruit progenitor cells, we combined a fluorescent chimeric mouse model and in vivo imaging to capture the chronological interactions among tumor cells (RFP), circulating BMDCs (GFP) and the cerebral vessels (FITC dextran) during tumor growth. (aacrjournals.org)
  • Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs) and effector cells to appropriate anatomical sites. (mdpi.com)
  • The CXCL12/CXCR4 axis takes part in a series of physiological, biochemical, and pathological process, such as inflammation and leukocyte trafficking, cancer-induced bone pain, and postsurgical pain, and also is a key factor in the cross-talking between tumor cells and their microenvironment. (bvsalud.org)
  • In conclusion, the CXCL12/CXCR4 signaling is important for tumor development and targeting the pathway might represent an effective approach to developing novel therapy in cancer treatment. (bvsalud.org)
  • Another explanation of this observation is provided by a study that shows the ability of CXCL12 (and CCL2) producing tumors to entrain neutrophils that inhibit seeding of tumor cells in the lung. (wikipedia.org)
  • Tumor PD-L1 altered tumor chemokines (e.g. (aacrjournals.org)
  • Tumor PD-L1 alteration of immune infiltrates by altering chemokines is a novel mechanism for PD-L1 TIL control. (aacrjournals.org)
  • Finally, αPD-L1 directly altered tumor cell chemokine production in vitro, suggesting additional, novel αPD-L1 treatment mechanisms requiring more study. (aacrjournals.org)
  • Targeting the CXCR4-CXCL12 axis thus offers the possibility of affecting CXCR4-expressing primary tumor cells, modulating the immune response, or synergizing with other targeted anticancer therapies. (aacrjournals.org)
  • Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12). (nih.gov)
  • The chemokine CXCL12, also known as stromal cell-derived factor-1 (SDF-1), is a small protein that regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. (diva-portal.org)
  • In this study, we describe modification of the CXC chemokine stromal cell-derived factor 1α/CXCL12 by peptidylarginine deiminase (PAD) that converts arginine residues into citrulline (Cit), thereby reducing the number of positive charges. (jimmunol.org)
  • The stromal-derived factor-1 ( SDF-1 ) chemokine gene encodes the only natural ligand for CXCR4, the coreceptor for the pathogenic X4 HIV-1 strains. (nature.com)
  • Chemokine 12 (CXCL12), also known as stromal cell derived factor-1 (SDF-1) and a member of the CXC chemokine subfamily, is ubiquitously expressed in many tissues and cell types. (bvsalud.org)
  • Stromal cell produced element 1 (SDF 1), or CXCL12 can be an essential person in the chemokine family members, and a powerful chemoattractant for hematopoietic stem cells and several leukocytes. (uitest.info)
  • Tonsillar CXCR5 + T cells do not respond to other chemokines present in secondary lymphoid tissues, including secondary lymphoid tissue chemokine (SLC), EBV-induced molecule 1 ligand chemokine (ELC), and stromal cell-derived factor 1 (SDF-1). (rupress.org)
  • Here, we analyzed the functional role of a chemokine, namely, stromal cell-derived factor 1α (SDF-1α), in the navigation of the perforant fibers. (jneurosci.org)
  • 1 The CXC chemokine stromal-derived-factor-1 (SDF-1 or CXCL12) is expressed in a variety of cells, including stromal cells (fibroblasts and endothelial cells). (dovepress.com)
  • Syndecan-4 is a signaling molecule for stromal cell-derived factor-1 (SDF-1)/ CXCL12. (semanticscholar.org)
  • Stromal cell-derived factor-1 (SDF-1)/CXCL12, the ligand for CXCR4, induces signal transduction. (semanticscholar.org)
  • Indeed, CXCL12 has been discovered rather as a cytokine that promotes pre-B cell growth ( 9 ), before its chemotactic effect was elucidated ( 10 ). (jimmunol.org)
  • Interleukin (IL)-6, a multifunctional cytokine with regulatory functions in wound healing, and several chemokines have been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD). (arvojournals.org)
  • Magnetic bead-based assays for detecting 46 mouse cytokine, chemokine, and growth factor biomarkers. (bio-rad.com)
  • Interestingly, and despite reduced agonist potency on CXCR4, the sustained binding of CXCL12 gamma to HS enabled it to promote in vivo intraperitoneal leukocyte accumulation and angiogenesis in matrigel plugs with much higher efficiency than CXCL12a. (monash.edu)
  • Chemokines are small cytokines, structurally characterized by conserved cysteine residues and first described for their ability to control leukocyte migration under basal and inflammatory conditions ( 1 , 2 , 3 , 4 ). (jimmunol.org)
  • Chemokines are involved in many biological activities ranging from leukocyte differentiation to neuronal morphogenesis. (biomedcentral.com)
  • Leukocyte traffic through secondary lymphoid tissues is finely tuned by chemokines. (rupress.org)
  • and homeostatic chemokines, which are constitutively produced and control homeostatic leukocyte traffic, secondary lymphoid organ structure and processes not related to the immune system. (biologists.org)
  • In adult vertebrates, chemokines are essential for proper lymphoid organ architecture and for leukocyte trafficking ( 1 ). (aacrjournals.org)
  • This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs. (nih.gov)
  • C-X-C motif chemokine 12 (CXCL12), which is known to guide axons outside the neural tube and interneurons in the cortex, is expressed in the meninges and IPCs. (ox.ac.uk)
  • Here, we report the therapeutic effect of either bone marrow-derived cells (BMDCs) or the stem cell chemo-attractant C-X-C motif chemokine 12 (CXCL12) on endometrial receptivity in a murine ethanol induced thin endometrium model. (elsevier.com)
  • The unsurpassed capacity to bind to HS on the extracellular matrix would make CXCL12 gamma paradigm of haptotactic protein, which regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells. (monash.edu)
  • Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. (curehunter.com)
  • CXCL12 exists in a monomer-dimer equilibrium in which both states bind CXCR4 and stimulate a calcium response, but only the monomeric variant promotes cell migration ( 7, 8 ). (aacrjournals.org)
  • Some inflammatory chemokines have proven essential in memory T cell generation [ 3 ]. (mdpi.com)
  • Inflammatory chemokines function mainly as chemoattractants for leukocytes , recruiting monocytes , neutrophils and other effector cells from the blood to sites of infection or tissue damage. (wikipedia.org)
  • Certain inflammatory chemokines activate cells to initiate an immune response or promote wound healing . (wikipedia.org)
  • In addition, several typical inflammatory chemokines are upregulated in inflamed rather than resting LNs, which may reflect an enhanced T cell activation status. (rupress.org)
  • These chemokines also have a more diverse range of functions compared to inflammatory chemokines. (biolegend.com)
  • In the event of infection, injury, or tissue damage, inflammatory chemokines are often released to address the problem. (biolegend.com)
  • Many inflammatory chemokines attract a wide variety of cells in both the innate and adaptive arms of immunity. (biolegend.com)
  • Review on CXCL12, with data on DNA, on the protein encoded, and where the gene is implicated. (atlasgeneticsoncology.org)
  • The CXCL12 gene consists of 4 exons spanning 14.94 kb on the chromosome 10 at band q11.21 (reverse strand) (Figure 1). (atlasgeneticsoncology.org)
  • A CXCL12 gene variant CXCL12-A (CXCL12-G801A, a single nucleotide polymorphism in the 3 untranslated region) is associated with increased susceptibility to breast cancer. (diva-portal.org)
  • Based on the suggested role of CXCL12 in the pathogenesis of cancer we examined the association of the gene variant CXCL12-A with CRC. (diva-portal.org)
  • The CXCL12 gamma chemokine arises by alternative splicing from Cxcl12, an essential gene during development. (monash.edu)
  • Importantly, mutant mice with a targeted deletion of the CXCL12 gene die perinatally, because of marked defects in cardiac septal formation and vascularization of the gastrointestinal tract ( 11 ). (jimmunol.org)
  • This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. (mdpi.com)
  • Together, these results provide insight into chemokine-induced gene activation and identify potentially novel functions for known genes in chemokine biology. (biomedcentral.com)
  • Gene za CXCL12 je lociran na ljudskom hromozomu 10 . (wikipedia.org)
  • The CXCL12-CXCR4 axis is the focus of this Molecular Pathways review. (aacrjournals.org)
  • The amino-terminal domain of CXCL12 binds the second extracellular loop of CXCR4 and activates downstream signaling pathways. (aacrjournals.org)
  • Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression. (duke.edu)
  • Besides their effect on the immune system, cytokines can also act in the brain to modulate our behaviors, inducing, for example, anorexia upon inflammation when produced in large amount, but cytokines/chemokines could also play a key role in the brain even in non-pathological conditions. (frontiersin.org)
  • Posttranslational proteolytic processing of chemokines is a natural mechanism to regulate inflammation. (jimmunol.org)
  • Chemokines can be located in different vascular cell types, eg, endothelial cells (ECs) but also inflammatory cells and can be detected within atherosclerotic lesions, where they function as messengers to direct leukocytes to sites of inflammation but may also control homeostasis and other activities of emigrated cells. (ahajournals.org)
  • Within this area, specific interests include the role of cc chemokines in inflammation, their interaction with cell surface glycosaminoglycans and signal transduction mechanisms mediated by them. (ncl.ac.uk)
  • My work so far has helped in clearly defining the role of chemokines in inflammation with particular relevance to transplantation. (ncl.ac.uk)
  • In good agreement, mutant CXCL12 chemokines selectively devoid of HS-binding capacity failed to promote in vivo significant cell recruitment. (monash.edu)
  • Memory but not naive T cells from tonsils are CXCR5 + and migrate in response to the B cell-attracting chemokine 1 (BCA-1), which is selectively expressed by reticular cells and blood vessels within B cell follicles. (rupress.org)
  • Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T(GFP) cells). (nih.gov)
  • According to UCSC Genome Browser on Human Feb. 2009 assembly (GRCh37/hg19), genes flanking CXCL12 on 10q11.21, in centromere to telomere direction, are ZNF32 (zinc finger protein 32), HNRNPA3P1 (heterogeneous nuclear ribonucleoprotein A3 pseudogene 1), CXCL12, THEM72 (transmembrane protein 72), RASSF4 (Ras association (RalGDS/AF-6) domain family member 4). (atlasgeneticsoncology.org)
  • These chemokine-modulated genes were further verified using quantitative RT-PCR and Western blot analysis. (biomedcentral.com)
  • Following removal of redundant and non-informative clones, seventeen mRNAs were found to be differentially expressed post treatment with either chemokine ligand with several representing known genes with established functions. (biomedcentral.com)
  • Twenty-one genes were upregulated in these transfected Jurkat cells following both CXCL12 and CXCL10, four genes displayed a discordant response and seven genes were downregulated upon treatment with either chemokine. (biomedcentral.com)
  • BCL2 and CXCL12 were key genes. (portlandpress.com)
  • Finally, the role of CXCR2 and CXCR4, their respective ligands CXCL1 and CXCL12, and the noncanonical dual agonist MIF in atheroprogression will be dissected. (ahajournals.org)
  • Using mouse genetics, we dissected the influence of IPC-derived CXCL12 on TCAs and interneurons by showing that Cxcl12 ablation in IPCs, leaving meningeal Cxcl12 intact, attenuates intracortical TCA growth and disrupts tangential interneuron migration in the subventricular zone. (ox.ac.uk)
  • We found ubiquitous CXCL12 distributions with local enrichments but no long-range gradients, in contrast to current assumptions about how CXCL12 controls migration of hematopoietic stem and progenitor cells (HSPCs) within BM. (nih.gov)
  • Some chemokines are considered pro- inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection , while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development . (wikipedia.org)
  • The major role of chemokines is to act as a chemoattractant to guide the migration of cells. (wikipedia.org)
  • A major rol of chemokines is to act as chemoattractants in guiding migration of cells. (wikipathways.org)
  • Over the past decade, functional studies of these molecules have revealed their importance for cell migration processes during embryogenesis, which, in addition to providing mechanistic insights into embryonic development, could complement information about chemokine function in the immune system. (biologists.org)
  • The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules. (nih.gov)
  • Overall, this chemokine system could be one of the key players of the neuro-immune interface that participates in shaping the brain in response to changes in the environment. (frontiersin.org)
  • Chemokines are a group of related chemoattractant peptides that are essential regulators of the immune system, both during homeostatic and inflammatory conditions. (mdpi.com)
  • While a function of chemokines is to regulate lymphocyte trafficking, the view that chemokines act simply as "chemotactic cytokines" has evolved to include the many critical roles they play in regulating innate and adaptive immune responses. (mdpi.com)
  • On one hand, the chemokine network is used by tumors to evade immune surveillance, resist apoptosis, and metastasize. (mdpi.com)
  • On the other hand, the chemokine system also plays a crucial role in the induction of antitumor immune responses and optimal effector function regulation of immune cells [ 1 , 4 , 5 ]. (mdpi.com)
  • Some chemokines control cells of the immune system during processes of immune surveillance, such as directing lymphocytes to the lymph nodes so they can screen for invasion of pathogens by interacting with antigen-presenting cells residing in these tissues. (wikipedia.org)
  • Chemotactic cytokines (chemokines) attract immune cells, although their original evolutionary role may relate more closely with embryonic development. (pnas.org)
  • Once at the site of injury, immune cells can react by releasing additional cytokines and chemokines, bringing more cells into the fold. (biolegend.com)
  • Due to the close link between HIV infection and drug abuse, an active area of research in the laboratory is the interaction of opiates with the endogenous chemokine system - a crucial regulator of both immune and nervous system function. (drexel.edu)
  • B) the multiple sequence alignment of the six CXCL12 isoforms. (atlasgeneticsoncology.org)
  • This protein binds CXCR4 and displays an exceptional degree of conservation (99 ) in mammals CXCL12 gamma is formed by a protein core shared by all CXCL12 isoforms, extended by a highly cationic carboxy-terminal (C-ter) domain that encompass four overlapped BBXB heparan sulfate (HS)-binding motifs. (monash.edu)
  • Three CXCL12 isoforms were synthesized for biologic characterization: CXCL12-1Cit, CXCL12-3Cit, and CXCL12-5Cit, in which Arg 8 , Arg 8 /Arg 12 /Arg 20 , or all five arginines were citrullinated, respectively. (jimmunol.org)
  • CXCL12 isoforms are generated by alternative splicing. (upstate.edu)
  • By both RT-PCR and immunohistochemistry, we mapped the localization of CXCL12 gamma both in mouse and human tissues, where it showed discrete differential expression. (monash.edu)
  • Homeostatic chemokines are constitutively expressed in particular organs or tissues. (biolegend.com)
  • Background and Purpose- The chemokine ligand CXCL12 is constitutively expressed in the bone marrow and other tissues including the brain endothelium and is responsible for regulating the trafficking of bone marrow progenitor cells. (ahajournals.org)
  • CXCL12 represents an element from the bone tissue marrow microenvironment secretome that's chiefly secreted in the bone tissue marrow from the MSCs [20]. (uitest.info)
  • Furthermore to its physiologic features of regulating hematopoietic progenitors homing towards the bone tissue marrow, and their retention inside the bone tissue marrow microenvironment, CXCL12 can be mixed up in proliferation, success as well as the metastases of several different malignancies [21, 22]. (uitest.info)
  • A series of investigations on ovarian neoplasms have improved our understanding of proinflammatory microenvironment including unfavorable cytokines, chemokines and imbalanced hormone production. (mdpi.com)
  • CXCL12 signaling has been shown to play an important role in the pathophysiology of CLL, especially in the interaction of leukemic cells with the tissue microenvironment. (pressebox.de)
  • In endothelial cells, mir-126 is also released with in these bodies are upon absorption in a neighbouring cell induce the CXCL12 dependant vascular protection. (wikipedia.org)
  • This family is defined by the location of the first two cysteine residues in the sequence, which are separated by one amino acid (C-X-C chemokine)(Hromas, 1997). (atlasgeneticsoncology.org)
  • Chemokines belong to a large group of structurally related and secretable, largely basic, chemotactic cytokines, which can be divided into 4 families (CC, CXC, CX 3 C, XC) based on the position of the first 2 cysteine residues. (ahajournals.org)
  • To date, >50 chemokines have been found, which can be divided into four families: CXC, CX3C, CC and XC, according to the different positions of the conserved N‑terminal cysteine residues. (spandidos-publications.com)
  • 50 chemokines have been identified, which can be divided into four families: CXC, CX3C, CC and XC, based on the different positions of the conserved N-terminal cysteine residues ( 9 ). (spandidos-publications.com)
  • All chemokines share a typical Greek key structure that is stabilised by disulphide bonds between conserved cysteine residues. (wikidoc.org)
  • Intramolecular disulphide bonds typically join the first to third, and the second to fourth cysteine residues, numbered as they appear in the protein sequence of the chemokine. (wikidoc.org)
  • The first two cysteines, in a chemokine, are situated close together near the N-terminal end of the mature protein, with the third cysteine residing in the centre of the molecule and the fourth close to the C-terminal end . (wikidoc.org)
  • Chemokines are classified according to their conserved N-terminal cysteine residues (C) that form the first disulfide bond. (aacrjournals.org)
  • Members of the chemokine family are divided into four groups depending on the location of their first two cysteine residues. (genscript.com)
  • The hematopoietic chemokine CXCL12 promotes integration of human endothelial colony forming cell-derived cells into immature vessel networks. (ox.ac.uk)
  • The CXCR4-CXCL12 axis regulates the hematopoietic stem cell niche-a property that has led to the approval of the CXCR4 antagonist plerixafor (AMD3100) for mobilization of hematopoietic precursors. (aacrjournals.org)
  • Recent studies have suggested a role for the chemokine CXCL12 in both de novo and acquired antiangiogenic resistance. (aacrjournals.org)
  • To study the role of CXCL12 (SDF-1) and its cleaved form SDF-1(5-67) in the trabecular cell viability. (arvojournals.org)
  • Since the role of chemokines in atherosclerotic vascular disease has been reviewed in this journal, significant progress has been accomplished in defining the regulation of chemokine expression and function in atherosclerosis. (ahajournals.org)
  • The considerable leap in insight over recent years leads us to anticipate further advances in comprehending the role of chemokines in atherosclerosis, allowing targeted interventions for its prevention and therapy. (ahajournals.org)
  • On the basis of our findings, it seems that the chemokines may play role in the pathogenesis of preterm labor. (hindawi.com)
  • CXCL12 plays a role in myofibroblast-mediated ECM remodeling in pathological conditions. (upstate.edu)
  • We study the role of CXCL12 in TM cell biology, and its function in mesenchymal stem cell engraftment for therapeutic TM remodeling. (upstate.edu)
  • Thus, CXCL12 plays a key role not only in endothelial cell sensing and guidance, but also in promoting the integration of ECFC-derived cells into developing vascular networks. (ox.ac.uk)
  • In this review, we summarized the role of CXCL12/CXCR4 in cancer, CXCR4 inhibitors under clinical study, and natural product CXCR4 antagonists. (bvsalud.org)
  • The exact role of these chemokines, their correlation with IL-6 after primary RRD, and their association with the future development of PVR are not yet known. (arvojournals.org)
  • Additional collaborative projects relate to the role of chemokines in cancer. (drexel.edu)
  • Chemokines play a fundamental role in the regulation of a variety of cellular, physiological, and developmental processes. (dovepress.com)
  • CXCL12 has been shown to play a significant role in animal models of ischemic stroke but its role in human stroke is unclear. (ahajournals.org)
  • NMR and fluorescence polarization measurements showed that the CXCR4 peptide stabilizes dimeric SDF-1alpha, and that sulfotyrosine 21 binds a specific site on the chemokine that includes arginine 47. (nih.gov)
  • Among other chemokines, CXCL12 has recently attracted much attention in the brain as it has been shown that it can be produced not only by glial cells but also by neurons. (frontiersin.org)
  • Analysis of protein levels revealed a similar stimulatory effect of a HFD on CXCL12 levels in the PVN and PFLH, as well as in blood, and an increase in the number of CXCR4-positive cells in the PVN. (frontiersin.org)
  • In the ARC, in contrast, levels of CXCL12 and number of CXCR4-positive cells were too low to measure. (frontiersin.org)
  • The CXCL12 protein was exclusively localized to Sertoli cells. (sigmaaldrich.com)
  • The antiviral potency of CXCL12-1Cit was reduced compared with CXCL12 and CXCL12-3Cit and CXCL12-5Cit (maximal dose 200 nM) could not inhibit infection of lymphocytic MT-4 cells with the HIV-1 strains NL4.3 and HE. (jimmunol.org)
  • Indeed, we detected CXCL12 in Sertoli cells of normal human testis, and relatively high expression in tumour stroma with concomitant weak staining in dispersed tumour cells. (edu.au)
  • Chemokines released by infected or damaged cells form a concentration gradient. (wikipedia.org)
  • Attracted cells move through the gradient towards the higher concentration of chemokine. (wikipedia.org)
  • Cells that are attracted by chemokines follow a signal of increasing chemokine concentration towards the source of the chemokine. (wikipedia.org)
  • Other chemokines are inflammatory and are released from a wide variety of cells in response to bacterial infection, viruses and agents that cause physical damage such as silica or the urate crystals that occur in gout . (wikipedia.org)
  • Bone marrow-derived cells and CXCL12 displayed a comparable efficacy on endometrial regeneration in mice with thin endometrium. (elsevier.com)
  • The defective engrafting activity of HSCs in S/G2/M was reversed when cells were allowed to progress into G1 prior to injection or when the hosts (but not the cells) were pretreated with a CXCL12 antagonist. (jci.org)
  • We have isolated and identified by differential display analysis 182 differentially expressed cDNAs from CXCR3-transfected Jurkat T cells following treatment with CXCL12 or CXCL10. (biomedcentral.com)
  • Peripheral blood CXCR5 + T cells also belong to the CD4 + memory T cell subset but, in contrast to tonsillar cells, are in a resting state and migrate weakly to chemokines. (rupress.org)
  • The outcome of these defensive mechanisms relies on the finely tuned traffic of T and B cells as well as antigen-presenting cells, suggesting that chemokines may be involved in the recruitment and proper positioning of leukocytes within these compartments. (rupress.org)
  • Attracted cells move toward areas of higher concentrations of the chemokine. (biolegend.com)
  • Upon sensing the inflammatory chemokine, cells will extravasate from the blood vessel and follow the gradient to its source. (biolegend.com)
  • Concurrently, CXCL12 2 diminished pulmonary implantation following tail vein injection of B16 melanoma cells ( 6 ). (aacrjournals.org)
  • 6 After ischemic stroke, CXCL12 mediates the inflammatory response by recruitment of neural progenitor cells and the mobilization of bone marrow-derived progenitor cells for tissue regeneration and neovascularization. (ahajournals.org)
  • We previously showed that CXCL12 binds to high- and low-affinity sites expressed by primary cells and cell lines, and forms complexes with CXCR4 as expected and also with a proteoglycan, syndecan-4, but does not form complexes with syndecan-1, syndecan-2, CD44 or beta-glycan. (semanticscholar.org)
  • Chemokines are small chemoattractant cytokines that are expressed in discrete anatomical locations. (aacrjournals.org)
  • Chemokines are 8-12 kDa peptides that function as chemoattractant cytokines and are involved in cell activation, differentiation, and trafficking. (dovepress.com)
  • Furthermore, the plasma CXCL12 levels from patients with CRC were also examined. (diva-portal.org)
  • Conclusions- Plasma CXCL12 levels may represent a novel biomarker of future ischemic stroke. (ahajournals.org)
  • The structural investigation of glycosaminoglycan binding to CXCL12 displays distinct interaction sites. (semanticscholar.org)
  • We hypothesize that this unusual domain could critically determine the biological properties of CXCL12 gamma through its interaction to, and regulation by extracellular glycosaminoglycans (GAG) and HS in particular. (monash.edu)
  • Interaction with CXCR4 was completely abolished for CXCL12-3Cit and CXCL12-5Cit. (jimmunol.org)
  • My subsequent work has convincingly shown that this chemokine-GAG interaction is essential for in vivo activity of these cytokines ( American Journal of Transplantation, 2010, 10:47-58, PNAS, 2012 ). (ncl.ac.uk)
  • Intermediate Progenitors Facilitate Intracortical Progression of Thalamocortical Axons and Interneurons through CXCL12 Chemokine Signaling. (ox.ac.uk)
  • We propose that CXCL12 signals from IPCs link cortical neurogenesis to the progression of TCAs and interneurons spatially and temporally. (ox.ac.uk)
  • The fundamental importance of chemokines for atherogenesis, progression, and destabilization of atherosclerotic plaques is now widely appreciated, but the degree of complexity, specificity, and cooperativity harnessed by these signal molecules to govern atherogenic cell recruitment and homeostasis is still being refined. (ahajournals.org)
  • They also suggest an ability of HSCs to express CXCL12 in a fashion that changes with cell cycle progression and is associated with a defective engraftment that can be overcome by in vivo administration of a CXCL12 antagonist. (jci.org)
  • They all also possess conserved amino acids that are important for creating their 3-dimensional or tertiary structure , such as (in most cases) four cysteines that interact with each other in pairs to create a Greek key shape that is a characteristic of chemokines. (wikidoc.org)
  • These structures provide new clues about the interactions between CXCR4 and its natural ligand CXCL12, and with the HIV-1 glycoprotein gp120. (sciencemag.org)
  • A 3D Tissue-wide Digital Imaging Pipeline for Quantitation of Secreted Molecules Shows Absence of CXCL12 Gradients in Bone Marrow. (nih.gov)
  • The Chemokine Cxcl12 And Regulation Of Hsc And Lymphocyte Development In The Bone Marrow Niche. (springer.com)
  • Chemokines are a superfamily of small molecule chemoattractive cytokines that regulate many cellular functions. (dovepress.com)
  • CXCL12 significantly promoted TC survival via its binding to CXCR4, whereas SDF-1(5-67) induced apoptosis in a dose-dependent manner via CXCR3 and caspase 3 activation. (arvojournals.org)
  • Proliferation rate and cell survival were not altered by CXCL12 in either seminoma (TCam-2) or non-seminoma (833ke) cell lines. (edu.au)
  • This function is shared by practically all members of the chemokine superfamily. (biologists.org)
  • Novel roles and regulatory factors: The lab has identified novel roles of chemokines in differentiated neurons, such as regulation of neuronal-glial communication, neurotransmission, and excitotoxicity. (drexel.edu)
  • What about the involvement of chemokines in the regulation of humoral responses? (rupress.org)