Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Transcription Factor RelA: A subunit of NF-kappa B that is primarily responsible for its transactivation function. It contains a C-terminal transactivation domain and an N-terminal domain with homology to PROTO-ONCOGENE PROTEINS C-REL.NADPH Oxidase: A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.Class Ia Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the heterodimerization of a p110 catalytic and a p85, p55, or p50 regulatory subunit. This subclass of enzymes is a downstream target of TYROSINE KINASE RECEPTORS and G PROTEIN-COUPLED RECEPTORS.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Receptors, Interleukin: Cell surface proteins that bind interleukins and trigger intracellular changes influencing the behavior of cells.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Interleukin-6: A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.Interleukin-2: A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.Santonin: Anthelmintic isolated from the dried unexpanded flower heads of Artemisia maritima and other species of Artemisia found principally in Russian and Chinese Turkestan and the Southern Ural region. (From Merck, 11th ed.)Cell Line: Established cell cultures that have the potential to propagate indefinitely.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.NF-kappa B p50 Subunit: A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p105 precursor protein and is capable of forming dimeric complexes with itself or with TRANSCRIPTION FACTOR RELA. It regulates expression of GENES involved in immune and inflammatory responses.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Mice, Inbred C57BLInterleukin-12 Subunit p35: A subunit of interleukin-12. It binds to the INTERLEUKIN-12 SUBUNIT P40 via a disulfide bond that results in the active cytokine.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Interleukin-4: 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.Interleukins: 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.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Interleukin-10: 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.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.Lipopolysaccharides: 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)Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Superoxides: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.PhosphoproteinsRibonucleotide ReductasesInterferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Receptors, Interleukin-2: Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.Kinetics: The rate dynamics in chemical or physical systems.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Interleukin-23 Subunit p19: A subunit of interleukin-23. It combines with INTERLEUKIN-12 SUBUNIT P40, which is shared between the two cytokines, to form in the active interleukin-23 cytokine.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Interleukin-12: A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.Interleukin-12 Subunit p40: A cytokine subunit that is a component of both interleukin-12 and interleukin-23. It binds to the INTERLEUKIN-12 SUBUNIT P35 via a disulfide bond to form interleukin-12 and to INTERLEUKIN-23 SUBUNIT P19 to form interleukin-23.Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.AcetophenonesCloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cell Line, Tumor: A cell line derived from cultured tumor cells.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Mice, Inbred BALB CEscherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.NADH, NADPH Oxidoreductases: A group of oxidoreductases that act on NADH or NADPH. In general, enzymes using NADH or NADPH to reduce a substrate are classified according to the reverse reaction, in which NAD+ or NADP+ is formally regarded as an acceptor. This subclass includes only those enzymes in which some other redox carrier is the acceptor. (Enzyme Nomenclature, 1992, p100) EC 1.6.Interleukin-3: A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Interleukin-5: A cytokine that promotes differentiation and activation of EOSINOPHILS. It also triggers activated B-LYMPHOCYTES to differentiate into IMMUNOGLOBULIN-secreting cells.Molecular Weight: The sum of the weight of all the atoms in a molecule.Interleukin-18: A cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK CELLS and CYTOTOXIC T-LYMPHOCYTES, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Interleukin-13: A cytokine synthesized by T-LYMPHOCYTES that produces proliferation, immunoglobulin isotype switching, and immunoglobulin production by immature B-LYMPHOCYTES. It appears to play a role in regulating inflammatory and immune responses.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Receptors, Interleukin-4: Receptors present on a wide variety of hematopoietic and non-hematopoietic cell types that are specific for INTERLEUKIN-4. They are involved in signaling a variety of immunological responses related to allergic INFLAMMATION including the differentiation of TH2 CELLS and the regulation of IMMUNOGLOBULIN E production. Two subtypes of receptors exist and are referred to as the TYPE I INTERLEUKIN-4 RECEPTOR and the TYPE II INTERLEUKIN-4 RECEPTOR. Each receptor subtype is defined by its unique subunit composition.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Proton-Translocating ATPases: Multisubunit enzymes that reversibly synthesize ADENOSINE TRIPHOSPHATE. They are coupled to the transport of protons across a membrane.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Receptors, Interleukin-6: Cell surface receptors that are specific for INTERLEUKIN-6. They are present on T-LYMPHOCYTES, mitogen-activated B-LYMPHOCYTES, and peripheral MONOCYTES. The receptors are heterodimers of the INTERLEUKIN-6 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR GP130.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Interleukin-13 Receptor alpha1 Subunit: An interleukin receptor subunit with specificity for INTERLEUKIN-13. It dimerizes with the INTERLEUKIN-4 RECEPTOR ALPHA SUBUNIT to form the TYPE II INTERLEUKIN-4 RECEPTOR which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13. Signaling of this receptor subunit occurs through the interaction of its cytoplasmic domain with JANUS KINASES such as the TYK2 KINASE.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Interleukin-11: A lymphohematopoietic cytokine that plays a role in regulating the proliferation of ERYTHROID PRECURSOR CELLS. It induces maturation of MEGAKARYOCYTES which results in increased production of BLOOD PLATELETS. Interleukin-11 was also initially described as an inhibitor of ADIPOGENESIS of cultured preadipocytes.Interleukin-17: A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.Th2 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Vaccines, Subunit: Vaccines consisting of one or more antigens that stimulate a strong immune response. They are purified from microorganisms or produced by recombinant DNA techniques, or they can be chemically synthesized peptides.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Polymerase Chain Reaction: 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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Interleukin-15: Cytokine that stimulates the proliferation of T-LYMPHOCYTES and shares biological activities with IL-2. IL-15 also can induce proliferation and differentiation of B-LYMPHOCYTES.Receptors, Interleukin-13: Cell surface receptors for INTERLEUKIN-13. Included under this heading are the INTERLEUKIN-13 RECEPTOR ALPHA2 which is a monomeric receptor and the INTERLEUKIN-4 RECEPTOR TYPE II which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13.Th1 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Vacuolar Proton-Translocating ATPases: Proton-translocating ATPases that are involved in acidification of a variety of intracellular compartments.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Interleukin-7: 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.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Glycoprotein Hormones, alpha Subunit: The alpha chain of pituitary glycoprotein hormones (THYROTROPIN; FOLLICLE STIMULATING HORMONE; LUTEINIZING HORMONE) and the placental CHORIONIC GONADOTROPIN. Within a species, the alpha subunits of these four hormones are identical; the distinct functional characteristics of these glycoprotein hormones are determined by the unique beta subunits. Both subunits, the non-covalently bound heterodimers, are required for full biologic activity.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.STAT3 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Electron Transport Complex IV: A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane.Protein Phosphatase 2: A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.T-Lymphocytes, Helper-Inducer: Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.Interleukin-23: A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-23 is comprised of a unique 19 kDa subunit and 40 kDa subunit that is shared with INTERLEUKIN-12. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cellsProtein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Interleukin-1alpha: An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity.Dendritic 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).Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Bacterial Proteins: Proteins found in any species of bacterium.Cytotoxicity, Immunologic: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Receptors, Interleukin-5: Cell surface receptors that are specific for INTERLEUKIN-5. They are heterodimeric proteins consisting of the INTERLEUKIN-5 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT. Signaling from interleukin-5 receptors can occur through interaction of their cytoplasmic domains with SYNTENINS.Receptors, Interleukin-1 Type I: An interleukin-1 receptor subtype that is involved in signaling cellular responses to INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The binding of this receptor to its ligand causes its favorable interaction with INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN and the formation of an activated receptor complex.Cytokine Receptor gp130: A cytokine receptor that acts through the formation of oligomeric complexes of itself with a variety of CYTOKINE RECEPTORS.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Mice, Inbred C3HReceptors, Interleukin-3: High affinity receptors for INTERLEUKIN-3. They are found on early HEMATOPOIETIC PROGENITOR CELLS; progenitors of MYELOID CELLS; EOSINOPHILS; and BASOPHILS. Interleukin-3 receptors are formed by the dimerization of the INTERLEUKIN-3 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Receptors, Interleukin-12: Cell surface receptors for INTERLEUKIN-12. They exist as dimers of beta 1 and beta 2 subunits. Signaling from interleukin-12 receptors occurs through their interaction with JANUS KINASES.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Antigens, Differentiation, T-Lymphocyte: Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Mice, Inbred Strains: 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.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Ribosomes: Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.Cross-Linking Reagents: Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Sodium-Potassium-Exchanging ATPase: An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).STAT6 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-4. Stat6 has been shown to partner with NF-KAPPA B and CCAAT-ENHANCER-BINDING PROTEINS to regulate GENETIC TRANSCRIPTION of interleukin-4 responsive GENES.Killer Cells, Lymphokine-Activated: Cytolytic lymphocytes with the unique capacity of killing natural killer (NK)-resistant fresh tumor cells. They are INTERLEUKIN-2-activated NK cells that have no MAJOR HISTOCOMPATIBILITY COMPLEX restriction or need for antigen stimulation. LAK cells are used for ADOPTIVE IMMUNOTHERAPY in cancer patients.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Ribosomal Proteins: Proteins found in ribosomes. They are believed to have a catalytic function in reconstituting biologically active ribosomal subunits.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Multienzyme Complexes: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
... which work by targeting the p40 subunit. However, the p40 subunit is also present in Interleukin 12 (IL-12) and causes serious ... Alphabody CMPX-1023 has been successfully developed to target the p19 subunit of Interleukin 23 (IL-23) and has entered ... In brief, IL-23 is a pro-inflammatory cytokine that has been implicated in autoimmune inflammatory diseases like psoriasis, ... Mouse studies and X-ray crystallography studies on IL-23 in complex with the Alphabody confirmed specific binding to p19 only. ...
"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12 ... IL-12B is a common subunit of interleukin 12 and Interleukin 23. This gene encodes a subunit of interleukin 12, a cytokine that ... Subunit beta of interleukin 12 (also known as IL-12B, natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation ... Interleukin-12 p40 also serves as a subunit of Interleukin 23. GRCh38: Ensembl release 89: ENSG00000113302 - Ensembl, May 2017 ...
Knockout mice deficient in either p40 or p19, or in either subunit of the IL-23 receptor (IL-23R and IL12R-β1) develop less ... Experimental work revealed that p19 formed a heterodimer by binding to p40, a subunit of IL-12. This new heterodimer was named ... November 2000). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as ... has been identified and is composed of IL-12R β1 and IL-23R. IL-23 is an important part of the inflammatory response against ...
2003). "Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain". Nature. ... Lira's lab has also made important contributions to the study of IL-23, a cytokine that affects development of inflammatory and ... "CXCL13 expression in the gut promotes accumulation of IL-22-producing lymphoid tissue-inducer cells, and formation of isolated ... 2001). "Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and ...
IL-12p40) subunit (that is shared with IL12) and the IL23A (IL-23p19) subunit. A functional receptor for IL-23 (the IL-23 ... "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12 ... has been identified and is composed of IL-12R β1 and IL-23R. IL-23 was first described by Robert Kastelein and colleagues at ... did not produce the same results as those targeting IL-12p40 as would have been expected if both subunits formed part of IL-12 ...
"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12 ... p19 subunit) hence preventing it from binding cell receptors that would otherwise be activated by its presence. Cmax 8.09 µg/mL ... July 2017 Janssen Submits Application to EMA Seeking Approval of Anti-Interleukin-23 Monoclonal Antibody Guselkumab for the ... Ustekinumab, a monoclonal antibody targeting both IL-12 and IL-23 and used to treat plaque psoriasis, launched in the United ...
2001). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct ... Interleukin 12 receptor, beta 1 is a subunit of the interleukin 12 receptor. IL12RB1, is its human gene. IL12RB1 is also known ... 1995). "Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist". Eur. J. Immunol. 25 (1): 200-6. doi:10.1002/eji ... Igarashi O, Yamane H, Imajoh-Ohmi S, Nariuchi H (1998). "IL-12 receptor (IL-12R) expression and accumulation of IL-12R beta 1 ...
... binds to the p19 sub-unit of IL23, IL23A, preventing receptor activation and thereby disrupting the IL23/IL17 axis ... Risankizumab also known as BI-655066 is a humanized monoclonal antibody targeting interleukin 23A (IL-23A). Risankizumab is ... The IL23/IL17 axis plays an important role in the development of chronic inflammation, with potential genetic links between the ... September 2014). "The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing". Nat Rev Immonol. 9 (14): 585-600. doi: ...
... fibrillary acidic protein glycoprotein IB GSTA1 HAS2 gene expression Her5 hMYADM HSA hsp25 Id2 IL-3Ralpha Integrins interleukin ... Stahl J, Wobus AM, Ihrig S, Lutsch G, Bielka H (September 1992). "The small heat shock protein hsp25 is accumulated in P19 ... April 2005). "Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID". Genes & Development. 19 (7): ... Christensen JL, Weissman IL (December 2001). "Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to ...
26S proteasome non-ATPase regulatory subunit 14, also known as 26S proteasome non-ATPase subunit Rpn11, is an enzyme that in humans is encoded by the PSMD14 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex. Nine subunits Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, SEM1(Yeast analogue for human protein DSS1), and Rpn12 form the lid sub complex of 19S regulatory particle for proteasome complex. The gene PSMD14 encodes one of 26S proteasome non-ATPase ...
26S proteasome non-ATPase regulatory subunit 1, also as known as 26S Proteasome Regulatory Subunit Rpn2 (systematic nomenclature), is a protein that in humans is encoded by the PSMD1 gene. This protein is one of the 19 essential subunits that contributes to the complete assembly of 19S proteasome complex. The gene PSMD1 encodes the largest non-ATPase subunit of the 19S regulator base, which is responsible for substrate recognition and binding. The human PSMD1 gene has 25 exons and locates at chromosome band 2q37.1. The human protein 26S proteasome non-ATPase regulatory subunit 1 is 106 kDa in size and composed of 953 amino ...
Proteasome subunit alpha type-3 also known as macropain subunit C8 and proteasome component C8 is a protein that in humans is encoded by the PSMA3 gene. This protein is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological ...
Proteasome subunit beta type-10 as known as 20S proteasome subunit beta-2i is a protein that in humans is encoded by the PSMB10 gene. This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation. The immunoproteasome appears to have a pivotal role in modulating NFκB signaling. This gene ...
ATP-binding cassette transporters (ABC transporters) are members of a transport system superfamily that is one of the largest and is possibly one of the oldest families with representatives in all extant phyla from prokaryotes to humans. ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated ATPases. The ATPase subunits utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to energize the translocation of various substrates across membranes, either for uptake or for export of the substrate. Most ...
Proteasome activator complex subunit 3 is a protein that in humans is encoded by the PSME3 gene. The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed ...
26S proteasome non-ATPase regulatory subunit 13 is an enzyme that in humans is encoded by the PSMD13 gene. The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed ...
Voltage-dependent calcium channel subunit alpha2delta-2 is a protein that in humans is encoded by the CACNA2D2 gene.[5] This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein ...
cite journal ,last=Viollet ,first=Benoît ,last2=Andreelli ,first2=Fabrizio ,last3=Jørgensen ,first3=Sebastian B. ,last4=Perrin ,first4=Christophe ,last5=Geloen ,first5=Alain ,last6=Flamez ,first6=Daisy ,last7=Mu ,first7=James ,last8=Lenzner ,first8=Claudia ,last9=Baud ,first9=Olivier ,last10=Bennoun ,first10=Myriam ,last11=Gomas ,first11=Emmanuel ,last12=Nicolas ,first12=Gaël ,last13=Wojtaszewski ,first13=Jørgen F.P. ,last14=Kahn1 ,first14=Axel ,last15=Carling ,first15=David ,last16=Schuit ,first16=Frans C. ,last17=Birnbaum ,first17=Morris J. ,last18=Richter ,first18=Erik A. ,last19=Burcelin ,first19=Rémy ,last20=Vaulont ,first20=Sophie ,display-authors=5 ,date=January 2003 ,title=The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity ,url=http://www.jci.org/articles/view/16567 ,journal=The Journal of Clinical ...
cite journal ,last=Viollet ,first=Benoît ,last2=Andreelli ,first2=Fabrizio ,last3=Jørgensen ,first3=Sebastian B. ,last4=Perrin ,first4=Christophe ,last5=Geloen ,first5=Alain ,last6=Flamez ,first6=Daisy ,last7=Mu ,first7=James ,last8=Lenzner ,first8=Claudia ,last9=Baud ,first9=Olivier ,last10=Bennoun ,first10=Myriam ,last11=Gomas ,first11=Emmanuel ,last12=Nicolas ,first12=Gaël ,last13=Wojtaszewski ,first13=Jørgen F.P. ,last14=Kahn1 ,first14=Axel ,last15=Carling ,first15=David ,last16=Schuit ,first16=Frans C. ,last17=Birnbaum ,first17=Morris J. ,last18=Richter ,first18=Erik A. ,last19=Burcelin ,first19=Rémy ,last20=Vaulont ,first20=Sophie ,display-authors=5 ,date=January 2003 ,title=The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity ,url=http://www.jci.org/articles/view/16567 ,journal=The Journal of Clinical ...
cite journal ,last=Viollet ,first=Benoît ,last2=Andreelli ,first2=Fabrizio ,last3=Jørgensen ,first3=Sebastian B. ,last4=Perrin ,first4=Christophe ,last5=Geloen ,first5=Alain ,last6=Flamez ,first6=Daisy ,last7=Mu ,first7=James ,last8=Lenzner ,first8=Claudia ,last9=Baud ,first9=Olivier ,last10=Bennoun ,first10=Myriam ,last11=Gomas ,first11=Emmanuel ,last12=Nicolas ,first12=Gaël ,last13=Wojtaszewski ,first13=Jørgen F. P. ,last14=Kahn1 ,first14=Axel ,last15=Carling ,first15=David ,last16=Schuit ,first16=Frans C. ,last17=Birnbaum ,first17=Morris J. ,last18=Richter ,first18=Erik A. ,last19=Burcelin ,first19=Rémy ,last20=Vaulont ,first20=Sophie ,display-authors=5 ,date=January 2003 ,title=The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity ,url=http://www.jci.org/articles/view/16567 ,journal=The Journal of Clinical ...
Interleukin 15 receptor, alpha subunit is a subunit of the interleukin 15 receptor that in humans is encoded by the IL15RA gene. The IL-15 receptor is composed of three subunits: IL-15R alpha, CD122, and CD132. Two of these subunits, CD122 and CD132, are shared with the receptor for IL-2, but IL-2 receptor has an additional subunit (CD25). The shared subunits contain the cytoplasmic motifs required for signal transduction, and this forms the basis of many overlapping biological activities of IL15 and IL2, although in vivo the two cytokines have separate ...
Neutrophil cytosol factor 2 is a protein that in humans is encoded by the NCF2 gene. This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein complex known as NADPH oxidase found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease. GRCh38: Ensembl release 89: ENSG00000116701 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000026480 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: NCF2 ...
IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23α consisted of four exons and three introns; ... Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex. ... has proinflammatory properties related to IL-23R and IL-12Rβ1 receptor expression, and activates the JAK/STAT signaling pathway ... Moreover, IL-23α mRNA was more highly expressed than IL-12p40 and IL-12p35 mRNA in several organs of chickens infected with ...
Here, we show that IL-17, a cytokine that regulates granulopoiesis through G-CSF, is made by gammadelta T cells and ... Antibody blockade of the p40 subunit of IL-23 reduces neutrophil numbers in wild-type mice. These findings identify a major ... Interleukin-17 / immunology* * Interleukin-17 / metabolism * Interleukin-23 * Interleukin-23 Subunit p19 ... Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17 Immunity. 2005 Mar;22(3):285-94. doi: ...
... alpha subunit p19 ELISA Kits * Interleukin 24 ELISA Kits * Interleukin 25 ELISA Kits ... This ELISA antibody pair recognizes Mouse IL23. Characteristics *Strip plates and additional reagents allow for use in multiple ...
Il-6: Interleukin 6. Il23-p19: Interleukin 23, p19 subunit. Lcn2: Lipocalin 2 ... IL-6 and IL-23p19 (Figure 4A). LNCaP cells also upregulated LCN2, IL-6 and IL-23p19 transcription in response to treatment with ... Cell viability of all treatment groups was , 99%. (D) TC1.pNGL cells from (B) were also analyzed for Lcn2, Il-6, and Il-23p19 ... Validated FAM-labeled human IL-23A (Hs00372324_m1), IL-6 (Hs0098639_m1), HSPA5 (Hs99999174_m1), LCN2 (Hs00194353_m1), and VIC- ...
... mice lacking the p19 subunit necessary for formation of the cytokine were resistant to chemical carcinogenesis. Loss of IL-23 ... suggest that signaling by the cytokine interleukin 23 (IL-23) might provide an inroad to such a strategy. IL-23 has beneficial ... J. L. Langowski, X. Zhang, L. Wu, J. D. Mattson, T. Chen, K. Smith, B. Basham, T. McClanahan, R. A. Kastelein, M. Oft, IL-23 ... The authors found, however, that expression of IL-23 was increased in samples of human cancer tissues, and its role proved to ...
... which work by targeting the p40 subunit. However, the p40 subunit is also present in Interleukin 12 (IL-12) and causes serious ... Alphabody CMPX-1023 has been successfully developed to target the p19 subunit of Interleukin 23 (IL-23) and has entered ... In brief, IL-23 is a pro-inflammatory cytokine that has been implicated in autoimmune inflammatory diseases like psoriasis, ... Mouse studies and X-ray crystallography studies on IL-23 in complex with the Alphabody confirmed specific binding to p19 only. ...
IL12 and IL23 are heterodimeric cytokines, composed of a common IL12/23p40 subunit and a specific α-subunit (IL12p35 and ... Produced in large excess over p35 and p19 subunits, the p40 subunit also forms homodimers. The transcriptional activation of ... Interleukin (IL) 12 and IL23 are two related heterodimeric cytokines produced by antigen-presenting cells. The balance between ... Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 445:648-651. doi:10.1038/ ...
Binds to the p19 protein subunit of the interleukin (IL)-23 cytokine to prevent its interaction with the IL-23 receptor. This ... Binding to interleukins antagonizes their effects, inhibiting the release of proinflammatory cytokines and chemokines. ...
... is a heterodimeric cytokine that is related to IL-12 . It is composed of two disulfide-linked subunits, a p19 subunit that is… ... and a p40 subunit that is shared with IL-12 . The p19 subunit has homology to the p35 subunit of IL-12, as well as to other ... is a heterodimeric cytokine that is related to IL-12 . It is composed of two disulfide-linked subunits, a p19 subunit that is ... the IL-12 receptor .1 subunit (IL-12 R.1) and the IL-23-specific receptor subunit (IL-23 R) . IL-23 is produced by dendritic ...
... is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70. Infect. Immun. 70:1936. ... It consists of a helical cytokine subunit, p19, and a soluble receptor subunit, p40. The p40 subunit is promiscuous and can ... IL-12Rβ1) and the proprietary IL-23R chain (5). In parallel, IL-12 uses IL-12Rβ1 and the p35-specific IL-12Rβ2 chain (6) for ... neither IL-12 nor IL-4 induced IL-17 production by CD4+ cells, and thus it seems that IL-23 and IL-17 form a new axis through ...
Guselkumab is a human monoclonal antibody against the p19 subunit of interleukin (IL)-23, which is an important driver of the ... Developed by Janssen, guselkumab is a human monoclonal antibody against the p19 subunit of IL-23.2 Guselkumab was granted ... programme comprises the first-ever Phase 3 studies evaluating a human monoclonal antibody targeting the p19 subunit of IL-23 in ... If approved, guselkumab will be the first selective IL-23 p19 subunit inhibitor for people in the European Union with active ...
Tremfya is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits ... IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the ... IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the ...
Browse our IL-23A/IL-23 P19 Protein catalog backed by our Guarantee+. ... IL-23A/IL-23 P19 Proteins available through Novus Biologicals. ... alpha subunit p19 protein, interleukin-23 subunit alpha protein ... IL-23A protein, IL-23p19 protein, IL23P19P19 protein, interleukin 23 p19 subunit protein, interleukin 23, ... Our IL-23A/IL-23 P19 Peptides and IL-23A/IL-23 P19 Proteins can be used in a variety of model species: Human. Use the list ...
Interleukin 23 Subunit Alpha, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The ... IL23). IL23 is composed of this protein and the p40 subunit of interleukin 12 (IL12B). The receptor of IL23 is formed by the ... Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12 ... beta 1 subunit of IL12 (IL12RB1) and an IL23 specific subunit, IL23R. Both IL23 and IL12 can activate the transcription ...
... heterodimer composed of a p40 subunit identical to that of IL-12 and a unique p19 subunit that shares sequence homology with IL ... is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70. Infect. Immun. 70:1936-1948. ... mice show normal IL-17 and IL-17F induction but reduced IFN-γ. Lung IL-17 and IL-17F production in p19−/− mice was dramatically ... These data suggest that the absence of IL-17 signaling in p19−/− mice mediates the observed phenotype and that IL-17-induced IL ...
... a heterodimeric cytokine consisting of an unique p19 subunit and a p40 subunit that is shared with IL-12 (1, 2). IL-17A induces ... Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. ... Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12 ... Irradiated IL-17A−/− mice were transplanted with BM cells from wild-type (WT), IL-17A−/−, TCRCδ−/−, and both IL-17A−/− and TCRC ...
... that selectively targets the p19 subunit of interleukin (IL)-23, thereby inhibiting the IL-23/IL-17 axis, the signalling ...
Interleukin-6 (IL-6) is an immunoregulatory cytokine that activates a cell-surface signaling assembly composed of IL-6, the IL- ... p19) and a soluble class I cytokine receptor p40. IL-12 and IL-23 share p40 as an alpha-receptor subunit, yet show only 15% ... receptor subunits. Here we present the 2.8 angstrom crystal structure of a complex between human IL-2 and IL-2Ralpha, which ... IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R alpha/IL-13R alpha1/IL-13) ternary signaling complexes. The type I ...
P19, IL-23A, IL23p19) is a heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to IL ... p19/p40) ELISA Kit with Pre-coated Plates - Mouse IL-23 (Interleukin 23 p19/p40, ... and a p40 subunit that is shared with IL-12. ... Interleukin 23 p19/p40, P19, IL-23A, IL23p19) is a ... heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to IL-23, and a p40 subunit that ...
Tildrakizumab, a high-affinity humanized IgG1k antibody that selectively binds interleukin (IL)-23 p19 subunit of cytokine IL- ... In critically ill patients, artificial feeding by tubes need t.... Alzheimers Disease Of all the types of Dementia, ... Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, Following Intravenous or Subcutaneous ... 23 and neutralizes its function, is under investigation for treatment of m... ...
Tildrakizumab, a high-affinity humanized IgG1k antibody that selectively binds interleukin (IL)-23 p19 subunit of cytokine IL- ... Pharmacokinetics of Tildrakizumab (MK-3222), an Anti-IL-23 Monoclonal Antibody, Following Intravenous or Subcutaneous ... after continuous intravenous infusion and subcutaneous dosing of enoxaparin for thromboprophylaxis in critically ill patients. ... 23 and neutralizes its function, is under investigation for treatment of m... ...
Guselkumab is a human monoclonal IgG1? antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and ... IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. In October 2010, Kyowa Hakko Kirin licensed from Kirin-Amgen exclusive rights ... Skyrizi (Risankizumab) is a humanized IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this ... Lumicef (Brodalumab) is a human interleukin-17 receptor A (IL-17RA) antagonist being marketed by Kyowa Hakko Kirin in Japan for ...
... is a humanized lgG1/k monoclonal antibody designed to selectively bind to the p19 subunit of interleukin-23 (IL-23) and inhibit ... IL-23) inhibitor approved for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic ... its interaction with the IL-23 receptor, leading to inhibition of the release of pro-inflammatory cytokines and chemokines. ...
... comprising an IL-12/IL-23p40 subunit and a p19 subunit, interacts with its receptor IL-23R (composed of IL-23R and IL12R-β1) to ... Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. ... IL-23R), IL-12/IL-23p40 subunit, RORγt, and IL-17A mRNA increased more gradually, peaking 7 days post-MI. Expression of IL-17 ... IL-23R), RORγt, IL-17A, and IL-17 receptor A (IL-17RA) in heart tissue after MI. The levels of each transcript were normalized ...
"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12 ... IL-12B is a common subunit of interleukin 12 and Interleukin 23. This gene encodes a subunit of interleukin 12, a cytokine that ... Subunit beta of interleukin 12 (also known as IL-12B, natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation ... Interleukin-12 p40 also serves as a subunit of Interleukin 23. GRCh38: Ensembl release 89: ENSG00000113302 - Ensembl, May 2017 ...
  • Collectively, these results indicate that ChIL-23 is a member of the IL-12 family, has proinflammatory properties related to IL-23R and IL-12Rβ1 receptor expression, and activates the JAK/STAT signaling pathway that results in the interaction of ChIL-23α with ChIL-12p40 to form the novel ChIL-23 complex. (ovid.com)
  • Even though IL\23 signaling pathway is definitely implicated both in RA and PsA, its participation within the pathogenesis of the disorders could be different as confirmed by clinical research where concentrating on IL\23 provides different final results 14, 15. (research-matters.net)
  • Herein, we explored the role of the adenine and uridine-rich element (ARE)-binding protein tristetraprolin (TTP) in influencing mRNA stability of IL12p35, IL12/23p40, and IL23p19 subunits. (rupress.org)
  • In contrast, we observed a strong impact of TTP on IL23 production and IL23p19 mRNA stability through several AREs in the 3′ untranslated region. (rupress.org)
  • Furthermore, analysis of dendritic cell mediators responsible for a proinflammatory differentiation of T cells revealed a significant reduction of IL-12p70 and IL23p19 as well as IL-6 and IL-17. (aspetjournals.org)
  • Finally, Prof Girolomoni reviewed the indications for biologic therapies and discussed how IL-23 inhibitors can be integrated into the current therapeutic environment. (emjreviews.com)
  • In addition, the NF-kappaB and the AP-1 inhibitors down-regulated the expression of IL-23 p19 mRNA induced by IL-1beta. (qxmd.com)
  • The use of IL-12/IL-23 inhibitors, such as ustekinumab, is now also possible in Crohn's disease (CD), providing another example of the successful translation of immunological targeting into clinical practice. (schnitzeljagd2014.info)
  • On the other hand, PASI 75 and PASI 90 response achieved by tildrakizumab in the phase II and III trials are less than the response achieved by the IL-17A inhibitors and other p19 competitors, possibly due to a less intensive dosing regimen, although direct comparisons cannot be made without a head-to-head randomized clinical trial. (qxmd.com)
  • 35 , 36 Analysts expect ixekizumab to be used as second- or third-line therapy after TNF failure, competing with secukinumab, another IL-17 inhibitor. (ptcommunity.com)
  • Recently, the creation of IL-23 p19 −/− mice has shown that IL-23 is critical for the generation of memory T cell-dependent humoral and cell-mediated immune responses to antigen ( 16 ). (rupress.org)
  • Here, we examined the role of IL-23 in the non-autoimmune antigen-induced arthritis (AIA) model. (biomedcentral.com)
  • Antigen-induced arthritis was induced in wild-type, IL-23p19-deficient and IL-17 Receptor A - knockout mice. (biomedcentral.com)
  • Here, our results revealed that IL-23 is essential for the development of full-blown antigen-induced arthritis. (biomedcentral.com)
  • Interleukin-2 (IL-2) is a O-glycosylated, four alpha -helix bundle cytokine that has potent stimulatory activity for antigen-activated T cells. (rndsystems.com)
  • Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. (semanticscholar.org)
  • Puccetti PBelladonna MLGrohmann U Effects of IL-12 and IL-23 on antigen-presenting cells at the interface between innate and adaptive immunity. (jamanetwork.com)
  • A study of the IL-23 risankizumab in active ankylosing spondylitis (AS) patients failed to show efficacy and did not meet primary efficacy endpoints in a 6-month trial. (rheumnow.com)
  • NORTH CHICAGO, Ill., Feb. 17, 201 8 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global research and development-based biopharmaceutical company, today presented new positive results from the pivotal Phase 3 ultIMMa -1 and ultIMMa -2 replicate clinical trials that evaluated the safety and efficacy of risankizumab (150 mg) compared to placebo or ustekinumab (45 or 90 mg, based on patient weight). (psoriasiscouncil.org)
  • Both IL23 and IL12 can activate the transcription activator STAT4, and stimulate the production of interferon-gamma (IFNG). (genecards.org)
  • At days 1 and 7 of AIA, splenocytes and joint-infiltrating cells were isolated and analyzed for intracellular IL-17A and interferon (IFN)-γ ex-vivo by flow cytometry. (biomedcentral.com)
  • Initially, the pathogenic mechanism was thought to be based on the upregulation of interferon (IFN)-γ and interleukin (IL)-12, signaling, with both cluster of differentiation (CD)4+ and CD8+ IFN-γ-producing T cells (named Th1 and Tc1 cells, respectively) as key players [ 6 , 7 ]. (mdpi.com)
  • Early studies of T-cell cytokine production in RA indicated that synovial T cells produce low levels of interleukin (IL) 2 and interferon gamma (IFNγ). (bmj.com)
  • 1-3 T helper 17 (Th17) cells are a functional lymphocyte subset that has developed to co-ordinate the immune response against bacterial and fungal infections and are characterised by the production of IL-17, IL-22, and interferon (IFN)-γ. (schnitzeljagd2014.info)
  • Traditionally, CD lesion has been associated with a predominant activation of T helper type 1 (Th1)-lymphocytes that produce large quantities of interferon (IFN)- under the stimulus of interleukin (IL)-12 [ 5 - 7 ]. (hindawi.com)
  • Moreover, IL-23α mRNA was more highly expressed than IL-12p40 and IL-12p35 mRNA in several organs of chickens infected with Salmonella. (ovid.com)
  • Moreover, IL-23 up-regulated the IL-8 and IL-6 mRNA and protein levels in a dose-dependent manner in HFLS-RA. (qxmd.com)
  • PHA effected an increase of p19 mRNA in both CD4+ and CD8+ T cells, whereas p35 was minimally regulated by PHA. (nih.gov)
  • p19 mRNA was detectable in most hematopoietic cell lines tested but p35 distribution was more restricted. (nih.gov)
  • Because of its ability to activate STAT-4, as well as its ability to stimulate IFN-γ production by human T cells, IL-23 was initially recognized as similar to IL-12, with the important distinction that its actions appear to be restricted to a subset of CD4 + cells bearing markers characteristic for memory and/or regulatory cells ( 1 , 20 ). (jimmunol.org)
  • In addition, to its ability to covalently bind to p35 to form IL-12, p40 can bind to p19 to form IL-23. (sbhsciences.com)
  • This is due to the presence of monomer and dimer forms of p40, while only a small portion associates with p19 to form IL-23. (fishersci.co.uk)
  • IL12 and IL23 play crucial and distinct roles in shaping the innate and adaptive immune responses against invading pathogens. (rupress.org)
  • IL-23 has beneficial effects in promoting immune responses to bacterial infections. (sciencemag.org)
  • Thus, IL-23 plays a critical role in T cell-dependent immune responses, and our data provide further support for the existence of an IL-23/IL-17 axis of communication between the adaptive and innate parts of the immune system. (jimmunol.org)
  • The contributions of C5a interaction with its receptors in the production of IL-17/IL-23 and promotion of IL-17-dependent immune responses are reviewed. (frontiersin.org)
  • The biology of IL-12: coordinating innate and adaptive immune responses. (jamanetwork.com)
  • IL-23 plays a role in type 1-polarized T-cell immune responses. (biovendor.com)
  • Interestingly, the development of Th17 cells was inhibited by IFN-γ and IL-4. (jimmunol.org)
  • However, newer studies have revealed that IL-23 stimulates and promotes differentiation in a subset of memory-activated CD4+ T-cells known as Th17 cells [ 8 , 9 , 10 , 11 ]. (escholarship.org)
  • Although structurally much like IL\12, IL\23 gets the exclusive capability of amplifying and stabilizing the proliferation of IL\17 secreting Rocuronium bromide T helper\17 (Th17) cells 3. (research-matters.net)
  • Actually, publicity of Th17 cells to IL\23 drives Rocuronium bromide their pathogenic phenotype 4, 5. (research-matters.net)
  • IL-23 is involved in regulating Th17 cells and is a potent activator of keratinocyte proliferation. (qxmd.com)
  • Th17 cells have derived the name by their ability to produce IL-17, also termed IL-17A. (hindawi.com)
  • induction of Th17 cells does not require IL-17A [ 14 ]. (hindawi.com)
  • Importantly, IL-21 stimulates Th17 cells to produce IL-21, thus triggering an autocrine loop that amplifies Th17 cell responses [ 24 ]. (hindawi.com)
  • We demonstrate that the clinical and immunological parameters associated with TTP deficiency were completely dependent on the IL23-IL17A axis. (rupress.org)
  • Deleterious Effect of the IL-23/IL-17A Axis and γδT Cells on Left Ventricular Remodeling After Myocardial Infarction. (biomedsearch.com)
  • METHODS AND RESULTS: We created a large MI by permanent ligation of the coronary artery and identified a potential link between the interleukin (IL)-23/IL-17A axis and γδT cells that affects late-stage LV remodeling after MI. (biomedsearch.com)
  • The importance of the IL-23/IL-17 axis was further confirmed using IL-17 Receptor A knockout mice showing significantly milder AIA compared to control mice, with a disease course comparable to that of IL-23p19-deficient mice. (biomedcentral.com)
  • The IL\23/Th17 axis continues to be implicated within the development of autoimmune illnesses, such as arthritis rheumatoid (RA) and psoriatic arthritis (PsA). (research-matters.net)
  • Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. (ox.ac.uk)
  • Adoptive transfer of wild-type, but not adhesion molecule-deficient, neutrophils into mice deficient in beta2 integrins transiently decreases neutrophilia and reduces levels of serum IL-17. (nih.gov)
  • Instead, mice lacking the p19 subunit necessary for formation of the cytokine were resistant to chemical carcinogenesis. (sciencemag.org)
  • Transplanted tumors grew more poorly in mice that lacked functional IL-23 or its receptor. (sciencemag.org)
  • Previously reported IL-12p40-deficient mice have profound immune defects resulting from combined deficiency in both IL-12 and IL-23. (jimmunol.org)
  • IL-23p19 −/− mice produce strongly reduced levels of Ag-specific Igs of all isotypes, but mount normal T-independent B cell responses. (jimmunol.org)
  • T cells stimulated with IL-23-deficient APCs secrete significantly reduced amounts of the proinflammatory cytokine IL-17, and IL-23-deficient mice phenotypically resemble IL-17-deficient animals. (jimmunol.org)
  • In mice, IL-12p40 is also found as a homodimer (p40 2 ), which antagonizes IL-12 and likely also IL-23 through nonproductive binding of IL-12Rβ1 ( 2 , 7 ). (jimmunol.org)
  • Many of the biological effects of IL-12 have been deduced either from the phenotype of mice that lack p40 or from experiments with p40-specific inhibitory Abs. (jimmunol.org)
  • For example, it was shown that IL-12p40 −/− mice have reduced NK cell responses, reduced delayed-type hypersensitivity (DTH) 3 responses, and deficient Th-type 1 (Th1) development ( 8 ). (jimmunol.org)
  • Through the discovery of IL-23, however, it became apparent that these mice suffer from the combined loss of IL-23 and IL-12. (jimmunol.org)
  • Indeed, IL-12p35 −/− mice, which lack only IL-12, but not IL-23, and are less well characterized, display only some, but not all, phenotypes of IL-12p40 −/− mice ( 9 , 10 ). (jimmunol.org)
  • We show that IL-12/23 p40-deficient mice are exquisitely sensitive to intrapulmonary K. pneumoniae inoculation and that IL-23 p19 − / − , IL-17R − / − , and IL-12 p35 − / − mice also show increased susceptibility to infection. (rupress.org)
  • p40 − / − mice fail to generate pulmonary IFN- γ , IL-17, or IL-17F responses to infection, whereas p35 − / − mice show normal IL-17 and IL-17F induction but reduced IFN- γ . (rupress.org)
  • Lung IL-17 and IL-17F production in p19 − / − mice was dramatically reduced, and this strain showed substantial mortality from a sublethal dose of bacteria (10 3 CFU), despite normal IFN- γ induction. (rupress.org)
  • Administration of IL-17 restored bacterial control in p19 − / − mice and to a lesser degree in p40 − / − mice, suggesting an additional host defense requirement for IFN- γ in this strain. (rupress.org)
  • In the present report, we demonstrate that IL-17A is expressed in the liver of mice infected with Listeria monocytogenes from an early stage of infection. (jimmunol.org)
  • IL-17A is important in protective immunity at an early stage of listerial infection in the liver because IL-17A-deficient mice showed aggravation of the protective response. (jimmunol.org)
  • Despite the finsinf that infarct size 24 hours after surgery was similar to that in wild-type mice, a deficiency in IL-23, IL-17A, or γδT cells improved survival after 7 days, limiting infarct expansion and fibrosis in noninfarcted myocardium and alleviating LV dilatation and systolic dysfunction on day 28 post-MI. (biomedsearch.com)
  • Both IL-17 knockout mice and humans with a genetic IL-17 deficiency are susceptible to extracellular and intracellular pathogens. (escholarship.org)
  • Depletion of IL-17A-producing Vγ4 + TCRγδ + T cells resulted in a significant reduction of the clinical disease score although mice were not fully protected [ 14 ]. (biomedcentral.com)
  • Th17 differentiation can be induced by IL-21 in IL-6-deficient mice [ 23 ]. (hindawi.com)