A classification of B-lymphocytes based on structurally or functionally different populations of cells.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
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.
The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES.
An encapsulated lymphatic organ through which venous blood filters.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.
A tumor necrosis factor superfamily member that plays a role in the regulation of B-LYMPHOCYTE survival. It occurs as a membrane-bound protein that is cleaved to release an biologically active soluble form with specificity to TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; B-CELL ACTIVATION FACTOR RECEPTOR; and B-CELL MATURATION ANTIGEN.
T-cell enhancement of the B-cell response to thymic-dependent antigens.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.
Ordered rearrangement of B-lymphocyte variable gene regions coding for the IMMUNOGLOBULIN CHAINS, thereby contributing to antibody diversity. It occurs during the differentiation of the IMMATURE B-LYMPHOCYTES.
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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156)
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A member of the tumor necrosis factor receptor superfamily that specifically binds B-CELL ACTIVATING FACTOR. It is found on B-LYMPHOCYTES and plays a role in maturation and survival of B-cells. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Membrane antigens associated with maturation stages of B-lymphocytes, often expressed in tumors of B-cell origin.
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
A lectin and cell adhesion molecule found in B-LYMPHOCYTES. It interacts with SIALIC ACIDS and mediates signaling from B-CELL ANTIGEN RECEPTORS.
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.
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.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
The class of heavy chains found in IMMUNOGLOBULIN M. They have a molecular weight of approximately 72 kDa and they contain about 57 amino acid residues arranged in five domains and have more oligosaccharide branches and a higher carbohydrate content than the heavy chains of IMMUNOGLOBULIN G.
Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES.
A member of the tumor necrosis factor receptor superfamily found on most T-LYMPHOCYTES. Activation of the receptor by CD70 ANTIGEN results in the increased proliferation of CD4-POSITIVE T-LYMPHOCYTES and CD8-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen.
Antigens which may directly stimulate B lymphocytes without the cooperation of T lymphocytes.
CXCR receptors isolated initially from BURKITT LYMPHOMA cells. CXCR5 receptors are expressed on mature, recirculating B-LYMPHOCYTES and are specific for CHEMOKINE CXCL13.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development.
Ordered rearrangement of B-lymphocyte variable gene regions coding for the kappa or lambda IMMUNOGLOBULIN LIGHT CHAINS, thereby contributing to antibody diversity. It occurs during the second stage of differentiation of the IMMATURE B-LYMPHOCYTES.
A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.
One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.
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.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.
Antibodies produced by a single clone of cells.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
Cells of the lymphoid series that can react with antigen to produce specific cell products called antibodies. Various cell subpopulations, often B-lymphocytes, can be defined, based on the different classes of immunoglobulins that they synthesize.
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.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties.
The number of LYMPHOCYTES per unit volume of BLOOD.
Established cell cultures that have the potential to propagate indefinitely.
Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.
A CXC chemokine that is chemotactic for B-LYMPHOCYTES. It has specificity for CXCR5 RECEPTORS.
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.
One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.
Reduction in the number of lymphocytes.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Substances that are recognized by the immune system and induce an immune reaction.
A transcription factor that is essential for CELL DIFFERENTIATION of B-LYMPHOCYTES. It functions both as a transcriptional activator and repressor to mediate B-cell commitment.
B-cells that have a role in regulating the immune response including the production of CYTOKINES. This function is in addition to their traditional role in making antibodies.
Glycoproteins found on the membrane or surface of cells.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
An enzyme that catalyzes the deamination of cytidine, forming uridine. EC
Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
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.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Benzene derivatives which are substituted with three nitro groups in any position.
A member of tumor necrosis factor superfamily found on MACROPHAGES; DENDRITIC CELLS and T-LYMPHOCYTES. It occurs as transmembrane protein that can be cleaved to release a secreted form that specifically binds to TRANSMEMBRANE ACTIVATOR AND CAML INTERACTOR PROTEIN; and B CELL MATURATION ANTIGEN.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.
Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.
A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.
An immunolglobulin light chain-like protein composed of an IMMUNOGLOBULIN VARIABLE REGION-like peptide (such as light chain like lambda5 peptide) and an IMMUNOGLOBULIN CONSTANT REGION-like peptide (such as Vpreb1 peptide). Surrogate light chains associate with MU IMMUNOGLOBULIN HEAVY CHAINS in place of a conventional immunoglobulin light chains to form pre-B cell receptors.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.
Mice bearing mutant genes which are phenotypically expressed in the animals.
A method to identify and enumerate cells that are synthesizing ANTIBODIES against ANTIGENS or HAPTENS conjugated to sheep RED BLOOD CELLS. The sheep red blood cells surrounding cells secreting antibody are lysed by added COMPLEMENT producing a clear zone of HEMOLYSIS. (From Illustrated Dictionary of Immunology, 3rd ed)
The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
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.
Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
Antibodies obtained from a single clone of cells grown in mice or rats.
Derivatives of phenylacetic acid. Included under this heading are a variety of acid forms, salts, esters, and amides that contain the benzeneacetic acid structure. Note that this class of compounds should not be confused with derivatives of phenyl acetate, which contain the PHENOL ester of ACETIC ACID.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
A tumor necrosis factor receptor superfamily member found expressed on peripheral B-LYMPHOCYTES. It has specificity for B-CELL MATURATION ANTIGEN and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 13.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A mouse substrain that is genetically predisposed to the development of systemic lupus erythematosus-like syndrome, which has been found to be clinically similar to the human disease. It has been determined that this mouse strain carries a mutation in the fas gene. Also, the MRL/lpr is a useful model to study behavioral and cognitive deficits found in autoimmune diseases and the efficacy of immunosuppressive agents.
A 15 kD "joining" peptide that forms one of the linkages between monomers of IMMUNOGLOBULIN A or IMMUNOGLOBULIN M in the formation of polymeric immunoglobulins. There is one J chain per one IgA dimer or one IgM pentamer. It is also involved in binding the polymeric immunoglobulins to POLYMERIC IMMUNOGLOBULIN RECEPTOR which is necessary for their transcytosis to the lumen. It is distinguished from the IMMUNOGLOBULIN JOINING REGION which is part of the IMMUNOGLOBULIN VARIABLE REGION of the immunoglobulin light and heavy chains.
Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.
The class of heavy chains found in IMMUNOGLOBULIN D. They have a molecular weight of approximately 64 kDa and they contain about 500 amino acid residues arranged in four domains and an oligosaccharide component covalently bound to the Fc fragment constant region.
Membrane proteins in precursor B-LYMPHOCYTES (pre-B Cells). They are composed of membrane-bound MU IMMUNOGLOBULIN HEAVY CHAINS in complex with SURROGATE LIGHT CHAINS instead of conventional IMMUNOGLOBULIN LIGHT CHAINS. Only successful rearrangement of the VDJ segments, at the Ig heavy chain gene locus (IMMUNOGLOBULIN HEAVY CHAIN GENES), will generate mu heavy chains that can pair with surrogate light chains. Thus formation of the pre-B cell receptors is an important checkpoint in the development of mature B cells.
A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Proteins isolated from the roots of the pokeweed, Phytolacca americana, that agglutinate some erythrocytes, stimulate mitosis and antibody synthesis in lymphocytes, and induce activation of plasma cells.
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.
The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.
A general term for various neoplastic diseases of the lymphoid tissue.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
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.
Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
A classification of lymphocytes based on structurally or functionally different populations of cells.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Lymphoid tissue on the mucosa of the small intestine.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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)
Heavy chains of IMMUNOGLOBULIN G having a molecular weight of approximately 51 kDa. They contain about 450 amino acid residues arranged in four domains and an oligosaccharide component covalently bound to the Fc fragment constant region. The gamma heavy chain subclasses (for example, gamma 1, gamma 2a, and gamma 2b) of the IMMUNOGLOBULIN G isotype subclasses (IgG1, IgG2A, and IgG2B) resemble each other more closely than the heavy chains of the other IMMUNOGLOBULIN ISOTYPES.
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.
A segment of the immunoglobulin heavy chains, encoded by the IMMUNOGLOBULIN HEAVY CHAIN GENES in the J segment where, during the maturation of B-LYMPHOCYTES; the gene segment for the variable region upstream is joined to a constant region gene segment downstream. The exact position of joining of the two gene segments is variable and contributes to ANTIBODY DIVERSITY. It is distinguished from the IMMUNOGLOBULIN J CHAINS; a separate polypeptide that serves as a linkage piece in polymeric IGA or IGM.
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.
A DNA-binding protein that represses GENETIC TRANSCRIPTION of target genes by recruiting HISTONE DEACETYLASES. Aberrant Blc-6 expression is associated with certain types of human B-CELL LYMPHOMA.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
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).
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
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 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.
Sites on an antigen that interact with specific antibodies.
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.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS.
A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.
Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
Antibody-mediated immune response. Humoral immunity is brought about by ANTIBODY FORMATION, resulting from TH2 CELLS activating B-LYMPHOCYTES, followed by COMPLEMENT ACTIVATION.
Progenitor cells from which all blood cells derive.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
A cytokine produced by bone marrow stromal cells that promotes the growth of B-LYMPHOCYTE precursors and is co-mitogenic with INTERLEUKIN-2 for mature T-LYMPHOCYTE activation.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
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.
Cell surface receptors for interleukin 21. They are heterodimeric proteins found on DENDRITIC CELLS and LYMPHOCYTES that consist of the INTERLEUKIN-21 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
A site located in the INTRONS at the 5' end of each constant region segment of a immunoglobulin heavy-chain gene where recombination (or rearrangement) occur during IMMUNOGLOBULIN CLASS SWITCHING. Ig switch regions are found on genes encoding all five classes (IMMUNOGLOBULIN ISOTYPES) of IMMUNOGLOBULIN HEAVY CHAINS.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Three regions (CDR1; CDR2 and CDR3) of amino acid sequence in the IMMUNOGLOBULIN VARIABLE REGION that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (RECEPTORS, ANTIGEN, T-CELL).
Substances that stimulate mitosis and lymphocyte transformation. They include not only substances associated with LECTINS, but also substances from streptococci (associated with streptolysin S) and from strains of alpha-toxin-producing staphylococci. (Stedman, 25th ed)
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Disorders characterized by proliferation of lymphoid tissue, general or unspecified.
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
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)
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
The class of heavy chains found in IMMUNOGLOBULIN A. They have a molecular weight of approximately 58 kDa and contain about 470 amino acid residues arranged in four domains and an oligosaccharide component bound covalently to their Fc fragment constant region.
An energy dependent process following the crosslinking of B CELL ANTIGEN RECEPTORS by multivalent ligands (bivalent anti-antibodies, LECTINS or ANTIGENS), on the B-cell surface. The crosslinked ligand-antigen receptor complexes collect in patches which flow to and aggregate at one pole of the cell to form a large mass - the cap. The caps may then be endocytosed or shed into the environment.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline.
The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the C-terminus half of the IMMUNOGLOBULIN FAB FRAGMENT and two or three of them make up the rest of the heavy chains (all of the IMMUNOGLOBULIN FC FRAGMENT)
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Infection with human herpesvirus 4 (HERPESVIRUS 4, HUMAN); which may facilitate the development of various lymphoproliferative disorders. These include BURKITT LYMPHOMA (African type), INFECTIOUS MONONUCLEOSIS, and oral hairy leukoplakia (LEUKOPLAKIA, HAIRY).
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.

TALL-1 is a novel member of the TNF family that is down-regulated by mitogens. (1/494)

Members of the tumor necrosis factor (TNF) family play important roles in modulation of immune responses. We describe the identification and cloning of a novel TNF family member that has been designated as TALL-1. TALL-1 is a 285-amino acid type II transmembrane protein. Its carboxy terminus shares approximately 35% sequence identity with the recently identified APRIL and approximately 20-25% with TNF, FasL, TRAIL, and lymphotoxin-alpha, suggesting that TALL-1 and APRIL belong to a subfamily of the TNF family of ligands. Northern blot analysis suggests that TALL-1 is expressed abundantly in peripheral blood leukocytes and weakly in spleen but is barely detectable in all other tissues examined. Reverse transcriptase-polymerase chain reaction analysis indicates that TALL-1 is specifically expressed in monocytes and macrophages but is undetectable in T and B lymphocytes. Furthermore, TALL-1 expression is dramatically down-regulated by phorbol myristate acetate/ionomycin.  (+info)

Identification and characterization of a novel cytokine, THANK, a TNF homologue that activates apoptosis, nuclear factor-kappaB, and c-Jun NH2-terminal kinase. (2/494)

By using the amino acid sequence motif of tumor necrosis factor (TNF), we searched the expressed sequence tag data base and identified a novel full-length cDNA encoding 285 amino acid residues and named it THANK. THANK is a type II transmembrane protein with 15-20% overall amino acid sequence homology to TNF, LT-alpha, FasL, and LIGHT, all members of the TNF family. The mRNA for THANK was expressed at high levels by peripheral blood leukocytes, lymph node, spleen, and thymus and at low levels by small intestine, pancreas, placenta, and lungs. THANK was also prominently expressed in hematopoietic cell lines. The recombinant purified protein expressed in the baculovirus system had an approximate molecular size 20 kDa with amino-terminal sequence of AVQGP. Treatment of human myeloid U937 cells with purified THANK activated nuclear transcription factor-kappaB (NF-kappaB) consisting of p50 and p65. Activation was time- and dose-dependent, beginning with as little as a 1 pM amount of the cytokines and as early as 15 min. Under the same conditions, THANK also activated c-jun NH2-terminal kinase (JNK) in U937 cells. THANK also strongly suppressed the growth of tumor cell lines and activated caspase-3. Although THANK had all the activities and potency of TNF, it did not bind to the TNF receptors. Thus our results indicate that THANK is a novel cytokine that belongs to the TNF family and activates apoptosis, NF-kappaB, and JNK through a distinct receptor.  (+info)

BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. (3/494)

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.  (+info)

BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. (4/494)

The tumor necrosis factor (TNF) superfamily of cytokines includes both soluble and membrane-bound proteins that regulate immune responses. A member of the human TNF family, BLyS (B lymphocyte stimulator), was identified that induced B cell proliferation and immunoglobulin secretion. BLyS expression on human monocytes could be up-regulated by interferon-gamma. Soluble BLyS functioned as a potent B cell growth factor in costimulation assays. Administration of soluble recombinant BLyS to mice disrupted splenic B and T cell zones and resulted in elevated serum immunoglobulin concentrations. The B cell tropism of BLyS is consistent with its receptor expression on B-lineage cells. The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation.  (+info)

Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. (5/494)

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti-DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.  (+info)

Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. (6/494)

TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TNF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupus-like changes in transgenic mice expressing TALL-1 under the control of a beta-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE. In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases.  (+info)

BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population. (7/494)

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor-triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.  (+info)

TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation. (8/494)

We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.  (+info)

Introduction A proliferation\inducing ligand (APRIL) and B cell activation factor (BAFF) are known to play a significant role in the pathogenesis of several diseases, including BAFF in malaria. mortality, has a wider geographic distribution and causes significant symptomatic disease 2. Currently, there is absolutely no obtainable vaccine to avoid malaria. Although sterile immunity against malaria parasite is most probably never achieved, people surviving in malaria\endemic areas may get a constant state of clinical immunity towards severe disease and loss of life. The mechanisms underlying the introduction of semi\immunity arent understood entirely. However, it really is more developed, that naturally acquired immunity against blood stage parasite involves both CD4+ T antibodies and cells 3. The need for antibodies was regarded in the research demonstrating that unaggressive transfer of serum Immunoglobulin G (IgG) from medically immune people into non\immune system recipients substantially ...
Objective: To assess the effects of tumour necrosis factor (TNF) antagonist therapy on B lymphocyte stimulator (BLyS) expression in patients with rheumatoid arthritis (RA).. Methods: Blood from 38 patients with RA from a single centre was collected prior to and following initiation of TNF antagonist therapy. Plasma BLyS protein levels, blood leukocyte BLyS mRNA levels and disease activity were longitudinally monitored. Twelve patients with RA who either refused or were felt not to be candidates for TNF antagonist therapy and five normal healthy volunteers served as TNF antagonist-naïve controls.. Results: Baseline plasma BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were elevated in patients with RA. Plasma BLyS protein levels declined following initiation of TNF antagonist therapy in good responders (GR) to TNF antagonist therapy but not in poor responders (PR). By contrast, the erythrocyte sedimentation rate (ESR) declined in response to TNF antagonist therapy in GR and PR. ...
Circulating endothelial progenitor cells (EPCs) are biologic markers of endothelial function. In patients with systemic lupus erythematosus (SLE), the numerical reduction and functional impairment of EPCs contribute to the endothelial dysfunction. Through ex vivo and in vitro studies, we aimed at evaluating the effects of B lymphocyte stimulator (BLyS) on EPC colonies and endothelial cells and also investigating BLyS receptor expression on these cells. EPCs were isolated from peripheral blood mononuclear cells (PBMC). In order to evaluate their ability to form colonies, EPCs were cultured on fibronectin-coated dishes and incubated with BlyS alone or BlyS and belimumab. Apoptosis of EPCs and endothelial cell line EA.hy926 was evaluated after 6, 12, and 24 h of incubation with BLyS and after 6 h with BLyS and belimumab. The expression of B cell activating factor-receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor
B cell-activating factor belonging to the TNF family (BAFF) and its receptor BAFF-R play critical roles in the maturation and survival of conventional peripheral B cells. However, they appeared to be dispensable for the generation and maintenance of CD5(+) B-1 cells as BAFF(-/-) and BAFF-R(-/-) mice have normal B-1 cell populations. Hence, it is presently unclear if B-1 cells are responsive to BAFF and if BAFF regulates some aspects of B-1 cell function. We show here that BAFF-R and transmembrane activator and CAML interactor (TACI) are the major receptors expressed by B-1 cells. Specifically, we show that BAFF treatment of B-1 cells leads to increased NF-kappaB p100 processing and CD21/CD35 expression. Interestingly, toll-like receptor (TLR) engagement of B-1 cells augmented the surface expression of BAFF receptors and rendered them responsive to BAFF costimulation, as evidenced by their increased proliferation, expression of cell surface activation markers and secretion of the pro-inflammatory
Introduction Blisibimod is a potent B cell-activating aspect (BAFF) antagonist that binds to both cell membrane-expressed and soluble BAFF. B cells reverted to baseline, resulting in a calculated 30 percent30 % decrease in total B cells by around 160 days following the 1st dosage. In both solitary- and multiple-dosing SC cohorts, the pharmacokinetic profile indicated sluggish absorption, dose-proportional publicity from 0.3 through 3.0 mg/kg SC and 1 through 6 mg/kg IV, linear pharmacokinetics over the dosage selection of 1.0C6.0 mg/kg, and accumulation ratios which range from 2.21 to 2.76. The comparative increase in memory space B cells had not been associated with security signals, as well as the 1192500-31-4 supplier occurrence of adverse occasions, anti-blisibimod antibodies, and medical laboratory abnormalities had been similar between blisibimod- and placebo-treated topics. Conclusions Blisibimod transformed the constituency from the B cell pool and solitary and multiple dosages of ...
Measure human BAFF/BLyS in cell culture supernates, serum, and plasma with our highly sensitive BAFF/BLyS/TNFSF13B Quantikine ELISA Kit.
B lymphocyte stimulator (BLyS) controls the proportion of transitional B cells completing differentiation and the longevity of most primary B cells. These key roles in B cell selection, survival and homeostasis make BLyS and its receptors attractive candidates for targeted B cell therapeutics. Here we have used a neutralizing hamster anti-mouse BLyS antibody to assess how BLyS depletion influences developing and primary B cell subsets, as well as how this treatment impacts primary TD and TI immune responses. Mice treated with 10F4 show rapid and substantial reductions in the transitional, follicular, and marginal zone pools which persist for ~40 days. In contrast, the only bone marrow subset affected is the mature recirculating B cell fraction. Interestingly, splenic B1 cells, but not peritoneal B1 cells, are reduced as well. Following the recovery of serum BLyS levels, peripheral reconstitution occurs gradually, such that normal B cell numbers return by day 70-80. Mice challenged with ...
The tumor necrosis family member BAFF is limiting for the survival of follicular B lymphocytes, but excessive BAFF signaling can lead to autoimmunity, suggesting that its activity must be tightly regulated. We have identified a conserved alternate splice isoform of BAFF, called deltaBAFF, which lacks 57 nt encoding the A-A1 loop and is co-expressed with BAFF in many mouse and human myeloid cells. Mouse deltaBAFF appears on the plasma membrane, but unlike BAFF it is inefficiently released by proteolysis. DeltaBAFF can associate with BAFF in heteromultimers and diminish BAFF bioactivity and release. Thus, alternative splicing of the BAFF gene suppresses BAFF B cell stimulatory function in several ways, and deltaBAFF may promote other functions as well ...
Naive peripheral B cells survive in vivo because of active stimulation by the TNF superfamily ligand B lymphocyte stimulator (BLyS/BAFF). Although the survival promoting properties of BLyS are well known, the signal pathways and molecular effectors that characterize this stimulation are still being elucidated. In this communication, we discuss the signal cascades that effect BLyS dependent survival and the regulation of BLyS induced signaling. We also examine the role of BLyS as a growth factor and propose that BLyS induced metabolic enhancement optimizes the B cell response to BCR and TLR-dependent signaling.
Given the recent success in the treatment of lupus patients with BAFF inhibitors, there is considerable interest in the lupus-like disease arising in BAFF-Tg mice. Taking advantage of the variability between 2 founder lines and gender differences in BAFF-Tg mice, we found that the tipping point for the manifestation of renal pathology and premature death was the level of BAFF protein in the serum. Slight increases in BAFF expression were sufficient to expand the B cell compartment size, yet high BAFF levels correlated with vastly increased serum IgA levels, glomerular IgA+ IC deposition, and kidney pathology. Furthermore, kidney function was improved when BAFF-Tg mice were crossed onto an IgA-deficient background. Interestingly, MRL/lpr mice with renal disease had 100-400 ng/ml BAFF in the blood (Supplemental Figure 1C), and, indeed, serum IgA levels were also elevated to about 1 mg/ml (data not shown). MRL/lpr mice are reported to have increased numbers of IgA-secreting cells, excess IgA ...
Mice were rendered specifically tolerant to the fluorescein isothiocyanatedextran (FITC) epitope by injection of FITC-dextran B512. Their spleen cells were removed at various times and cultivated in vitro with different polyclonal B-cell activators, such as lipopolysaccharide (LPS), purified protein derivative of tuberculin, and native dextran. LPS caused the appearance of high affinity anti-FITC plaque-forming cells to an equal extent with cells from untreated and tolerant animals, whereas native dextran failed to activate cells from tolerant mice, although it was a potent activator of normal cells. It was concluded that tolerance induction only affects those B cells that could respond to the polyclonal B-cell-activating properties of the tolerogen, but not other B cells having an identical set of Ig receptors directed against the tolerogen. ...
B lymphocyte stimulator (BLyS) is a factor determining the survival of B cells, and elevated levels in serum or locally have been observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients. Belimumab (LymphoStat-B), a human monoclonal antibody that inhibits BlyS, was developed for the treatment of these diseases. OBJECTIVE: To summarize preclinical development, efficacy and safety of belimumab in treatment of RA and SLE. METHODS: Articles found in a PubMed search and data presented in abstract form at international conferences up to August 2008 are described. RESULTS/CONCLUSIONS: Belimumab was well tolerated in treatment of RA over 24 weeks and SLE over 3 years. It significantly decreased rheumatoid factor (RF) levels, and modestly reduced symptoms of RA, especially in some subgroups such as patients with high disease activity, positive RF and no anti-TNF treatment experience. It also significantly reduced symptoms of SLE, and decreased anti-double-stranded DNA ...
Increased Ig, RF, and CIC levels in BAFF-Tg mice. (A) Reduced SDS-PAGE of sera from five control littermates and nine BAFF-Tg mice showing that BAFF increases I
The samples used in this paper were obtained from patients with osteoarthritis (OA) or RA during knee-TEP operations. First of all, expression of the known BAFF-binding receptors BCMA, TACI and BAFF-R was analyzed in SF of patients with OA and RA using flow cytometry and immunohistochemistry. In a further step, the influence of several stimulants, including cytokines, TLR-agonists and cell activators on receptor expression was tested. Finally, taking into account BAFF function in other cell types, SF were stimulated with BAFF and stained with Annexin V in order to analyze its effect on apoptosis in SF ...
BAFF/BLyS, a member of the tumor necrosis family (TNF) superfamily of ligands, is a crucial survival factor for B cells. BAFF binds three receptors, TACI, BCMA, and BR3, with signaling through BR3 being essential for promoting B cell function. Typical TNF receptor (TNFR) family members bind their cognate ligands through interactions with two cysteine-rich domains (CRDs). However, the extracellular domain (ECD) of BR3 consists of only a partial CRD, with cysteine spacing distinct from other modules described previously. Herein, we report the solution structure of the BR3 ECD. A core region of only 19 residues adopts a stable structure in solution. The BR3 fold is analogous to the first half of a canonical TNFR CRD but is stabilized by an additional noncanonical disulfide bond. BAFF-binding determinants were identified by shotgun alanine-scanning mutagenesis of the BR3 ECD expressed on phage. Several of the key BAFF-binding residues are presented from a beta-turn that we have shown previously to ...
CD257 (BAFF, BLyS), APC, clone: 1D6, eBioscience™ 25 Tests; APC CD257 (BAFF, BLyS), APC, clone: 1D6, eBioscience™ Primary Antibodies CD251 to CD400
D to neuronal cultures. Blocking BAFF-R ligation with TACI-Ig inhibited wild-type, but not Baffrm/m, neuronal survival in a dose-dependent manner (Fig. 3 C).
BAFF belongs to the tumor necrosis factor (TNF) family, and its downstream signaling plays a critical role in B-cell survival and maturation.
WASHINGTON and LONDON, November 16, 2016 /PRNewswire/ -- GSKs Benlysta® (belimumab) Shows Sustained Benefits in Patients with SLE.
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BLyS Human Recombinant fused to His tag at N-terminus produced in E.Coli is a single, non-glycosylated polypeptide chain containing 190 amino acids and having a molecular mass of 21 kDa.
Welcome to the REBOOT StudyThe REBOOT study will test whether a combination of two different drugs, belimumab (Benlysta®) and ri
TY - JOUR. T1 - BAFF expression correlates with idiopathic inflammatory myopathy disease activity measures and autoantibodies. AU - López De Padilla, Consuelo M.. AU - McNallan, Kelly T.. AU - Crowson, Cynthia S.. AU - Bilgic, Hatice. AU - Bram, Richard J.. AU - Hein, Molly S.. AU - Ytterberg, Steven R.. AU - Amin, Shreyasee. AU - Peterson, Erik J.. AU - Baechler, Emily C.. AU - Reed, Ann M.. PY - 2013/3/1. Y1 - 2013/3/1. N2 - Objective. To investigate B cell survival cytokine messenger RNA (mRNA) levels as biomarkers of idiopathic inflammatory myopathies (IIM). Methods. We measured and compared mRNA levels of B cell survival cytokines by quantitative real-time polymerase chain reaction in 98 patients with IIM, 38 patients with systemic lupus erythematosus, and 21 healthy controls. The cytokines were B cell-activating factor belonging to the tumor necrosis factor family (BAFF);ΔBAFF; and a proliferation-inducing ligand (APRIL); and their receptors BAFF-R, transmembrane activator and calcium ...
Background The TNF superfamily member B lymphocyte stimulator (BLyS), referred to as BAFF, is known to be an effective modulator of peripheral B cell homeostasis that promotes B cell survival and differentiation. BLyS is expressed by a few stromal cells, T cells, and most myeloid cell. BLyS transgenic mice show an expansion of the peripheral mature B cell compartment, hyperglobulinemia, anti-single-stranded DNA and anti-double-stranded DNA antibodies, and circulating immune complexes. A proliferation-inducing ligand (APRIL) is a homolog to BLyS that is expressed by monocytes, macrophages, DCs, T cells, and others. APRIL is virtually undetectable in normal tissues but is strongly expressed in adenocarcinomas and can accelerate the growth of malignant cells in vitro and in vivo. APRIL/BLyS heterotrimers are present in the serum of patients with systemic autoimmune diseases like rheumatoid arthritis (RA), SLE, and SS. APRIL over expression promotes a strong survival signal for both CD4+ and CD8+ T ...
B cell maturation starts in the bone marrow but is completed in the spleen (Hardy et al., 2007). Survival of IgM+ splenic B cells is linked to the antiapoptotic B cell lymphoma 2 (BCL2) family of proteins and their opposing proapoptotic antagonist, BCL2-interacting mediator of cell death (BIM; Enders et al., 2003), and depends on tonic signals from surface IgM and IgD B cell antigen receptors transmitted through spleen tyrosine kinase (SYK), Brutons tyrosine kinase (BTK), and phosphatidylinositol 3 kinase (Srinivasan et al., 2009). Starting from the transitional 2 (T2) stage, B cells also depend on survival signals provided by a circulating cytokine, B cell-activating factor (BAFF), engaging the BAFF receptor (BAFFR; Khan, 2009). BCRs and BAFFR signal via pathways that activate transcription factors of the NF-κB family, and these play essential roles in mediating survival of B cells (Siebenlist et al., 2005).. CD74, also called MHC II invariant chain or Ii, is a type 2 transmembrane protein ...
BAFF receptor (BAFF = B cell-activating factor of the TNF family) is a main pro-survival receptor expressed by human B cells. BAFFR deficiency is caused by a homologous deletion within the BAFFR gene...
Abstract: Autoimmunity is traditionally attributed to altered lymphoid cell selection and/or tolerance, whereas the contribution of innate immune cells is less well understood. Autoimmunity is also associated with increased levels of B cell-activating factor of the TNF family (BAFF; also known as B lymphocyte stimulator), a cytokine that promotes survival of self-reactive B cell clones. We describe an important role for myeloid cells in autoimmune disease progression. Using Lyn-deficient mice, we show that overproduction of BAFF by hyperactive myeloid cells contributes to inflammation and autoimmunity in part by acting directly on T cells to induce the release of IFN-. Genetic deletion of IFN- or reduction of BAFF activity, achieved by either reducing myeloid cell hyperproduction or by treating with an anti-BAFF monoclonal antibody, reduced disease development in lyn-/- mice. The increased production of IFN- in lyn-/- mice feeds back on the myeloid cells to further stimulate BAFF release. ...
Results: Salivary BAFF levels (median: 12.39 ng/ml) were significantly decreased by using HQ both at 12 (2.78 ng/ml, P = 0.008) and 24 weeks (0.54 ng/ml, P = 0.011). Similarly, decreases in serum BAFF levels (5.23 ng/ml) were seen at 12 and 24 weeks after HQ treatment (2.18 ng/ml, P = 0.008 and 0.0 ng/ml, P = 0.012, respectively). Serum and salivary BAFF levels were significantly lower in healthy controls (0.37 ng/ml and 0.0 ng/ml, resp.) compared to those of pSS before HQ therapy (P = 0.006 and P = 0.001, resp.). Unstimulated salivary flows were similar in patients treated with HQ after 12 (0.38 ml/min) and 24 weeks (0.50 ml/min) (P = 0.51) but higher than the patients rate at baseline (0.04 ml/min) (P = 0.008 ...
The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fcγ receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab. Eleven patients presented with LON. Fifty non-LON control subjects were matched by diagnosis, age, sex, and treatments. Single-nucleotide polymorphisms of FCGR (FCGR2A 131H/R, FCGR2B 232I/T, FCGR3A 158V/F) and BAFF promoter polymorphism −871C/T were analyzed with polymerase chain reaction-based techniques, and serum immunoglobulin M (IgM) and BAFF levels were analyzed by enzyme-linked immunosorbent assay. Flare-free survival was related to LON occurrence and
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In our previous study, overexpression of extracellular proteinase inhibitor (Expi) gene accelerated apoptosis of mammary epithelial cells, and induced expression of B cell activating factor (BAFF) gene. In this study, we found induction of BAFF-receptor (BAFF-R) gene expression in the Expi-transfected cells. A proliferation-inducing ligand (APRIL) gene is another TNF family member and the closest known relative of BAFF. We found induction of APRIL gene expression in the Expi-overexpressed apoptotic cells. NF-B gene was also induced in the Expi-overexpressed cells. Expression patterns of BAFF and APRIL pathway-related genes were examined in in vivo mouse mammary gland at various reproductive stages. Expression levels of BAFF gene were very low at early pregnancy, increased from mid-pregnancy, and peaked at lactation, and thereafter decreased at involution stages of mammary gland. Expression of BAFF-R gene was highly induced in involution stages compared to lactation stages. Thus, expression ...
The monoclonal antibody 11C1 reacts with the B cell-activating factor receptor (BAFF-R), also known as BAFF receptor 3 (BR3) or CD268. It is a 19 kDa type III transmembrane protein which belongs to the TNF receptor superfamily and is mainly expressed on B cells. BAFF-R plays an important role in B cell differentiation and promotes survival and activation of B cells. - Belgique
Belimumab (also known as Benlysta™) is currently being studied in Phase III clinical trials to determine whether or not it is effective for lupus. Belimumab specifically reduces the actions of a protein called B lymphocyte stimulator, or BLyS. BLyS is a protein that increases the lifespan and inflammatory potential of certain immune cells called B cells, which are known to be hyperactive in lupus patients. Belimumab, which interferes with BLyS, is a human antibody. This means that it looks a lot like the antibodies that the immune system makes to fight off viruses. But in this case, belimumab targets only the protein BLyS. Because it only has one target, it is called a monoclonal antibody ...
Follicular B cell survival requires signaling from BAFFR, a receptor for BAFF and the B cell antigen receptor (BCR). This tonic BCR survival signal is distinct from that induced by antigen binding and may be ligand-independent. We show that inducible inactivation of the Syk tyrosine kinase, a key signal transducer from the BCR following antigen binding, resulted in the death of most follicular B cells because Syk-deficient cells were unable to survive in response to BAFF. Genetic rescue studies demonstrated that Syk transduces BAFFR survival signals via ERK and PI3 kinase. Surprisingly, BAFFR signaling directly induced phosphorylation of both Syk and the BCR-associated Igα signaling subunit, and this Syk phosphorylation required the BCR. We conclude that the BCR and Igα may be required for B cell survival because they function as adaptor proteins in a BAFFR signaling pathway leading to activation of Syk, demonstrating previously unrecognized crosstalk between the two receptors. ...
Background B cell activating factor (BAFF) plays an important role in the differentiation, survival and activation of B cells rheumatoid arthritis (RA). BAFF receptor (BAFFR) is a crucial receptor for the survival of mature B cells in developing B cells. Paeoniflorin-6-O-benzene sulfonate (CP-25) exerted its anti-inflammatory effects through regulating immune cells responses. The study was to investigate the regulatory effect of CP-25 on BAFF/BAFFR-nuclear factor of kappa B (NFkapaB) signaling in B cell of collagen induced-arthritis (CIA) mice.Methods Mice CIA was induced by injection of type II collagen. Arthritis index (AI) and swollen joint count (SJC) were assessed, spleen and joints histopathology were observed.B cells subsets, BAFF receptor were analyzed by flow cytometry. BAFF and immunoglobulin (Ig) levels were measured by protein antibody array. The expressions of TRAF2, MKK3, MKK6, p-P38, and p-NFkapaB65 in NF-kapaB signaling were analyzed by western blot ...
Results SLEDAI-2K (median baseline score: 8.0; IQR: 4.0-13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health (p,0.0001 for all). SDI scores remained stable (p=0.08). Patients with baseline SDI scores,1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208-0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025-0.427). In contrast, baseline BLyS levels≥1.2 ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222-5.387). ...
Belimumab is a human monoclonal antibody that selectively targets B-lymphocyte stimulator an important factor in the survival of B cells.
Background: Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulating protein, was the first biologic agent approved for, and the first drug approved in 55 years for, the treatment of systemic lupus erythematosus (SLE) by the US Food and Drug Administration (FDA). Objective: This article reviews the current research on belimumab and provides recommendations on its use in the treatment of SLE. Methods: The Cochrane Library, EBSCO, IPA, MEDLINE, and SCOPUS were searched for research published from January 2000 to November 2011, using the search terms belimumab, Benlysta, and Lympho-Stat B. Selection criteria included peer-reviewed original research articles on the pharmacology, pharmacokinetic properties, drug interactions, and clinical efficacy and tolerability of belimumab in the treatment of SLE. Abstracts from the annual meetings of major rheumatology medical organizations and societies were searched and reviewed for new content. Additional information on belimumab was obtained from the
vessels, giving the hystologic picture of leukocytoclastic vasculitis. Clinically, this inflammation is manifested as arthralgias, fatigue, and lesions mainly in skin, kidneys and peripheral nerves, however, any organ system can be involved. Most of the so far reported clinical and laboratory investigations deal with mixed CG in chronic hepatitis C virus (HCV) infection while the data concerning essential CG vasculitis (CV) are scarce. Only recently, so-called noninfectious CV has attracted more attention of the medical community. Chronic antigenic stimulation, increased cytokine and growth factor (BLyS) levels and complement activation may are implicated in the pathogenesis of CV, etiology of which remains largely unknown. Objectives: To investigate clinical and imunoserologic characteristics of patients with CG and their relation to presence and clinical manifestations of vasculitis, as well as to the etiology of CG; explore quantitative and qualitative characteristics of cryoG; to analyze a ...
The cumulative prednisone dose over 52 weeks also was lower in the belimumab group, at a median of 4,190 mg, compared with the placebo group, at 4,758.1 mg (P=0.0005). This study builds on findings from previous studies, which suggest that belimumab has a corticosteroid-sparing effect, they noted.. With regard to safety, the overall rate of adverse events was similar in the belimumab and placebo groups, and while the incidence rate of serious adverse events was higher in the placebo group (18.3% versus 12.3%), the rate of infectious serious adverse events was similar (5.3% and 5.5%).. The investigators also considered adverse events of special interest, including malignancies, post-infusion systemic reactions, depression/suicide/self injury, and deaths, finding similar rates between the belimumab and placebo groups. In the belimumab group, there were no suicide attempts or completed suicides, although there was one case of suicidal ideation. In the placebo group, there was one suicide ...
Belimumab 10 mg/kg IV plus oral azathioprine 2 mg/kg/day; belimumab administered on Days 0, 14, 28, and then every 28 days until the end of the study. If the results in the double-blind period show that belimumab is safe and effective, then participants have the option to continue treatment with belimumab in a 6-month open-label extension phase. Patients who opt to participate in the extension will continue to receive belimumab 10 mg/kg IV every 28 plus oral azathioprine 2 mg/kg/day days for an additional 6 months ...
Recent studies suggest an association between chronic inflammation, modulating the tissue microenvironment, and tumor biology. Tumor environment consists of tumor, stromal and endothelial cells and infiltrating macrophages, T lymphocytes, and dendritic cells, producing an array of cytokines, chemokines and growth factors, accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of tumor and surrounding cells, responsible for tumor progression and spreading or induction of antitumor immune responses and rejection. Tumor Necrosis Factor (TNF) family members (19 ligands and 29 receptors) represent a pleiotropic family of agents, related to a plethora of cellular events from proliferation and differentiation to apoptosis and tumor reduction. Among these members, BAFF and APRIL (CD257 and CD256 respectively) gained an increased interest, in view of their role in cell protection, differentiation and growth, in a number of lymphocyte, epithelial and
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The cytokine BAFF is produced by a number of cell types, including monocytes, neutrophils, macrophages, dendritic cells, and some subsets of T cells (17). Receptors for BAFF, however, were initially thought to be restricted to more differentiated B-lineage cells. Therefore, the expression of BAFF receptors on transformed B-lineage lymphocytes in CLL was not entirely unexpected. In contrast, based on BAFF-null and BAFF-R-null mutants as well as other studies, it has been generally accepted that precursor B-lineage cells do not express this receptor. Our studies confirm that there is no expression of this receptor in normal bone marrow pre-B cells. Interestingly, Rodig and colleagues (35) also performed FACS on two pre-B ALL samples and reported that these were negative for expression of BAFF-R. Therefore, the prominent expression of the BAFF-R that we detected on both Ph-positive and Ph-negative ALL samples was unanticipated. In fact, all 12 samples that were tested by us, including original ALL ...
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Recombinant Mouse BAFF (carrier-free) - BAFF is a TNF cytokine member (a type II membrane protein) that acts in both a membrane-bound form and soluble cytokine form.
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APRIL, a member of the TNF superfamily, is expressed in monocytes, macrophages, certain transformed cell lines, certain cancers of the colon, and lymphoid tissues. APRIL, along with another TNF family member, BAFF, competes for two receptors, TACI and BCM
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  • p38 mitogen-activated protein kinase was activated by HSA and was involved in NF-κB-dependent transcription of fractalkine. (asnjournals.org)
  • Using cell lines isolated from MCF+FIR populations, we found that the elevated NF-κB activity was correlated with enhanced clonogenic survival, and increased NF-κB subunit p65 levels were associated with a decrease in phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK in all radioresistant MCF+FIR cell lines. (aacrjournals.org)
  • Mitogen‐activated protein kinase (MAPK) modules, composed of three protein kinases activated by successive phosphorylation, are involved in the signal transduction of a wide range of extracellular agents. (embopress.org)
  • Mitogen‐activated protein kinase (MAPK) modules are involved in the signal transduction of a wide variety of signals in all eukaryotic organisms. (embopress.org)
  • Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1. (semanticscholar.org)
  • p38 Mitogen-activated protein kinase mediates hypoxia-induced vascular endothelial growth factor release in human endothelial cells. (docphin.com)
  • Human umbilical vein endothelial cell lines (ECV304) were cultured in normoxic or hypoxic conditions for 12 approximately 24 h and harvested for determination of VEGF mRNA expression and phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (p38 MAPK) by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. (docphin.com)
  • Phagocytosis of apoptotic cells (efferocytosis) induces macrophage differentiation towards a regulatory phenotype (IL-10 high /IL-12p40 low ). (hindawi.com)
  • The present study revealed that PQQ induces the activation (tyrosine autophosphorylation) of epidermal growth factor receptor (EGFR) and its downstream signaling in a ligand-independent manner, leading to increased cellular proliferation in an epithelial cell line A431. (sigmaaldrich.com)
  • Integrin signaling also induces formation of a complex of p130Cas, the adapter protein Crk, and a third molecule, DOCK 180, that is required for membrane ruffling, a component of cell migration ( 13 , 14 ). (jimmunol.org)
  • Finally, antisense-mediated knockdown of Stat3 induces apoptosis in EGFR mutant lung cancer cells. (aacrjournals.org)
  • H 2 O 2 induces a time- and dose-dependent activation of NFAT3 transcription factor. (physiology.org)
  • Our study demonstrates that PL induces quiescent cartilage cell activation and proliferation leading to new cartilage formation, identifies PL activated pathways playing a role in these processes, and provides a rationale to the application of PL for therapeutic treatment of damaged articular cartilage. (deepdyve.com)
  • This lymphokine is produced by T helper cells (TH) and induces activated CTLp to proliferate and differentiate. (ubc.ca)
  • Our findings that PA transactivates EGFR and induces NOX activity in vascular smooth muscle cells provide new insights into molecular mechanisms of PA's role in cancer and Refsum disease. (biomedcentral.com)
  • The Tpl-2 protooncoprotein activates the nuclear factor of activated T cells and induces interleukin 2 expression in T cell lines. (semanticscholar.org)
  • As(3+) potently induces Mt1 mRNA expression in mouse hepa1c1c7 cells. (cdc.gov)
  • This partially purified BCAF induces Ia expression, cell size increase and proliferation of small resting B cells. (pasteur.fr)
  • The inhibition of TNF-α production by the anti-folate drugs does not seem to be a result of (apoptotic) cell death of T cells whereas SSZ induces apoptosis of T cells (data not shown). (biomedcentral.com)
  • Ulevitch, R. J. and Ye, R. D. (1995) Platelet-activating factor induces NF-kappa B activation through a G protein-coupled pathway. (springer.com)
  • A chemical released by cancer cells that induces motility, enabling the cells to metastasize. (thefreedictionary.com)
  • Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. (lenus.ie)
  • We also tested whether either HSP 60 induces nuclear factor-κB (NF-κB), which contributes to the gene expression of these molecules. (jci.org)
  • We find that stimulation with exogenous IL-4 or CD40-cross-linking induces B cell expression of CD120b, but not CD120a. (docphin.com)
  • Vascular endothelial growth factor (VEGF) has been recognized as an angiogenic factor that induces endothelial proliferation and vascular permeability. (elsevier.com)
  • It has been also shown to play an important role in the proliferation and differentiation of B cells. (wikipedia.org)
  • B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation. (nih.gov)
  • When co-cultured with CD14(+) myeloid cells and/or B-cell activating factor (BAFF), a cytokine produced by activated myeloid cells, there was a significant increase in CpG-specific B cell proliferation, and the number of large B cells in general or positive for CD25, all of which are markers for B cell activation. (nih.gov)
  • Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). (rcsb.org)
  • Pyrroloquinoline quinone stimulates epithelial cell proliferation by activating epidermal growth factor receptor through redox cycling. (sigmaaldrich.com)
  • The intracellular redox state regulates the EGFR signaling through the redox-sensitive catalytic cysteine of PTP1B and modulates cell proliferation. (sigmaaldrich.com)
  • Our data suggest that PQQ may stimulate epithelial cell proliferation by activating EGFR by oxidation and subsequent inactivation of PTP1B via its redox cycling. (sigmaaldrich.com)
  • However, the role of cdk3 in cell proliferation, as well as cell transformation, is not yet clearly understood. (aacrjournals.org)
  • Results also indicated that siRNA directed against cdk3 (si-cdk3) suppresses ATF1 activity, resulting in inhibition of proliferation and growth of human glioblastoma T98G cells in soft agar. (aacrjournals.org)
  • These results clearly showed that the cdk3-ATF1 signaling axis is critical for cell proliferation and transformation. (aacrjournals.org)
  • Cdk4 kinase activity was shown to be required for proliferation of breast cancer cells and mammary tumorigenesis in cdk4-null mice ( 9 , 10 ) and kinase-deficient cyclin D1 knock-in mice ( 11 ). (aacrjournals.org)
  • Knockdown of cdk2 was shown to inhibit proliferation and colony formation of human melanoma cells ( 14 ), and ablation of cdk2 decreased Ras/cdk4-dependent malignant progression in mouse skin tumorigenesis models ( 15 ). (aacrjournals.org)
  • Ectopic overexpression of cdk3, but not cdk2, enhanced the proliferation and anchorage-independent growth of Ratl cells, which was associated with activation of Myc ( 17 ). (aacrjournals.org)
  • However, although cdk3 might have an effect on cell proliferation and transformation, the precise role of cdk3 in carcinogenesis has not been clearly elucidated. (aacrjournals.org)
  • Pre-B ALL cells depend on bone marrow stroma for in vitro proliferation and survival ( 4 , 5 ). (aacrjournals.org)
  • Angel P, Karin M (1991) The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. (springer.com)
  • In this study, we analyzed extracts of the sponge Cribrochalina vasculum for their ability to inhibit tumor cell proliferation. (aacrjournals.org)
  • Vascular smooth muscle cells (SMCs) can undergo phenotypic modulation, 1 a process by which a quiescent, contractile SMC alters its expression profile to facilitate cell proliferation, migration, or inflammatory cell recruitment (see reviews 1 , 2 ). (ahajournals.org)
  • Platelet lysate activates quiescent cell proliferation and reprogramming in human articular. (deepdyve.com)
  • In a cartilage permissive culture environment, differentiated cells also resumed proliferation after exposure to PL. These findings correlated with an up‐regulation of the proliferation/survival pathways ERKs and Akt and with an induction of cyclin D1. (deepdyve.com)
  • These events were possibly related to the cell proliferation because the HIF‐1 inhibitor acriflavine inhibited HIF‐1 binding to HIF‐1 responsive elements and cell proliferation. (deepdyve.com)
  • The importance of BAFF to B cells was confirmed when mice transfected with the gene BAFF manifested excessive lymphocytic proliferation, together with autoantibody production ( 4 ). (aaccjnls.org)
  • 8-NH 2 -Ado treatment inhibited cell proliferation, activated cell death, and did not activate transcription of the p53 target gene p21 or increase protein levels of either p53 or p21. (aacrjournals.org)
  • MEF2 belongs to the MADS-box super family and is a class of key transcriptional regulators that positively regulate cell differentiation, cell proliferation, morphogenesis, cell survival, and apoptosis [ 1 , 2 ]. (aging-us.com)
  • Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. (mdpi.com)
  • In response to injury, epithelial cells initiate a programmed series of separate yet interdependent responses, such as proliferation, migration, and matrix assembly, to rapidly restore the integrity of damaged tissue. (rupress.org)
  • The effects of miR-144 were evaluated by cell proliferation, migration, transwell, and tumorigenicity assays. (biomedcentral.com)
  • Our results showed that miR-144 was reduced in CCA tissues and suggested that miR-144 may be an essential suppresser of CCA cell proliferation and invasion through targeting LIS1. (biomedcentral.com)
  • Production occurred in the absence of proliferation and did not require the addition of accessory cells or IL-2. (sdu.dk)
  • B-cell survival depends on signals induced by B-cell activating factor (BAFF) binding to its receptor (BAFF-R). In mice, mutations in BAFF or BAFF-R cause B-cell lymphopenia and antibody deficiency. (pnas.org)
  • B-lymphocyte survival is maintained by tonic signaling of the B-cell antigen receptor complex ( 1 ) and by signals induced after binding of the cytokine BAFF/BLYS to the BAFF-receptor (BAFF-R), a member of the TNF receptor superfamily ( 2 ). (pnas.org)
  • Although bovine blood-derived CD21(+) B cells express TLR9 and proliferate in response to CpG in mixed-cell populations, purified bovine B cells do not proliferate significantly in response to CpG ODN, even when the B cell receptor is engaged. (nih.gov)
  • Recently, it has been found that mycoplasmal lipoproteins and lipopeptides are capable for leading to apoptoic cell death in macrophage through toll-like receptor 2 (TLR2) and TLR6 [ 13 , 14 ]. (hindawi.com)
  • When expressed in cells, an engineered form of NFAT1 unable to interact with AP-1 transcription factors diminished T cell receptor (TCR) signaling, increased the expression of inhibitory cell surface receptors, and interfered with the ability of CD8(+) T cells to protect against Listeria infection and attenuate tumor growth in vivo. (nih.gov)
  • CD36 is involved in the recognition of apoptotic cells (AC), and we have shown that the platelet-activating factor receptor (PAFR) is also involved. (hindawi.com)
  • The addition of apoptotic cells to a subtumorigenic dose of melanoma cells promoted tumour growth, and this phenomenon was significantly reduced when an antagonist of the PAF receptor (PAFR) was injected into the tumour site [ 7 ]. (hindawi.com)
  • Both agents diminished the release of [14C]arachidonate from these prelabeled cells in response to PAF in a dose-dependent fashion, though not decreasing release in response to AII or A23187, indicating that they blocked the effect of PAF on phospholipase activation, consistent with receptor blocking activity. (aspetjournals.org)
  • We recently reported that the particulate matter from urban air simulates platelet-activating factor receptor (PAFR)-dependent adhesion of pneumococci to airway cells. (bmj.com)
  • Cigarette smoke extract stimulates platelet-activating factor receptor (PAFR)-dependent pneumococcal adhesion to lower airway cells. (bmj.com)
  • The three known receptors for BAFF on B cells include BCMA (B-cell maturation antigen), TACI (transmembrane activator, calcium modulator, and cyclophilin ligand interactor), and BAFF-R/BR3 (BAFF receptor/BLyS receptor 3). (aacrjournals.org)
  • In agreement with the proposed lack of significance of this receptor/cytokine for early B-cell development, mice lacking BAFF-R or BAFF have normal pro- and pre-B-cell compartments ( 18 , 19 ). (aacrjournals.org)
  • However, the expression of both BAFF and its receptor BAFF-R in leukemias and lymphomas involving more mature B-lineage cells prompted us to examine a possible role of BAFF and its receptors in ALL. (aacrjournals.org)
  • 1 One prominent inflammatory pathway responsive to angiotensin receptor ligation culminates in the translocation of nuclear factor-κ light chain enhancer of activated B cells (NF-κB) to the nucleus where it drives transcription of a broad array of inflammatory mediators. (ahajournals.org)
  • For example, basal expression of the proinflammatory protein protease-activated receptor 1 (PAR-1) is transcriptionally regulated by NFATc1 in human saphenous vein SMCs. (ahajournals.org)
  • We evaluated Stat3 activation in early stage non-small cell lung cancers (NSCLC) and how this relates to upstream epidermal growth factor receptor (EGFR) activation, tumor apoptosis, and prognosis. (aacrjournals.org)
  • High-density tissue microarrays using tissues from 176 surgically resected NSCLC were evaluated for expression of phosphorylated Stat3 (pStat3) and epidermal growth factor receptor (pEGFR) along with tumor apoptosis. (aacrjournals.org)
  • The epidermal growth factor receptor (EGFR) is frequently overexpressed in NSCLC and can regulate NSCLC growth and survival. (aacrjournals.org)
  • Angiotensin II (ANG II), an end product of the renin-angiotensin system, is an eight-amino acid peptide that can bind to its receptor, AT1 or AT2, on the surface of cells. (physiology.org)
  • implies that, in addition to TNF-induced cascades, T cell receptor (TCR)-mediated signal transduction pathways could also be affected. (aspetjournals.org)
  • T lymphocytes direct specific immune functions by antigen recognition via the T cell receptor complex. (aspetjournals.org)
  • We have previously identified a novel complex between the platelet-derived growth factor (PDGF)β receptor and the sphingosine 1-phosphate receptor-1 (S1P1). (strath.ac.uk)
  • Third, SB649146 blocked the S1P-induced activation of p42/p44 MAPK in airway smooth muscle cells, a response that is mediated by the S1P1 receptor. (strath.ac.uk)
  • We now report that inverse agonism of the S1P1 receptor with SB649146 reduced the endocytosis of the PDGFβ receptor-S1P1 receptor complex and the stimulation of p42/p44 MAPK and cell migration in response to PDGF. (strath.ac.uk)
  • These findings are the first to report that a GPCR inverse-agonist reduces growth factor-induced receptor tyrosine kinase signaling, fundamentally broadening their mechanism of action. (strath.ac.uk)
  • The data obtained with SB649146 also suggest that the constitutively active endogenous S1P1 receptor enhances PDGFinduced cell migration. (strath.ac.uk)
  • Toll-like receptor (TLR) expression and TLR‑mediated interleukin-8 production by human submandibular gland epithelial cells. (semanticscholar.org)
  • Thus, receptor occupancy on B cells by BAFF ( 14 ), its urinary excretion in case of renal failure ( 13 ), and sequestration within immune complexes ( 15 ) all hinder assessment of BAFF. (aaccjnls.org)
  • PAF exerts its function upon binding to its specific receptor, PAF receptor (PAFR), which is abundantly expressed in leukocytes and endothelial cells (ECs). (frontiersin.org)
  • PAF activates a G protein-coupled receptor named PAF receptor (PAFR) ( 5 - 7 ), which results in pleiotropic and potent biological effects including platelet activation, airway constriction, hypotension, and increased vascular permeability via signaling pathways such as phosphatidylinositol 3-kinase (PI3K), PKC, phospholipase A2 (PLA 2 ), and PLC ( 5 , 8 - 10 ). (frontiersin.org)
  • TNF-α activates c-Jun N-terminal kinase (JNK) to phosphorylate and suppress the activity of insulin receptor (IR) substrate 1 ( 4 ). (diabetesjournals.org)
  • The factor increases the frequency of IL-2 receptor expressing cells within a population, thereby increasing the response to IL-2. (ubc.ca)
  • To explore molecular mechanisms of phytanic acid-induced cellular pathology, we investigated its effect on NADPH oxidase (NOX) and epidermal growth factor receptor (EGFR) in rat aortic smooth muscle cells (RASMC). (biomedcentral.com)
  • Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. (semanticscholar.org)
  • This occurred in the estrogen receptor-positive (ER+) MCF-7 cells that express wild-type p53, the ER+ T47-D cells that express mutant p53, and the ER− MDA-MB-468 cells or MDA-MB-231 cells that both express mutant p53. (aacrjournals.org)
  • PAF stimulation of NF-κB activation and transcription of immediate-early genes have been investigated in peripheral blood mononuclear cells and in transfected Chinese hamster ovary cells expressing the cloned PAF receptor. (springer.com)
  • Ito, K. and Shimizu, T. (1994) Transfected platelet-activating factor receptor activates mitogen-activated protein (MAP) Kinase and MAP kinase Kinase in Chinese hamster ovary cells. (springer.com)
  • NRP1 partially mediates EBV-activated EGFR/RAS/ERK signalling, and NRP1-dependent receptor tyrosine kinase (RTK) signalling promotes EBV infection. (nature.com)
  • In addition, NRP1 mediates the penetration of iRGD conjugated nanoparticles into tissue and cells through functioning as a receptor for CendR motif, the proteolytic cleavage products of iRGD after binding to integrins 17 , 20 . (nature.com)
  • Protein tyrosine kinases are subdivided into the cytosolic nonreceptor family and the transmembrane growth factor receptor family, which includes receptors for insulin and insulin-like growth factor (IGF-1). (jneurosci.org)
  • The receptor tyrosine kinase ERBB4, a member of the epidermal growth factor receptor (EGFR) family, is unusual in that ERBB4 can undergo intramembrane proteolysis, releasing a soluble intracellular domain (ICD) that modulates transcription in the nucleus. (sciencemag.org)
  • These observations connect the unusual nuclear function of a growth factor receptor with a mechanosensory pathway and suggest that NRG1-ERBB4-YAP signaling contributes to the aggressive behavior of tumor cells. (sciencemag.org)
  • ERBB4 (also known as HER4) is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases (RTKs). (sciencemag.org)
  • Mouse small intestine tissue showed that c-Kit, stem cell factor (SCF), and glial cell-derived neurotrophic factor (GDNF) mRNA expression levels were significantly higher in the LF-CQPC03 treated mice than in control mice, while transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels were significantly lower in the LF-CQPC03 treated mice than in control mice. (mdpi.com)
  • Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells. (lenus.ie)
  • Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. (lenus.ie)
  • In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. (lenus.ie)
  • The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. (lenus.ie)
  • We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. (lenus.ie)
  • Collectively, this study supports a novel function for factor Xa as an endogenous, receptor-associated protein-sensitive, protease-activated receptor 2-dependent regulator of myeloid cell pro-inflammatory cytokine production. (lenus.ie)
  • Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration, and invasion of breast cancer cells. (lenus.ie)
  • Platelet derived growth factor receptor (PDGFR) is a membrane tyrosine-kinase receptor required for fibroblast activation in stromal proliferations. (elsevier.com)
  • The phenotypic changes effected by TNF-alpha can be recapitulated by crosslinking CD120b (p75 TNF-receptor), but not CD120a (p55 TNF-receptor), with mAbs presented on Fc gamma RII (CD32)-expressing L cells. (docphin.com)
  • A recent report has revealed that peroxisome proliferator-activated receptor-γ (PPARγ) is expressed not only in adipocytes but also in monocytes/macrophages and has suggested that PPARγ may have a role in the differentiation of monocytes/macrophages. (elsevier.com)
  • When individual cells of the L3T4 (CD4)+ F23.1+ T cell clone E9.D4 were transferred by micromanipulation into wells coated with the monoclonal anti-T cell receptor antibody F23.1, up to 90% of cells produced CSF as detected by CSF-dependent hemopoietic cell lines. (sdu.dk)
  • Kelso, A & Owens, T 1988, ' Production of two hemopoietic growth factors is differentially regulated in single T lymphocytes activated with an anti-T cell receptor antibody ', Journal of Immunology , bind 140, nr. 4, s. 1159-67. (sdu.dk)
  • This study was designed to investigate the molecular mechanisms responsible for the induction of proinflammatory cytokines gene expression and apoptosis in human monocytic cell line THP-1 stimulated by lipoproteins (LPs) prepared from Mycoplasma genitalium . (hindawi.com)
  • Cell apoptosis was also detected by Annexin V-FITC-propidium iodide (PI) staining and acridine orange (AO)-ethidium bromide (EB) staining. (hindawi.com)
  • LPs were also found to increase the DNA-binding activity of NF- B, a possible mechanism for the induction of cytokine mRNA expression and the cell apoptosis. (hindawi.com)
  • genitalium -derived LP may be an important etiological factor of certain diseases due to the ability of LP to produce proinflammatory cytokines and induction of apoptosis, which is probably mediated through the activation of NF- B. (hindawi.com)
  • With the intimate interaction with the host cells, LP could influence the functions of monocytes, macrophages, and brain astrocytes, then lead to proinflammatory cytokine production or, in particular cases, to necrosis or apoptosis [ 11 ]. (hindawi.com)
  • NF- κ B activation may have a two-fold influence on cell apoptosis, either inhibiting apoptosis or accelerating cell death, which depends on different cell lines and different stimuli. (hindawi.com)
  • and we have studied whether M. genitalium LP could induce human monocytes cell line THP-1 to express proinflammatory cytokines and apoptosis. (hindawi.com)
  • Given the expression of NF-κB in leukemic, but not normal primitive cells, the hypothesis that inhibition of NF-κB might induce leukemia-specific apoptosis was tested by treating primary cells with the proteasome inhibitor MG-132, a well-known inhibitor of NF-κB. (bloodjournal.org)
  • If LSCs use unique mechanisms to control processes such as apoptosis, then it may be possible to target such pathways as a means to specifically destroy leukemic, but not normal hematopoietic cells. (bloodjournal.org)
  • Several studies have shown that malignant B cells from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma B, and multiple myeloma express abnormal levels of B-cell-activating factor (BAFF), which protects these cells from spontaneous or drug-induced apoptosis ( 12 - 14 ). (aacrjournals.org)
  • Chang MC et al (2001) Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. (springer.com)
  • e) INS832/13 cells were treated with glucose or palmitate, and apoptosis was determined by ELISA analysis of DNA fragments at 24 h after treatment. (asm.org)
  • In this report, we describe several lines of evidence supporting a role of ATF3 in stress-induced beta-cell apoptosis. (garvan.org.au)
  • Taken together, our results suggest ATF3 to be a novel regulator of stress-induced beta-cell apoptosis. (garvan.org.au)
  • Early-stage NSCLC tumors have activated EGFR-Stat3 signaling with low apoptosis. (aacrjournals.org)
  • Cell lines harboring mutant EGFR molecules are dependent on EGFR for survival because inhibition of EGFR using gefitinib, RNA interference knockdown, or EGFR antibodies results in apoptosis ( 12 - 14 ). (aacrjournals.org)
  • Stat3 regulates a number of pathways important in tumorigenesis, including cell cycle progression, apoptosis, tumor angiogenesis, invasion and metastasis, and tumor cell evasion of the immune system ( 15 , 17 , 18 ). (aacrjournals.org)
  • One critical role of Stat3 is protecting cells against apoptosis through the transcriptional up-regulation of survival genes, such as Bcl-xL, Bcl-2, Mcl-1 , and survivin ( 19 - 22 ). (aacrjournals.org)
  • Because of the important role of Stat3 in tumor growth and survival, we evaluated activated Stat3 signaling in early-stage NSCLC tumors and correlated activated Stat3 with clinical characteristics as well as upstream EGFR signaling and tumor cell apoptosis. (aacrjournals.org)
  • However, NFATc1 and NFATc2 also bind to numerous other promoters, such as the Fas ligand promoter ( 4 , 8 ), and therefore also control apoptosis and further important processes in the life cycle of a T cell ( 12 , 15 ). (asm.org)
  • The upregulation of ANRIL facilitated invasion of hypoxic osteosarcoma cells and inhibited cell apoptosis. (springermedizin.de)
  • Idel and co-workers [ 12 ] have reported that supraphysiological levels of phytanic acid induce nitric oxide-mediated apoptosis in cultured vascular smooth muscle cells suggesting thereby that phytanic acid might have a role in regulation of cell growth in vivo. (biomedcentral.com)
  • Though nitric oxide has recently been implicated in phytanic acid-induced apoptosis of smooth muscle cells, any role of reactive oxygen species such as highly reactive superoxide anion production in relation to phytanic acid-mediated regulation of vascular growth remains to be examined. (biomedcentral.com)
  • 8-NH 2 -Ado induced apoptotic death of MCF-7 cells and apoptosis was not inhibited by knockdown of functional p53. (aacrjournals.org)
  • MEF2A is one of the members of the MEF2 family and participates in various cellular processes, including muscle development, neuronal differentiation, cell-growth control, and apoptosis, in the form of homodimers or heterodimers [ 3 ]. (aging-us.com)
  • 3 4 In addition, when the overlying epithelium is damaged or infected, corneal stromal cells rapidly undergo apoptosis, effectively precluding any fibrotic response. (arvojournals.org)
  • abstract = "A method has been developed to measure the production by single activated T lymphocytes of two hemopoietic growth factors, granulocyte-macrophage CSF (GM-CSF) and multipotential CSF (multi-CSF or IL-3). (sdu.dk)
  • abstract = "IntroductionHypoxia can stimulate 18F-fluorodeoxyglucose (FDG) uptake in cultured cells. (elsevier.com)
  • BAFF is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. (wikipedia.org)
  • This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFF-R. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. (wikipedia.org)
  • There was also a parallel expression of the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, as well as the cytokine tumor necrosis factor-alpha. (nih.gov)
  • The aim of this study was to investigate the effects of a proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), on the invasive properties of epithelial cells constitutively expressing activated Ras or Src. (nih.gov)
  • Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. (rcsb.org)
  • Both BAFF and the related cytokine APRIL bind to TACI and BCMA, whereas only BAFF binds to BAFF-R. The BAFF-R/BR3 pathway in particular is crucial to the differentiation of late primary B cells and survival of mature B cells ( 19 , 20 ). (aacrjournals.org)
  • The cytokine transforming growth factor β1 (TGF-β1) is secreted in a latent form that has no known biological activity. (portlandpress.com)
  • Originally identified as key components linking cytokine signals to transcriptional events in cells, STAT proteins, especially Stat3 and Stat5, play a major role in tumorigenesis ( 15 ). (aacrjournals.org)
  • Methods]: Primary and immortalized microglial cells were stimulated by sPLA2-IIA in order to characterize the cytokine-like actions of the phospholipase. (csic.es)
  • Moreover, barbiturates suppressed the expression of a luciferase reporter gene under control of NFAT (stably transfected Jurkat T cells), and of the cytokine genes interleukin-2 and interferon-γ that contain functional binding motifs for NFAT within their regulatory promotor domains (human peripheral blood CD3 + lymphocytes). (aspetjournals.org)
  • Neutrophil migration across monolayers of cytokine-prestimulated endothelial cells: a role for platelet-activating factor and IL-8. (rupress.org)
  • In a previous study we observed that neutrophils respond with a rapid rise in [Ca2+]i during adherence to cytokine-activated endothelial cells (EC), caused by EC membrane-associated platelet-activating factor (PAF). (rupress.org)
  • A murine anti-IL-8 antiserum was found to also partially inhibit the neutrophil transmigration across cytokine-activated EC. (rupress.org)
  • Our results indicate that human neutrophils are activated and guided by EC-associated PAF and EC-derived IL-8 during the in vitro diapedesis in between cytokine-stimulated EC. (rupress.org)
  • This cytokine may be expressed in and secreted by salivary gland epithelial cells (SGEC) after stimulation with type I IFN or viral or synthetic dsRNA. (semanticscholar.org)
  • Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine that plays a central role in obesity-induced insulin resistance. (diabetesjournals.org)
  • Tumor necrosis factor-α (TNF-α) is a cytokine that plays significant roles in multiple cellular processes. (diabetesjournals.org)
  • TNF-α also provokes activation of the transcription factor nuclear factor- κB, which causes the expression of genes like tyrosine phosphatase-1B and suppression of cytokine signaling proteins to antagonize the insulin signaling ( 7 , 8 ). (diabetesjournals.org)
  • We treated BMs with LPS and dapsone, and the treated cells underwent cellular activity assay, flow cytometry analysis, cytokine production assessment, and reactive oxygen species assay. (vetsci.org)
  • In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. (lenus.ie)
  • We examined the expression of adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), and the production of the proinflammatory cytokine interleukin-6 (IL-6). (jci.org)
  • In this study, we demonstrate that nuclear factor (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines. (jimmunol.org)
  • NFATc2 is part of the NFAT family of transcription factors. (atlasgeneticsoncology.org)
  • Another, highly conserved region of the NFAT family is the DNA binding domain that is structurally related to the DNA binding domain of the Rel -Family of transcription factors. (atlasgeneticsoncology.org)
  • Activating transcription factor 3 (ATF3) is a stress-inducible gene and encodes a member of the ATF/CREB family of transcription factors. (garvan.org.au)
  • Objective- Calcineurin (Cn) and the nuclear factor of activated T cells (NFAT) family of transcription factors are critical in vascular smooth muscle cell (SMC) development and pathology. (ahajournals.org)
  • Cn, a cytosolic, calcium-dependent phosphatase, activates the NFAT family of transcription factors (NFATc1-c4) for nuclear translocation and subsequent target gene transcription. (ahajournals.org)
  • In mammalian cells, two transcription factors, XBP1 and ATF6, activate ER stress-responsive genes. (plantcell.org)
  • Signal transducers and activators of transcription 3 (Stat3), a member of the STAT family of transcription factors, regulates multiple oncogenic pathways, including pathways regulating tumor cell survival. (aacrjournals.org)
  • We tested the hypothesis that bradykinin could elicit long-lasting changes in nociceptor function by activating members of the nuclear factor of activated T-cells (NFAT) family of transcription factors. (aspetjournals.org)
  • Activation of several transcription factors, including the nuclear factor of activated T cells-3 (NFAT3), contributes in part to the changes in gene expression associated with hypertrophy ( 28 , 29 ). (physiology.org)
  • NFAT3 belongs to the NFAT family of transcription factors, discovered as important regulators of immune responses in mammals ( 8 , 25 , 38 ). (physiology.org)
  • The four genuine members of the family of nuclear factor of activated T-cell transcription factors (NFAT), NFATc1, NFATc2, NFATc3, and NFATc4, share a conserved DNA binding domain of approximately 300 amino acids, the Rel similarity domain. (asm.org)
  • Treatment of primary CD3 + lymphocytes with barbiturates inhibited the PMA and ionomycin induced increase in DNA binding of NFAT, whereas the activity of other transcription factors, such as Oct-1, SP-1, or the cAMP response element-binding protein, remained unaffected. (aspetjournals.org)
  • These transcription factors are phosphorylated in the cytosol of resting T cells. (aspetjournals.org)
  • The gene expression profiles of ABC DLBCLs were notable for the high expression of target genes of the nuclear factor (NF)-κB transcription factors, raising the possibility that constitutive activity of the NF-κB pathway may contribute to the poor prognosis of these patients. (rupress.org)
  • The Rel/nuclear factor (NF) * -κB transcription factors integrate diverse intracellular signaling pathways that are activated during normal cellular differentiation and during immune responses ( 1 - 4 ). (rupress.org)
  • The transcription of viral genes in HPV-16 is partially controlled by a number of cellular transcription factors. (microbiologyresearch.org)
  • We show that PEF-1 and Sp1 are distinct transcription factors: they recognize different DNA sequences, have different electrophoretic mobilities and different glycosylation patterns. (microbiologyresearch.org)
  • Although this group may include a few cases of BTK deficiency ( 12 ), most B-lymphopenic patients have unknown defects, some of which may affect genes regulating early B-cell development and/or B-cell survival ( 13 ). (pnas.org)
  • Signaling by TLR2 leads to an activation of nuclear transcription factor NF- κ B and an induction of NF- κ B-controlled genes such as Bcl-Xs, Bax, and Bad after its activation [ 15 ]. (hindawi.com)
  • We defined the genomic regions occupied by endogenous and engineered NFAT1 in primary CD8(+) T cells and showed that genes directly induced by the engineered NFAT1 overlapped with genes expressed in exhausted CD8(+) T cells in vivo. (nih.gov)
  • For example, we have recently shown that primitive AML cells aberrantly express the tumor suppressor genes IRF1 (interferon regulatory factor 1) and DAPK (death-associated protein kinase). (bloodjournal.org)
  • Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites. (jimmunol.org)
  • Methods and Results- Genome-wide expression arrays were used to identify genes both (1) differentially activated in response to PDGF-BB and (2) whose differential expression was reduced by both the Cn inhibitor cyclosporin A and the NFAT inhibitor A-285222. (ahajournals.org)
  • Stat3 forms dimers when activated by tyrosine kinase signals and translocates to the nucleus to regulate expression of genes by binding to elements within promoters ( 16 ). (aacrjournals.org)
  • Due to the binding of NFATc1 and NFATc2 to the promoters of the gamma interferon (IFN-γ), IL-4, and IL-5 genes (i.e., the promoters of genes that are active either in Th1 or in Th2 cells), it has been assumed that NFATc1 and NFATc2 play an important role in driving naive T cells to effector Th1 and Th2 cells. (asm.org)
  • Like many other proinflammatory genes, MCP-1 and RANTES genes are controlled by the transcription factor nuclear factor κB (NF-κB) ( 8 ). (asnjournals.org)
  • Activated calcineurin dephosphorylates NFAT, allowing it to translocate to the nucleus and to bind response elements of genes critical for lymphocyte activation and regulation of immune function. (aspetjournals.org)
  • TNFα), growth factors (e.g., granulocyte macrophage-colony-stimulating factor), and pro-apoptotic genes (e.g. (aspetjournals.org)
  • It is generally believed that the final decision for cell death or survival after irradiation is made based on the profile of IR-inducible genes (refs. (aacrjournals.org)
  • Nuclear factor-κB (NF-κB), a stress-sensitive heterodimeric transcription factor in the regulation of the stress-responsive genes, has been shown to initiate the prosurvival signaling pathways ( 18 - 20 ). (aacrjournals.org)
  • For instance, NF-κB activates many genes involved in inflammation, cell transformation, and antiapoptotic responses ( 24 , 25 ), suggesting that both prosurvival and antisurvival pathways can be induced by NF-κB activation. (aacrjournals.org)
  • Upon phosphorylation by the IκB kinase (IKK) complex, IκBα is targeted for ubiquitination and proteasomal degradation, and released NF-κB dimers can translocate to the nucleus and activate transcription of target genes ( 3 ). (rupress.org)
  • Finally, exogenous PAF treatment increases cell permeability and upregulates the expression of genes coding for proteins involved in leukocyte adhesion to the endothelium in primary chicken endothelial cells (chAEC). (frontiersin.org)
  • As a very important transcription factor, MEF2A has an essential DNA-binding site in the MyoDa gene-control region and can activate many muscle-specific, growth factor-induced, and stress-induced genes [ 4 , 5 ]. (aging-us.com)
  • We identify host cell genes and pathways relevant for infection by combining three different computational approaches: gene and pathway overdispersion analysis, prediction of cell-state transition probabilities, as well as future cell states. (nature.com)
  • The depth of data and using unspliced messenger RNA (mRNA) as a predictor for future cell states allows us to connect the course of infection to the activity of specific host cell genes and pathways. (nature.com)
  • Overexpressing ERBB4 in cultured mammary epithelial cells or adding the ERBB4 ligand neuregulin 1 (NRG1) to breast cancer cell cultures promoted the expression of genes regulated by YAP, such as CTGF . (sciencemag.org)
  • Melatonin modulates TLR4-mediated inflammatory genes through MyD88- and TRIF-dependent signaling pathways in lipopolysaccharide-stimulated RAW264.7 cells. (lenus.ie)
  • The effect of nerve growth factor (NGF) on the expression of neurofilament and Thy-1 genes in rat PC12 pheochromocytoma cells was examined at both the transcriptional and post-transcriptional levels. (royalholloway.ac.uk)
  • This is the first molecular evidence for the reversible activation of neuron-specific genes during NGF-induced differentiation in PC12 cells. (royalholloway.ac.uk)
  • BAFF, the only ligand of BAFF-R, is secreted by cells of nonhematopoietic as well as of hematopoietic origin, including monocytes, macrophages, neutrophils, and activated B cells ( 2 , 4 ). (pnas.org)
  • Clearance of apoptotic cells (AC) by macrophages, also called efferocytosis, plays a central role in tissue homeostasis, and the impaired clearance of altered cells has been associated with the development of autoimmune and chronic inflammatory diseases [ 1 ]. (hindawi.com)
  • M1 or classically activated macrophages are induced by the recognition of PAMPs (pathogen associated molecular patterns) and by proinflammatory cytokines. (hindawi.com)
  • the alternatively activated macrophages are induced by Th2 cytokines, and the regulatory macrophages are induced by anti-inflammatory cytokines, immune complexes, apoptotic cells, and oxidised lipids, among other stimuli [ 2 , 3 ]. (hindawi.com)
  • 4 ]. The authors showed that the addition of apoptotic cells to macrophages inhibited the expression of proinflammatory cytokines induced by LPS. (hindawi.com)
  • In this regard, the hypertensive bone marrow chimeras lacking Bcl10 on somatic cells have reduced cardiac accumulation of macrophages and T lymphocytes, both of which can promote tissue fibrosis. (ahajournals.org)
  • Proteinuria over time is also associated with a remarkable increase in NF-κB activity in proximal tubular cells, paralleled by upregulation of renal MCP-1 mRNA, heralding the local accumulation of monocytes, macrophages, and T cells ( 13 ). (asnjournals.org)
  • The resulting T-cell hybridoma constitutively produced a lymphokine that activated murine macrophages to the tumoricidal state without the concomitant production of migration inhibition factor, colony-stimulating factor, or interferon. (elsevier.com)
  • We tested the hypothesis that chlamydial or human HSP 60 activates human endothelial cells (ECs), smooth muscle cells (SMCs), and monocyte-derived macrophages. (jci.org)
  • We have reported that VEGF is remarkably expressed in activated macrophages, endothelial cells, and smooth muscle cells within human coronary atherosclerotic lesions, and we have proposed the significance of VEGF in the progression of atherosclerosis. (elsevier.com)
  • In conclusion, Ox-LDL upregulates VEGF expression in macrophages and endothelial cells, at least in part, through the activation of PPARγ. (elsevier.com)
  • Inhibition of the IKK/NF-κB pathway in mouse or human leukemia cells blocked the capacity of BAFF to induce c-MYC or promote leukemia-cell survival and significantly impaired disease progression in Myc/Baff Tg mice. (pnas.org)
  • Similarly, when cells were infected with the recombinant adenovirus expressing dominant negative mutant of the IkB kinase 2, a 55% inhibition of fractalkine mRNA was achieved. (asnjournals.org)
  • NF-κB plays a central role in the regulation of the immune system and several previously reported effects of barbiturates on the function of immune cells could be explained by inhibition of NF-κB. (aspetjournals.org)
  • DNA content analysis showed that NF-κB inhibition caused both cell death and G1-phase growth arrest. (rupress.org)
  • Inhibition of MDA-MB-231 cell autophagy, by reduction of ATG7 or 3-methyladenine treatment, did not block this 8-NH 2 -Ado-mediated cytotoxicity. (aacrjournals.org)
  • Previously we have shown that adhesiveness of endothelial cells for mesenchymal stem cells correlates with the inhibition of mitochondrial function of endothelial cells and secretion of von Willebrand factor. (biomedcentral.com)
  • Inhibition of p38 MAPK, but not ERK-1,2, in endothelial cells completely abrogated the stimulation of the mesenchymal stem cell adhesion by von Willebrand factor. (biomedcentral.com)
  • Because the transporter can be rapidly activated by coapplication of IGF-1 and an Src kinase and can be deactivated by membrane-permeable protein tyrosine kinase inhibitors, we suggest that activation of K + /Cl − cotransporter function by endogenous protein tyrosine kinases mediates the developmental switch of GABAergic responses to hyperpolarizing inhibition. (jneurosci.org)
  • Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. (lenus.ie)
  • Interaction between BAFF and BAFF-R activates classical and noncanonical NF-κB signaling pathways. (wikipedia.org)
  • The Ras and Rho families of small GTPases control a diverse set of biochemical pathways in lymphoid cells. (jimmunol.org)
  • Second, induction of ATF3 is mediated in part by the NF-kappaB and Jun N-terminal kinase/stress-activated protein kinase signaling pathways, two stress-induced pathways implicated in both type 1 and type 2 diabetes. (garvan.org.au)
  • Importantly, mutant EGFR proteins selectively activate Akt and signal transducers and activators of transcription (STAT) pathways that are important in NSCLC cell survival ( 12 , 13 ). (aacrjournals.org)
  • Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways. (semanticscholar.org)
  • Gemcitabine activates DNA damage pathways that signal to the tumor suppressor p53 ( 1 ), and a functional p53 pathway improves gemcitabine cytotoxicity ( 2 ). (aacrjournals.org)
  • Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. (lenus.ie)
  • B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFSF13B gene. (wikipedia.org)
  • BAFF steady-state concentrations depend on B cells and also on the expression of BAFF-binding receptors. (wikipedia.org)
  • BAFF is the natural ligand of three unusual tumor necrosis factor receptors named BAFF-R (BR3), TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), and BCMA (B-cell maturation antigen), all of which have differing binding affinities for it. (wikipedia.org)
  • BAFF-R is involved in the positive regulation during B cell development. (wikipedia.org)
  • Inadequate level of BAFF will fail to activate B cells to produce enough immunoglobulin and will lead to immunodeficiency. (wikipedia.org)
  • Increased levels of BAFF may initiate alloreactive B cell and T cell immunity, therefore may promote allograft rejection. (wikipedia.org)
  • Analyzing BAFF-R expression and BAFF-binding to B cells in common variable immunodeficiency (CVID) patients, we identified two siblings carrying a homozygous deletion in the BAFF-R gene. (pnas.org)
  • Without BAFF-R, B-cell development is arrested at the stage of transitional B cells and the numbers of all subsequent B-cell stages are severely reduced. (pnas.org)
  • They also did not mount a T-independent immune response against pneumococcal cell wall polysaccharides but only one BAFF-R-deficient sibling developed recurrent infections. (pnas.org)
  • In BAFF-R-deficient mice, B cells develop normally up to the stage of IgM + immature/transitional B cells but cannot complete maturation in the spleen, as BAFF/BAFF-R-dependent survival signals are missing ( 5 - 8 ). (pnas.org)
  • Searching for genetic defects affecting B-cell homeostasis, we identified two related individuals carrying the same homozygous deletion within the TNFRSF13C gene removing part of the BAFF-R transmembrane region. (pnas.org)
  • Human BAFF-R deficiency strongly impairs the development and homeostasis of follicular, IgM memory/marginal zone, and class-switched memory B cells. (pnas.org)
  • BAFF serum levels were analyzed in 14 patients with less than 3% B cells, BAFF-R surface expression in 40 additional patients and BAFF binding to B cells in 18 additional patients, respectively. (pnas.org)
  • These data suggest that activated myeloid cells and BAFF prime B cells for significant CpG-specific activation. (nih.gov)
  • B - Cell Activating Factor (BAFF) Inhibitors - Pipeline Insights, 2017" provides in depth insights on the pipeline drugs and their development activities around the B - Cell Activating Factor (BAFF) Inhibitors. (researchandmarkets.com)
  • This report also provides detailed information on the discontinued and dormant drugs that have gone inactive over the years for B - Cell Activating Factor (BAFF) Inhibitors. (researchandmarkets.com)
  • This report also assesses the B - Cell Activating Factor (BAFF) Inhibitors therapeutics by Monotherapy, Combination products, Molecule type and Route of Administration. (researchandmarkets.com)
  • We found that male progeny of i Myc Cα mice mated with mice transgenic (Tg) for CD257 (B-cell activating factor, BAFF) developed CD5 + B-cell leukemia resembling human chronic lymphocytic leukemia (CLL), which also displays a male gender bias. (pnas.org)
  • Surprisingly, leukemic cells of Myc/Baff Tg mice expressed higher levels of c-Myc than did B cells of i Myc Cα mice. (pnas.org)
  • We found that CLL cells of many patients with progressive disease also expressed high amounts of c-MYC, particularly CLL cells whose survival depends on nurse-like cells (NLC), which express high-levels of BAFF. (pnas.org)
  • We find that BAFF could enhance CLL-cell expression of c-MYC via activation the canonical IκB kinase (IKK)/NF-κB pathway. (pnas.org)
  • BAFF belongs to the tumor necrosis factor (TNF) ligand family and either is displayed on the cell surface or is released in a soluble form after cleavage from the plasma membrane by a furin-like protease ( 15 , 16 ). (aacrjournals.org)
  • BAFF is crucial for the survival, maturation, and differentiation of normal B cells ( 17 , 18 ). (aacrjournals.org)
  • Interestingly, neoplastic B-lineage lymphocytes express not only BAFF but also the receptors for BAFF, which, when ligated, can promote their cell survival in vitro ( 21 ). (aacrjournals.org)
  • BAFF-R expression was reported to be restricted to more mature B cells, starting at the T1 transitional B-cell stage ( 22 ). (aacrjournals.org)
  • Thus, BAFF-R is not present on murine pro-B or pre-B cells ( 20 ). (aacrjournals.org)
  • Because Ph-positive ALL cells typically represent transformed pre-B cells that do not produce surface IgM, the BAFF-R/BAFF pathway would not be anticipated to play a role in their survival or growth. (aacrjournals.org)
  • B-cell-activating factor (BAFF) plays a key role in promoting activation of autoimmune B cells. (semanticscholar.org)
  • Viral double-stranded RNA triggers Ig class switching by activating upper respiratory mucosa B cells through an innate TLR3 pathway involving BAFF. (semanticscholar.org)
  • Background: The B cell-activating factor of the TNF family (BAFF) is upregulated in autoimmune diseases, but a number of conflicting results have cast doubts on the reliability of the ELISA protocols currently used for its quantification. (aaccjnls.org)
  • The first of these is referred to as BAFF, for B cell- a ctivating f actor of the tumor-necrosis factor f amily ( 1 ), and the second as APRIL, for a pr oliferation- i nducing l igand ( 2 ). (aaccjnls.org)
  • Soluble variants of BAFF are the major contributors of its activity, through regulating the survival of B cells ( 3 ). (aaccjnls.org)
  • Additional evidence that BAFF is involved in autoantibody production includes its upregulation by B-cell depletion in patients with RA ( 8 ), and the inverse correlation between serum concentrations of BAFF before depletion of B cells and the length of time before their return in the blood of patients with SS ( 9 ). (aaccjnls.org)
  • Also intriguing is that increased serum concentrations of BAFF have been associated with the production of rheumatoid factor (RF) by some ( 10 ) but not other( 11 ) authors, or with that of anti-DNA antibody by some ( 12 ) but not other ( 13 ) authors. (aaccjnls.org)
  • Furthermore, no change in the activity associated with small latent TGF-β1 was noted in either mink lung epithelial cell or rat aortic smooth-muscle cell culture systems in the presence of TSP-1 (or TSP-1-derived peptides). (portlandpress.com)
  • Positive staining for cytokeratin 7 (a) and cytokeratin 19 (b) and the absence of staining with cytokeratin 20 (c) indicates the specificity of ductal epithelial cell origin. (biomedcentral.com)
  • PEF-1, an epithelial cell transcription factor which activates the long control region of human papillomavirus type 16, is glycosylated with N-acetylglucosamine. (microbiologyresearch.org)
  • Expression of LIS1 (platelet-activating factor acetylhydrolase isoform 1b) was assessed in CCA specimens and CCA cell lines by q-PCR and western blot. (biomedcentral.com)
  • These receptors are expressed mainly on mature B lymphocytes and their expression varies in dependence of B cell maturation (TACI is also found on a subset of T-cells and BCMA on plasma cells). (wikipedia.org)
  • 14,15 We and others have shown that stimulation of G-protein-coupled receptors effectively activates the Ca 2+ /calcineurin-dependent transcription factor NFAT in arterial smooth muscle. (ahajournals.org)
  • 16,17 More recently, we have shown that high glucose activates NFAT in intact arteries ex vivo by a mechanism involving the release of extracellular nucleotides (ie, UTP, UDP) acting on P2Y receptors, leading to increased intracellular Ca 2+ levels and subsequent activation of the calcineurin/NFAT signaling pathway. (ahajournals.org)
  • Besides their capacity to respond to cytokines, ILCs detect their targets through a series of cell surface-activating receptors recognizing microbial and nonmicrobial ligands. (sciencemag.org)
  • ET-3-induced metabolism of phosphoinositides was inhibited completely in Kupffer cells pretreated with ET-3, suggesting homologous ligand-induced desensitization of the ET-3 receptors. (biochemj.org)
  • It is commonly believed that these hypertrophy inducers activate phospholipase C (PLC) on binding to their G protein-coupled receptors, resulting in release of phosphoinositol from membrane phospholipids. (physiology.org)
  • Expression of functional Toll-like receptors by salivary gland epithelial cells: increased mRNA expression in cells derived from patients with primary Sjögren's syndrome. (semanticscholar.org)
  • Mesenchymal stem cells did not adhere to immobilized von Willebrand factor and did not express receptors for von Willebrand factor suggesting that the stimulation of the mesenchymal stem cell adhesion is a result of endothelial cell activation with von Willebrand factor. (biomedcentral.com)
  • We have previously shown that tryptase increases human bladder microvascular endothelial cell (HBMEC) calcium-independent phospholipase A 2 (iPLA 2 ) activity, resulting in the production of multiple biologically active phospholipid metabolites, including platelet-activating factor (PAF), that can mediate inflammation. (aspetjournals.org)
  • We hypothesized that von Willebrand factor is an auto/paracrine regulator of endothelial cell adhesiveness and studied the effect of von Willebrand factor on adhesion of mesenchymal stem cells to endothelial cells. (biomedcentral.com)
  • Cell adhesion assay and protein kinase inhibitors were used to evaluate the role of mitogen-activated protein kinases in the regulation of endothelial cell adhesiveness for mesenchymal stem cell. (biomedcentral.com)
  • Activation of p38 MAPK in endothelial cells by von Willebrand factor is responsible for the regulation of endothelial cell adhesiveness for mesenchymal stem cells. (biomedcentral.com)
  • Angiogenic growth factor-induced endothelial cell migration is a key step towards tumor angiogenesis. (cdc.gov)
  • The migration-stimulated caveolin rear translocation appears to play an important role in endothelial cell polarization and directional movement. (cdc.gov)
  • In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. (bloodjournal.org)
  • Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. (bloodjournal.org)
  • AND-34, a novel GDP exchange factor, is expressed constitutively at significant levels in murine splenic B cells, but not in murine splenic T cells or thymocytes. (jimmunol.org)
  • As previously reported for lymphoid cells transfected with constitutively active Cdc42, AND-34 overexpression inhibits SDF-1α-induced B cell polarization. (jimmunol.org)
  • We report here that ATF6 constitutively expressed as a 90-kDa protein (p90ATF6) is directly converted to a 50-kDa protein (p50ATF6) in ER-stressed cells. (psu.edu)
  • A signal transduction pathway activated by many cytokines has recently been elaborated. (bloodjournal.org)
  • These studies suggest that p130Cas and HEF1-associated AND-34 may regulate B cell adhesion and motility through a Cdc42-mediated signaling pathway. (jimmunol.org)
  • SMC phenotypic modulation is a critical event underlying atherosclerosis and in-stent restenosis that involves several signaling cascades, such as the calcineurin (Cn)/nuclear factor of activated T cells (NFAT) pathway. (ahajournals.org)
  • have found one such mechanism-cross-talk between the alternative complement pathway and natural killer (NK) cells and innate lymphoid cells (ILCs). (sciencemag.org)
  • They report that complement factor P (CFP), a positive regulator of the alternative complement pathway, binds NKp46, which is expressed on subsets of NK cells and ILC1 and ILC3. (sciencemag.org)
  • The calcineurin/NFAT3 pathway can be activated by classical hypertrophy inducers, including ANG II, endothelin-1 (ET-1), and catecholamines ( 27 , 49 ). (physiology.org)
  • It is suggested that this factor acts through an alternative pathway of CTL activation which is independent of specific stimulation by antigen. (ubc.ca)
  • therefore, we asked if 8-NH 2 -Ado could kill breast cancer cells without activating the p53-pathway. (aacrjournals.org)
  • Importantly 8-NH 2 -Ado was highly cytotoxic to triple-negative breast cancer cells and worked through a pathway that did not require wild-type p53 for cytoxicity. (aacrjournals.org)
  • Here, we studied the effects of MEF2A on the senescent phenotype of vascular endothelial cells (VEC) and downstream signaling pathway, and the association between plasma MEF2A levels and coronary artery disease (CAD). (aging-us.com)
  • These results suggested that MEF2A can directly up-regulate PI3K gene expression, and one of the molecular mechanisms of delaying effect of MEF2A on VEC cell senescence was SIRT1-expression activation through the PI3K/p-Akt pathway. (aging-us.com)
  • These studies identified a G protein-coupled pathway for PAF induction of gene expression and transcription factor activation, which differs from the mechanisms employed by other immediate-early gene inducers. (springer.com)
  • Investigation into the signaling pathway for IL-1α expression in response to IL-1 revealed a requirement for reactive oxygen species and activity of the transcription factor nuclear factor (NF)-κB. (arvojournals.org)
  • We found that ERBB4 activated the transcriptional coactivator YAP, which promotes organ and tissue growth and is inhibited by the Hippo tumor-suppressor pathway. (sciencemag.org)
  • This study identifies an ancillary, TNF-mediated pathway, whereby activated T cells can induce B cells to express enhanced levels of the important costimulatory molecules, CD80 and CD54. (docphin.com)
  • Importantly, we showed that cdk3 enhances epidermal growth factor-induced transformation of JB6 Cl41 cells and si-cdk3 suppresses Ras G12V /cdk3/ATF1-induced foci formation in NIH3T3 cells. (aacrjournals.org)
  • When cotransfected with activated H-Ras, cdk4 displayed oncogenic potential by provoking foci formation in primary rat embryo fibroblasts ( 7 ) and generating malignant human epidermal tumorigenesis ( 8 ). (aacrjournals.org)
  • Given the fact that epidermal growth factor (EGF) is an important mitogen for hepatocytes we searched for disease regulated proteins to improve an understanding of the molecular pathogenesis of EGF induced HCC. (biomedcentral.com)
  • Given that epidermal growth factor is an important mitogen for hepatocytes we were particularly interested in an understanding of the consequences of its targeted over-expression in liver. (biomedcentral.com)
  • NRG1 stimulated YAP activity to an extent comparable to that of EGF (epidermal growth factor) or LPA (lysophosphatidic acid), known activators of YAP. (sciencemag.org)
  • Donor-specific antibodies bind with high affinity to the vascular endothelium of graft and activate complement. (wikipedia.org)
  • Here, we sought to determine whether hyperglycemia activates NFAT in vivo and whether this leads to vascular complications. (ahajournals.org)
  • In the context of vascular remodeling, soluble factors, cytokines, hormones, and extracellular nucleotides have been shown to induce OPN expression. (ahajournals.org)
  • 18 Elevated extracellular glucose levels have also been shown to induce OPN expression in rat aortic vascular smooth muscle cells (VSMCs). (ahajournals.org)
  • Nuclear factor of activated T-cells (NFAT) is importantly implicated in pathological cardiac remodeling and vascular lesion formation. (ahajournals.org)
  • The phospholipid platelet-activating factor (PAF) is a pro-inflammatory lipid mediator which participates in vascular- and innate immunity-associated processes by increasing vascular permeability, by facilitating leukocyte adhesion to the endothelium, and by contributing to phagocyte activation. (frontiersin.org)
  • They include agents like vascular endothelial growth factor (VEGF) and blood vessel fibroblastic growth factor (bFGF). (thefreedictionary.com)
  • Increased vascular endothelial growth factor (VEGF) biosynthesis in vascular endothelial cells has been reported to play an obligatory role in promoting angiogenesis. (docphin.com)
  • Chlamydial and human HSP 60s therefore activate human vascular cell functions relevant to atherogenesis and lesional complications. (jci.org)
  • Although the current experiments do not pinpoint in vivo the precise cell lineage in the heart responsible for these effects, the authors find that knocking down Bcl10 in endothelial cells in vitro blunts Ang II-induced adhesion of monocytes to the endothelium. (ahajournals.org)
  • Recently, we reported that high glucose activates the Ca 2+ /calcineurin-dependent transcription factor nuclear factor of activated T cells (NFAT) in arteries ex vivo. (ahajournals.org)
  • The conversion of latent TGF-β1 into its biologically active 25kDa form is thought to be an important step in the regulation of TGF-β activity both in cell culture and in vivo . (portlandpress.com)
  • We conclude that TSP-1, either alone or in the presence of cultured smooth-muscle cells (a cell type known to activate latent TGF-β in vitro and in vivo ) is unable to activate latent TGF-β1. (portlandpress.com)
  • In vivo MCV1 abrogated NFAT-mediated T-cell activation in a model of PMA-elicited peritonitis, whereas topical application of MCV1 markedly reduced neointima formation in a mouse model of restenosis. (ahajournals.org)
  • We also found that TNF-α promoted the interaction between PIKE-A and AMP-activated protein kinase (AMPK) to suppress its kinase activity in vitro and in vivo. (diabetesjournals.org)
  • Whole blood from 11 RA patients and six healthy volunteers was incubated ex vivo with MTX, PT523, ZD1694 and, as a control, the DMARD sulphasalazine (SSZ) after T-cell stimulation with α-CD3/CD28. (biomedcentral.com)
  • In an ex vivo setting, two novel anti-folate drugs designed to circumvent MTX resistance proved to be very effective in inhibiting TNF-α production by activated T cells from RA patients and healthy volunteers. (biomedcentral.com)
  • Mast cell activation in vivo is often associated with areas of oedema and connective-tissue degradation. (wiley.com)
  • Since the mechanisms of MMP activation in vivo are poorly understood we have examined the potential of mast cell proteinases to activate the precursor forms of human collagenase (MMP-1), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9). (wiley.com)
  • LSCs are sufficient to perpetuate human leukemic cell growth in long-term culture assays and in the murine nonobese diabetic/severe combined immunodeficiency model system. (bloodjournal.org)
  • Overexpression of AND-34 in murine B cell lines activates the Rho family GTPase Cdc42, but not Rac, Rho, RalA, or Rap1. (jimmunol.org)
  • Paper II: Calcineurin-dependent NFAT isoforms are activated in the myocardium of aortic stenosis patients and their activation is reversed by relief of pressure overload in a murine model of reverse remodeling Ida G. Lunde, Biljana Skrbic, Theis Tønnessen, Heidi Kvaløy, Ulla H. Enger, Ivar Sjaastad, Geir Christensen, Cathrine R. Carlson. (uio.no)
  • B cell-activating factor (BCAF) has been characterized and partially purified from the supernatant of the murine tumor T cell line 373. (pasteur.fr)
  • Because matrilysin is produced in Paneth cells of the murine small intestine, where it participates in innate host defense by activation of prodefensins, we speculated that its expression would be influenced by bacterial exposure. (rupress.org)
  • Here we demonstrate that the transcription factor NFAT controls the program of T cell exhaustion. (nih.gov)
  • Our data show that NFAT promotes T cell anergy and exhaustion by binding at sites that do not require cooperation with AP-1. (nih.gov)
  • The NFAT family consists of four members (NFATc1-c4) originally described in T cells but later also demonstrated in cells outside the immune system. (ahajournals.org)
  • Here, we used a genomics approach to identify and validate NFAT gene targets activated during platelet-derived growth factor-BB (PDGF-BB)-induced SMC phenotypic modulation. (ahajournals.org)
  • Proteins involved in cell cycling have also been identified as NFAT dependent. (ahajournals.org)
  • In human aortic SMCs, platelet-derived growth factor BB (PDGF-BB)-mediated induction of cyclin D1 was attenuated by inhibitors of Cn/NFAT signaling. (ahajournals.org)
  • Paper I: Angiotensin II and norepinephrine activate specific calcineurin-dependent NFAT transcription factor isoforms in cardiomyocytes Ida G. Lunde, Heidi Kvaløy, Bjørg Austbø, Geir Christensen, Cathrine R. Carlson. (uio.no)
  • Their nuclear translocation and activity is controlled by the Ca 2+ -calmodulin-dependent phosphatase calcineurin that binds to and dephosphorylates the N-terminal portion of NFAT proteins upon T-cell activation ( 12 , 15 ). (asm.org)
  • In peripheral T lymphocytes, NFATc1 and NFATc2 are the most abundant NFAT factors. (asm.org)
  • Comparable to CsA, MCV1 prevents NFAT activation at nanomolar potency without impairing calcineurin phosphatase activity, nuclear factor-κB nuclear import, and general cell signaling. (ahajournals.org)
  • In contrast, CsA but not MCV1-activated basal level extracellular signal-regulated kinases activity and prevented nuclear import of calcineurin, independent of NFAT activation. (ahajournals.org)
  • We provide evidence that nuclear factor of activated T cells (NFAT), an essential transcription factor in T cell activation, is a target of barbiturate-mediated immunosuppression in human T lymphocytes. (aspetjournals.org)
  • In contrast, barbiturates suppressed the calcineurin-dependent dephosphorylation of NFAT in intact T cells and also inhibited the enzymatic activity of calcineurin in a cell-free system, excluding upstream regulation. (aspetjournals.org)
  • We therefore sought to determine whether CS stimulates pneumococcal adhesion to airway cells. (bmj.com)
  • Conclusion CSE stimulates PAFR-dependent pneumococcal adhesion to lower airway epithelial cells. (bmj.com)
  • A growth factor produced by the cell that stimulates the same cell to grow. (thefreedictionary.com)
  • Smith, TAD, Zanda, M & Fleming, IN 2013, ' Hypoxia stimulates 18F-Fluorodeoxyglucose uptake in breast cancer cells via hypoxia inducible factor-1 and AMP-activated protein kinase ', Nuclear Medicine and Biology , vol. 40, no. 6, pp. 858-864. (elsevier.com)
  • Bone marrow stromal cells support leukemic cell growth by the production of soluble factors such as CXCL12, interleukin-7, and Wnt proteins, as well as via cell-cell adhesion mediated by molecules such as VLA-4/VCAM1 ( 6 - 8 ). (aacrjournals.org)
  • We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. (bloodjournal.org)
  • STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. (bloodjournal.org)
  • The present results suggest that the stimulatory effects of ET-3 and PAF on the phosphodiesteric metabolism of phosphoinositides in Kupffer cells require different guanine-nucleotide-binding proteins. (biochemj.org)
  • Proteins synthesized in the endoplasmic reticulum (ER) of eukaryotic cells must be folded correctly before translocation out of the ER. (plantcell.org)
  • Secretory proteins are synthesized and folded in the endoplasmic reticulum (ER) of eukaryotic cells. (plantcell.org)
  • In addition, EGFR phosphorylation and shedding of the membrane-anchored heparin-binding EGF-like growth factor (pro-HB-EGF) ectodomain, as well as a rapid activation/phosphorylation of the classical survival proteins ERK, P70S6K and rS6 were induced upon sPLA2-IIA treatment. (csic.es)
  • Among cellular mechanisms that may underlie interstitial inflammation, it has been suggested that abnormally filtered proteins may have intrinsic renal toxicity and may serve as an early fosterer in tubular cells by activating the synthesis of vasoactive and proinflammatory substances ( 2 ). (asnjournals.org)
  • Evidence in chronic nephropathy induced by renal mass reduction and in passive Heymann nephritis in rats revealed that excess uptake of plasma proteins in proximal tubular cells precedes because the early stage is subsequently associated with an inflammatory reaction ( 12 ). (asnjournals.org)
  • In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. (mdpi.com)
  • In the present study, we generated a series of domain deletion mutants of caveolin-1 as GFP-fusion proteins and investigated domain or sequence that was required for caveolin-1 polarization in migrating cells. (cdc.gov)
  • The effect of hypoxia on FDG uptake, and key proteins involved in glucose transport and glycolysis, was studied in MCF7 and MDA231 breast cancer cell lines. (elsevier.com)
  • Molecular analysis indicated that hypoxia upregulated glut1 and 6-phosphofructo-2-kinase, key proteins involved in regulating glucose transport and glycolysis, and that these changes were induced by Hypoxia-Inducible factor 1 (HIF1) upregulation and/or AMP-activated protein kinase activation. (elsevier.com)
  • A better understanding of the underlying molecular mechanism is required to determine the value of FDG for studying tumour hypoxia.MethodsThe effect of hypoxia on FDG uptake, and key proteins involved in glucose transport and glycolysis, was studied in MCF7 and MDA231 breast cancer cell lines.ResultsHypoxia induced a dose- and time-dependent increase in FDG uptake. (elsevier.com)
  • Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. (semanticscholar.org)
  • Defective T cell differentiation in the absence of Jnk1. (semanticscholar.org)
  • Competence to synthesize collagenase in response to CB was acquired as a differentiation property by corneal stromal cells placed in culture, and did not require subculture. (arvojournals.org)
  • Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-κB-induced inflammatory mediators production in RAW 264.7 cells. (lenus.ie)
  • These gene activation events were independent of overt morphological differentiation of PC12 cells occurring both under conditions permissive and non-permissive for neurite outgrowth, and once established the new molecular phenotype was dependent upon the continued presence of NGF. (royalholloway.ac.uk)
  • These cells exhibit high microbicidal activity and induce inflammation. (hindawi.com)
  • Significantly, p130Cas promotes cell migration in a process dependent on Rac but not Ras, although the precise mechanism by which p130Cas complexes induce Rac activation remains unclear ( 16 ). (jimmunol.org)
  • However, in the absence of mitogen or antigen stimulation, IL-2 alone cannot induce CTL (except in the case of very high cell density). (ubc.ca)
  • Even then, corneal stasis may remain undisturbed, as corneal stromal cells are resistant to stimuli that would induce cells from other tissues to enter the cell cycle and initiate a fibrotic response. (arvojournals.org)
  • Bacteria did not induce matrilysin in other cell types, and expression of other metalloproteinases by epithelial cells was not affected by bacteria. (rupress.org)
  • We previously reported that anti-CD3-activated T cells (Ta) can induce expression of CD80 and CD54 (ICAM-1) on human B cells through a contact-dependent signal delivered to the CD40 molecule via the CD40 ligand. (docphin.com)
  • Moreover, soluble, recombinant TNF-alpha or TNF-beta can induce significant increases in B cell expression of CD80 and CD54. (docphin.com)
  • Using NSCLC cell lines, we evaluated how pStat3 expression relates to EGFR mutations and sensitivity of cells to gefitinib. (aacrjournals.org)
  • Cell lines with mutant EGFR have increased levels of pStat3 compared with cell lines without mutant EGFR and this correlates with their sensitivity to gefitinib. (aacrjournals.org)
  • We further demonstrated that the presence of an EGFR inhibitor (AG1478), a matrix metalloproteinase inhibitor (GM6001), an ADAM inhibitor (TAPI-1), and a HB-EGF neutralizing antibody abrogated the phenotype of activated microglia induced by the sPLA2-IIA. (csic.es)
  • Treatment of cells with EGFR inhibitor, AG1478, significantly blocked the PA-induced enhancement of NOX activity. (biomedcentral.com)
  • Here we show that VLDL (75 to 150 microg/mL) activates nuclear factor-kappaB (NF-kappaB), a transcription factor known to play a key role in regulation of inflammation. (nih.gov)
  • 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator of inflammation produced by inflammatory cells and also by renal glomerular mesangial cells. (aspetjournals.org)
  • Fractalkine might contribute to direct mononuclear cells into peritubular interstitium and enhance their adhesion property, which in turn would favor inflammation and disease progression. (asnjournals.org)
  • Inflammation is a complex and a tightly coordinated biological process driven by a wide array of cells and chemical mediators ( 1 ). (frontiersin.org)
  • This study confirmed that dapsone has anti-inflammatory effects on LPS-mediated inflammation via modulation of the number and function of inflammatory cells, providing new and useful information for clinicians and researchers. (vetsci.org)
  • Zimmerman, G. A., Prescott, S. M., and McIntyre, T. M. (1992) Platelet-activating factor: a fluid-phase and cell-associated mediator of inflammation. (springer.com)
  • Nuclear factor of activated T cells 2 interacting protein is a protein that in humans is encoded by the NFATC2IP gene. (wikipedia.org)
  • Expression of calcineurin and nuclear factor of activated T cells 1 in testis of rats with chronic fluorosis]. (fluoridealert.org)
  • Activation of the nuclear factor of activated T cells-3 (NFAT3) transcription factor has been shown to result from endocrine inducers of cardiomyocyte hypertrophy such as angiotensin II (ANG II) and serves as an important molecular regulator of cardiomyocyte hypertrophy. (physiology.org)
  • Cells respond to high osmolarity via the transcription factor nuclear factor of activated T cells (NFAT5). (uzh.ch)
  • Nuclear factor of activated T-cells, cytoplasmic 1 (943 aa, ~101 kDa) is encoded by the human NFATC1 gene. (semanticscholar.org)
  • NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus. (semanticscholar.org)
  • Our results suggest that VLDL may promote the development of atherosclerotic lesions by activation of the proinflammatory transcription factor NF-kappaB. (nih.gov)
  • Understanding the signals required to mediate efficient CpG-induced, antigen-independent and T-cell independent activation of B cells has implications for polyclonal B cell activation and the development of autoimmune diseases. (nih.gov)
  • These results indicate that Src kinase activation enhances the response of epithelial cells to TNF-alpha leading to increased invasion through mechanisms that involve production of reactive oxygen intermediates. (nih.gov)
  • In eukaryotic cells, cell cycle progression is driven by the sequential and periodic activation of cyclin/cdks, and dysregulation of the cell cycle is associated with cancer development ( 2 ). (aacrjournals.org)
  • Results showed the redox activation of MAP kinases down regulated the mRNA levels of AP-1 subunits in aqueous areca nut extract treated cells. (springer.com)
  • Chang MC et al (2004) The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation. (springer.com)
  • 7 Thus, NF-κB activation by the CARMA3 CBM signalosome in endothelial cells may facilitate recruitment of profibrotic inflammatory cells into the heart during hypertension. (ahajournals.org)
  • Unlike heat shock, activation of HSF by either hypo- or hyper-osmotic stress did not lead to an accumulation of heat-shock protein 70 (HSP70) mRNA in HeLa cells. (portlandpress.com)
  • Any TSP-mediated activation of TGF-β1 must depend on additional factor(s) not present in our systems. (portlandpress.com)
  • These acetylenic compounds were found to cause a time-dependent increase in activation of apoptotic signaling involving cleavage of caspase-9, caspase-3, and PARP, as well as apoptotic cell morphology in NSCLC cells, but not in normal fibroblasts. (aacrjournals.org)
  • They are involved in the activation of T cells by controlling the transcription of interleukin-2 (IL-2) and further lymphokine promoters. (asm.org)
  • Protein overload is a promoter of fractalkine gene induction mediated by NF-κB and p38 activation in proximal tubular cells. (asnjournals.org)
  • We have previously reported that activation of nuclear factor-κB (NF-κB) is causally associated with the enhanced cell survival of MCF+FIR cells derived from breast cancer MCF-7 cells after chronic exposure to fractionated ionizing radiation. (aacrjournals.org)
  • Taken together, these results suggest that NF-κB inhibits ERK activation to enhance cell survival during the development of tumor adaptive radioresistance. (aacrjournals.org)
  • Mitogen-activated protein kinases [i.e., extracellular signal-regulated kinase (ERK), c-jun NH 2 -terminal kinase (JNK), and p38], which all are closely related with NF-κB activation, are also involved in the radiation response ( 26 - 28 ). (aacrjournals.org)
  • B-cell-activating factor expressions in salivary epithelial cells after dsRNA virus infection depends on RNA-activated protein kinase activation. (semanticscholar.org)
  • The role of viruses in autoreactive B cell activation within tertiary lymphoid structures in autoimmune diseases. (semanticscholar.org)
  • In mammalian cells, inactivation of MAPK is achieved by a family of dual‐specificity MAPK phosphatases which target the two critical phosphorylation sites in the activation loop of MAPK ( Keyse, 1998 ). (embopress.org)
  • Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. (semanticscholar.org)
  • We used Affymetrix DNA microarrays, human protein phospho-MAPK array, Western blot, cell-based ELISA and flow cytometry analysis to study the activation of endothelial cells by von Willebrand factor. (biomedcentral.com)
  • Activation of ECs under stress conditions occurs rapidly and results in massive release of von Willebrand factor (vWF) from intracellular storage. (biomedcentral.com)
  • Deletion of the C-terminal cysteine cluster or mutation of the cysteine residues abolishes or markedly reduces the transcription activation activity of MTF1 and the ability of MTF1 to restore Mt1 induction in Mtf1 knockout cells. (cdc.gov)
  • Dröge, W. and Baeuerle, R A. (1992) Dithiocarbamates as potent inhibitors of nuclear factor KB activation in intact cells. (springer.com)
  • Since we have no evidence that mast cells express these four metalloenzymes, the release of mast cell serine proteinases following activation/degranulation could contribute to local metalloproteinase activation and subsequent matrix degradation. (wiley.com)
  • and high-molecular-weight kininogen, also called Fitzgerald , Flaujeac , or Williams factor , or contact activation cofactor . (thefreedictionary.com)
  • Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. (lenus.ie)
  • As such, the factors that regulate the expression of these accessory molecules may determine whether presentation of antigen leads to immune activation or anergy. (docphin.com)
  • Mice bearing a v-Myc myelocytomatosis viral oncogene homolog ( c-Myc ) transgene controlled by an Ig-alpha heavy-chain enhancer (i Myc Cα mice) rarely develop lymphomas but instead have increased rates of memory B-cell turnover and impaired antibody responses to antigen. (pnas.org)
  • During persistent antigen stimulation, CD8(+) T cells show a gradual decrease in effector function, referred to as exhaustion, which impairs responses in the setting of tumors and infections. (nih.gov)
  • Expression of immune accessory molecules, such as CD80 (B7-1), on antigen-presenting cells governs whether such cells can activate antigen-specific T cells. (docphin.com)
  • In B cell lines, anti-IgM treatment up-regulates AND-34 transcript levels. (jimmunol.org)
  • These observations prompted us to study if the interaction of bacteria with host cells regulates the expression of matrilysin. (rupress.org)
  • These dada provide the first direct evidence for a role of p38 MAPK in mediating hypoxia-induced increase in VEGF biosynthesis in human endothelial cells. (docphin.com)
  • In contrast, mutant ATF6 representing the cytoplasmic region translocates into the nucleus and activates transcription of the endogenous GRP78/BiP gene. (psu.edu)
  • In nonimmune cells, CARMA3 substitutes for CARMA1 in the CBM signalosome, but either of these CARMAs must complex with Bcl10 to trigger the NF-κB inflammatory signaling cascade. (ahajournals.org)
  • Tryptase released from elevated numbers of activated mast cells is a proposed mediator of the inflammatory process in IC. (aspetjournals.org)
  • In response to a variety of insults, microglial cells produce high levels of inflammatory cytokines that are often involved in neuronal injury, and play an important role in the recognition, engulfment, and clearance of apoptotic cells and/or invading microbes. (csic.es)
  • Secreted phospholipase A2-IIA (sPLA2-IIA), an enzyme that interacts with cells involved in the systemic immune/inflammatory response, has been found up-regulated in the cerebrospinal fluid and brain of AD patients. (csic.es)
  • The hallmarks of activated microglia analyzed include: mitogenic response, phagocytic capabilities and induction of inflammatory mediators. (csic.es)
  • Among these molecules, the phospholipid platelet-activating factor (PAF) potent pro-inflammatory lipid mediator. (frontiersin.org)
  • The present study investigated the anti-inflammatory effects of dapsone on bone marrow cells (BMs), especially upon exposure to lipopolysaccharide (LPS). (vetsci.org)
  • Interestingly, dapsone modulated the inflammatory cells, including granulocytes in LPS-treated BMs, by inducing cell death. (vetsci.org)
  • ECs show limited adhesiveness for cells circulating in the bloodstream, however, they became activated after exposure to inflammatory or stress factors. (biomedcentral.com)
  • To investigate whether two new-generation anti-folate drugs, PT523 (DHFR-inhibitor) and ZD1694 (TS-inhibitor), have equal or better anti-inflammatory capacity compared with MTX based on their capacity to inhibit tumour necrosis factor alpha (TNF-α) production by activated T cells. (biomedcentral.com)
  • These factors are active in healing wounds, chronic inflammatory conditions, retrolental fibroplasia, and malignant tumors, which require new blood vessels for continued growth. (thefreedictionary.com)
  • B cell AND-34 associates with both the docking molecules p130Cas and HEF1. (jimmunol.org)
  • p130Cas and HEF1 are a structurally related pair of such docking molecules that localize to the focal adhesion complex, assembling members of adhesion and growth factor-related signaling cascades ( 10 , 11 ). (jimmunol.org)
  • In particular, growth factors and bioactive molecules derived from activated platelets emerged as promising therapeutic agents acting as trigger for repair of tissue lesions and restoration of tissue functions. (deepdyve.com)
  • These molecules are rapidly biosynthesized by myeloid and epithelial cells within seconds to minutes of acute stimulation of different origins ( 1 , 4 ). (frontiersin.org)
  • which are specialized defense cells that secrete defensins, lysozyme, phospholipase A2, and other antimicrobial molecules ( Ouellette 1997 ). (rupress.org)
  • Moreover, a decreased phosphorylation of the growth factor signaling kinases Akt, mTOR, and ERK was evident and an increased phosphorylation of JNK was observed. (aacrjournals.org)
  • Further irradiation with 30 fractions of radiation also inhibited MEK/ERK phosphorylation in paired cell lines of MCF+FIR and parental MCF-7 cells. (aacrjournals.org)
  • However, major heterodimers of NF-κB p65 and p50, which are activated quickly following the phosphorylation and proteolysis of IκB ( 21 , 22 ), can function as pleiotropic gene regulators ( 23 ). (aacrjournals.org)
  • AMPK can be activated by AMP binding or phosphorylation by other kinases like liver kinase B1 or Ca 2+ /calmodulin-dependent protein kinase kinase β ( 13 , 14 ). (diabetesjournals.org)
  • Both p42 and p44MAPK are activated by dual phosphorylation on a threonine and a tyrosine residue, achieved by the dual‐specificity kinase MKK1/2. (embopress.org)
  • In accordance with this report, an increase in ERK1/2 phosphorylation and VEGF biosynthesis was observed in ECV304 cells cultured in hypoxia, and this increase was blocked by PD98059. (docphin.com)
  • It can be concluded that phagocytosis of apoptotic cells engages CD36 and PAFR, possibly in lipid rafts, and this is required for optimal efferocytosis and the establishment of the macrophage regulatory phenotype. (hindawi.com)
  • AND-34 binds by its GDP exchange factor domain to the C terminus of HEF1, a region of HEF1 previously implicated in apoptotic, adhesion, and cell cycle-regulated signaling. (jimmunol.org)
  • Interestingly, 8-NH 2 -Ado caused the MDA-MB-231 cells to detach from the plate with only limited evidence of apoptotic cell death markers and the cell death was not inhibited by Z-VAD. (aacrjournals.org)
  • One such mechanism may include adhesion of MSCs to distressed/apoptotic endothelial cells (ECs). (biomedcentral.com)
  • It is expressed as a membrane-bound type II transmembrane protein on various cell types including monocytes, dendritic cells and bone marrow stromal cells. (wikipedia.org)
  • It is controversial whether naïve B cells are directly activated in response to TLR9 ligand, CpG ODN. (nih.gov)
  • Here, we demonstrate that another molecule in the CD40-ligand family, namely tumor necrosis factor-alpha (TNF-alpha), also plays a role in the Ta-mediated induction of CD80 or CD54 on human B cells. (docphin.com)
  • Both the frequency of CSF-producing cells and the average production per positive cell depended on the density of the immobilized stimulating ligand, indicating that the response of each cell is not an all-or-none phenomenon but varies with the strength of stimulation. (sdu.dk)
  • While IL-4, IL-5, and IL-13 mRNA expression was also enhanced in lymph node cells from the lungs of infected NFATc2 −/− mice, the number of T cells secreting Th2-type lymphokines remained the same in mice infected with N. brasiliensis . (asm.org)
  • The mRNA expression of VEGF in THP-1 cells and HCAECs was also augmented by PPARγ activators, troglitazone (TRO), and 15-deoxy-Δ 12,14 -prostaglandin J 2 (PGJ2). (elsevier.com)
  • Numerous studies have appeared describing the biologic relevance of stem cells, as well as their specific cellular and molecular properties. (bloodjournal.org)
  • Consistent with this, a subpopulation of AND-34 overexpressing B cells have long filamentous actin-containing cellular extensions. (jimmunol.org)
  • When energy supply is insufficient (e.g., fasting and exercise), cellular AMPK is activated and phosphorylates the downstream acetyl-CoA carboxylase (ACC), which promotes the mitochondrial transportation of FA for β-oxidation and hence elevated ATP production ( 15 ). (diabetesjournals.org)
  • The maturation of cytotoxic T lymphocyte (CTL) effectors from CTL precursors (CTLp) requires specific signals mediated through cellular interactions and soluble factors. (ubc.ca)
  • LPS distinctly activated BMs with several characteristics including high cellular activity, granulocyte changes, and tumor necrosis factor alpha (TNF-α) production increases. (vetsci.org)
  • Snyder, F. (1990) Platelet-activating factor and related acetylated lipids as potent biologically active cellular mediators. (springer.com)
  • To investigate the role of miR-144 in cancer cells, we examined the cellular effects of miR-144 overexpression. (biomedcentral.com)
  • Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. (bloodjournal.org)
  • The absence of staining for myeloperoxidase (MPO) (d), CD45 (e), CD20 (f), CD3 (g) and smooth muscle actin (h) before (subpanels 1 in (d-h)) and after (subpanels 2 in (d-h)) stimulation with IFN-α excludes the possibility of contamination with myeloid cell. (biomedcentral.com)
  • Negative staining with myeloperoxydase (MPO) (k) and CD45 (l) excludes the possibility of contamination with myeloid cells. (biomedcentral.com)
  • This interaction triggers signals essential for the formation and maintenance of B cell, thus it is important for a B-cell survival. (wikipedia.org)
  • In particular, it is critical to understand how malignant stem cells regulate growth and survival. (bloodjournal.org)
  • 20 Importantly, the active form of NF-κB is known to have antiapoptotic activity and is thereby considered to be a key survival factor for several types of cancer. (bloodjournal.org)
  • Subset-specific transplanted cells were correlated with acute graft-versus-host disease (aGVHD), chronic GVHD (cGVHD), malignant disease relapse, nonrelapse mortality, and overall survival. (osu.edu)
  • Granulocyte Colony-Stimulating Factor-Mobilized Allografts Contain Activated Immune Cell Subsets Associated with Risk of Acute and Chronic Graft-versus-Host Disease. (osu.edu)
  • We defined associations among immune cell subsets in granulocyte colony-stimulating factor (G-CSF)-mobilized allografts and clinical outcomes after allogeneic hematopoietic cell transplantation (alloHCT). (osu.edu)
  • First, ATF3 is induced in beta cells by signals relevant to beta-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate. (garvan.org.au)
  • Upon challenging Kupffer cells with both ET-3 and PAF, an additive stimulation of phosphoinositide metabolism was observed, suggesting that the actions of these factors may be exerted on separate phosphoinositide pools. (biochemj.org)
  • In contrast to the increased production of prostaglandins E2 and D2 observed upon stimulation of Kupffer cells with PAF, ET-3 stimulated the biosynthesis of prostaglandin E2 only. (biochemj.org)
  • Figure 1 shows that prior to infection, T cells from the mediastinal lymph nodes (MLN), mesenteric lymph nodes (MESLN), and spleens of both types of mice secreted no or only very low amounts of IL-4 and IL-5 after in vitro stimulation with anti-CD3 (α-CD3) antibodies (Abs) and IL-2 (for descriptions of cell preparations and enzyme-linked immunosorbent assays [ELISAs], see reference 2 ). (asm.org)
  • In mammalian cells, mitogenic stimulation triggers the translocation of p42/p44MAPK from the cytoplasm to the nucleus, whereas the other protein kinases of the module remain cytosolic. (embopress.org)
  • Addition of NGF to cultured PC12 cells produced increases in mRNAs corresponding to the 68 kd neurofilament protein (NF68) and the Thy-1 glycoprotein within 24 h, with maximal effects of some 90- and 45-fold stimulation (relative to beta-actin mRNA) being observed after 12 and 4 days of treatment, respectively. (royalholloway.ac.uk)
  • The extracellular matrix (ECM) 1 of the corneal stroma undergoes an unusually slow rate of turnover and remodeling, and the stromal cells, or" keratocytes" replicate at a very slow rate. (arvojournals.org)
  • Tryptase and chymase are the major serine proteinases released by mast cells, but they appear to have little activity on most components of the extracellular matrix. (wiley.com)
  • We have demonstrated previously that an exposure of mammalian cells to hypo-osmotic stress, either in growth medium (30% growth medium and 70% water) or in binary solution containing sorbitol and water, prominently induced the DNA-binding activity of the heat-shock transcription factor (HSF1) [Huang, Caruccio, Liu and Chen (1995) Biochem. (portlandpress.com)
  • The signal transduction mechanism that triggers the ER stress response has been characterized extensively in yeast and mammalian cells. (plantcell.org)
  • In mammalian cells, three well‐characterized modules co‐exist: p42/p44MAPK, p38MAPK and JNK cascades (for a review see Cano and Mahadevan, 1995 ). (embopress.org)
  • Substantial progress in the understanding of systemic lupus erythematosus (SLE), 1 rheumatoid arthritis (RA), and primary Sjögren syndrome (SS) occurred with the discovery of 2 new tumor necrosis factor family members. (aaccjnls.org)
  • Also controls gene expression in embryonic cardiac cells. (rcsb.org)
  • The genetic locus of cdk3 was mapped to the chromosome 17q22-qter region, where cdk3 was involved in a chromosome rearrangement in a breast cancer cell line possibly resulting in an alteration of cdk3 gene expression or an abnormal transcript ( 23 ). (aacrjournals.org)
  • In contrast, primary AML CD34 + cells display readily detectable NF-κB activity as assessed by electrophoretic mobility shift assay and gene expression studies. (bloodjournal.org)
  • Gene expression profiling has revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two distinct diseases. (rupress.org)
  • Thus the relocalization of MAPK to the nucleus appears to be an important regulatory step for mitogen‐induced gene expression and cell cycle re‐entry. (embopress.org)
  • Rosen, C. A. and Mackman, N. (1994) Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site. (springer.com)
  • We found that activated B-cell factor-1 (ABF-1) binds to this site in vitro and suppresses reporter gene expression, but only in the presence of the LTA+80A allele. (ox.ac.uk)
  • Our results relate the progression of infection to cell cycle phases, and define a precise temporal order of viral gene expression. (nature.com)
  • 4 In lymphocytes, the CBM signalosome includes caspase recruitment domain 11 (CARMA1), B cell lymphoma/leukemia 10 (Bcl10), and mucosa-associated lymphoid tissue lymphoma translocation protein 1. (ahajournals.org)
  • Indeed, NFATc1-deficient (−/−) lymphocytes showed a significant decrease in Th2 responses ( 11 , 18 ), and T cells doubly deficient for NFATc1 and NFATc2 were additionally defective in the synthesis of the Th1-type lymphokines IFN-γ and IL-2 ( 9 ). (asm.org)
  • We fused concanavalin A-stimulated spleen lymphocytes of C57BL/6N mice with the AKR T-cell lymphoma BW-5147 G1.4. (elsevier.com)
  • In cultured myotubes, TNF-α suppresses the activities of AMP-activated protein kinase (AMPK), reduces fatty acid (FA) oxidation, and enhances lipid accumulation ( 12 ). (diabetesjournals.org)
  • Since MAPK has been shown to phosphorylate and activate nuclear targets, such as the transcription factor Elk1, it has been proposed, but not yet demonstrated, that MAPK nuclear translocation could represent a critical step in signal transduction. (embopress.org)
  • In contrast, prevention of MAPK nuclear translocation strongly inhibited Elk1‐dependent gene transcription and the ability of cells to reinitiate DNA replication in response to growth factors. (embopress.org)
  • Treatment of endothelial cells with von Willebrand factor activated ERK-1,2 and p38 MAPK without an effect on gene or cell surface expression of E-selectin, P-selectin, VCAM1 and ICAM1. (biomedcentral.com)
  • Cyclin-dependent kinases (cdk) are serine/threonine protein kinases that play essential roles in the control of cell cycle progression by interacting with a variety of regulators and substrates ( 1 ). (aacrjournals.org)
  • Hemizygous disruption of cdc25 was shown to inhibit cell transformation and mammary tumorigenesis in mice ( 12 ). (aacrjournals.org)
  • Both PT523 and D1694 turned out to inhibit TNF-α production by activated T cells much more efficiently than MTX (5-15 times). (biomedcentral.com)
  • Neutralizing mAbs specific for TNF-alpha can inhibit B cell expression of CD80 or CD54 that is induced when B cells are cultured with Ta cells or in Ta-cell conditioned media. (docphin.com)

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