A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
A pattern recognition receptor that forms heterodimers with TLR2 RECEPTOR. The complex interacts with a variety of ligands including LIPOPROTEINS from MYCOPLASMA.
A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.
A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES.
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.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
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.
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)
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.
Drugs that bind to and activate dopamine receptors.
Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.
A dopamine D2/D3 receptor agonist.
Compounds with BENZENE fused to AZEPINES.
A selective D1 dopamine receptor agonist used primarily as a research tool.
A serotonin receptor antagonist in the CENTRAL NERVOUS SYSTEM used as an antipsychotic.
A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.
A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation.
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.
A subtype of dopamine D1 receptors that has higher affinity for DOPAMINE and differentially couples to GTP-BINDING PROTEINS.
A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.
Amides of salicylic acid.
Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.
A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy.
A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)
A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.
Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.
A spiro butyrophenone analog similar to HALOPERIDOL and other related compounds. It has been recommended in the treatment of SCHIZOPHRENIA.
A subtype of dopamine D2 receptors that has high affinity for the antipsychotic CLOZAPINE.
An antipsychotic agent that is specific for dopamine D2 receptors. It has been shown to be effective in the treatment of schizophrenia.
A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.
A butyrophenone with general properties similar to those of HALOPERIDOL. It has been used in the treatment of aberrant sexual behavior. (From Martindale, The Extra Pharmacopoeia, 30th ed, p567)
A pattern recognition receptor that binds DOUBLE-STRANDED RNA. It mediates cellular responses to certain viral pathogens.
A vessel that directly interconnects an artery and a vein, and that acts as a shunt to bypass the capillary bed. Not to be confused with surgical anastomosis, nor with arteriovenous fistula.
A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to the GQ-G11 G-PROTEINS resulting in increased intracellular levels of INOSITOL PHOSPHATES and free CALCIUM.
Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.
Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.
A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor (see RECEPTORS, DOPAMINE D2) antagonist.
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.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A pattern recognition receptor that binds FLAGELLIN. It mediates cellular responses to certain bacterial pathogens.
A pattern recognition receptor that binds several forms of imidazo-quinoline including the antiviral compound Imiquimod.
A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Cytosolic signaling adaptor proteins that were initially discovered by their role in the innate immunity (IMMUNITY, INNATE) response of organisms that lack an adaptive immune system. This class of proteins contains three domains, a C-terminal ligand recognition domain, an N-terminal effector-binding domain, and a centrally located nuclear-binding oligomerization domain. Many members of this class contain a C-terminal leucine rich domain which binds to PEPTIDOGLYCAN on the surface of BACTERIA and plays a role in pathogen resistance.
Glycoproteins found on the membrane or surface of cells.
A pattern recognition receptor that recognizes GUANOSINE and URIDINE-rich single-stranded RNA.
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.
N-methyl-8-azabicyclo[3.2.1]octanes best known for the ones found in PLANTS.
A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
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.
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.
Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.
A dopamine D2 agonist. It is used in the treatment of parkinson disease, particularly for alleviation of tremor. It has also been used for circulatory disorders and in other applications as a D2 agonist.
Established cell cultures that have the potential to propagate indefinitely.
Interferon inducer consisting of a synthetic, mismatched double-stranded RNA. The polymer is made of one strand each of polyinosinic acid and polycytidylic acid.
The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.
A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.
A large family of cell surface receptors that bind conserved molecular structures (PAMPS) present in pathogens. They play important roles in host defense by mediating cellular responses to pathogens.
A family of intracellular signaling kinases that were identified by their ability to signal from the activated INTERLEUKIN-1 RECEPTORS. Signaling from these kinases involves their interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88 and TNF RECEPTOR-ASSOCIATED FACTOR 6.
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)
The observable response an animal makes to any situation.
A vasoconstrictor found in ergot of Central Europe. It is a serotonin agonist that has been used as an oxytocic agent and in the treatment of MIGRAINE DISORDERS.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
Proteins found in any species of insect.
Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.
An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.
An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.
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.
The amount of PLASMA that perfuses the KIDNEYS per unit time, approximately 10% greater than effective renal plasma flow (RENAL PLASMA FLOW, EFFECTIVE). It should be differentiated from the RENAL BLOOD FLOW; (RBF), which refers to the total volume of BLOOD flowing through the renal vasculature, while the renal plasma flow refers to the rate of plasma flow (RPF).
A pattern recognition receptor that is expressed in LUNG and in B-LYMPHOCYTES.
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.
The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.
Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.
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.
A group of compounds that contain the structure SO2NH2.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A mitosporic fungal genus. Teleomorphs are found in the family Clavicipitaceae and include Cordyceps bassiana. The species Beauveria bassiana is a common pathogen of ARTHROPODS and is used in PEST CONTROL.
A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.
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).
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
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.)
A large family of RNA helicases that share a common protein motif with the single letter amino acid sequence D-E-A-D (Asp-Glu-Ala-Asp). In addition to RNA helicase activity, members of the DEAD-box family participate in other aspects of RNA metabolism and regulation of RNA function.
Hormones secreted by insects. They influence their growth and development. Also synthetic substances that act like insect hormones.
A NOD-signaling adaptor protein that contains a C-terminal leucine-rich domain which recognizes bacterial PEPTIDOGLYCAN. It signals via an N-terminal caspase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. It plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM.
The physical activity of a human or an animal as a behavioral phenomenon.
Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.
Portion of midbrain situated under the dorsal TECTUM MESENCEPHALI. The two ventrolateral cylindrical masses or peduncles are large nerve fiber bundles providing a tract of passage between the FOREBRAIN with the HINDBRAIN. Ventral MIDBRAIN also contains three colorful structures: the GRAY MATTER (PERIAQUEDUCTAL GRAY), the black substance (SUBSTANTIA NIGRA), and the RED NUCLEUS.
A genus of beetles which infests grain products. Its larva is called mealworm.
New World marsupials of the family Didelphidae. Opossums are omnivorous, largely nocturnal and arboreal MAMMALS, grow to about three feet in length, including the scaly prehensile tail, and have an abdominal pouch in which the young are carried at birth.
A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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 NOD signaling adaptor protein that contains two C-terminal leucine-rich domains which recognize bacterial PEPTIDOGLYCAN. It signals via an N-terminal capase recruitment domain that interacts with other CARD SIGNALING ADAPTOR PROTEINS such as RIP SERINE-THEONINE KINASES. The protein plays a role in the host defense response by signaling the activation of CASPASES and the MAP KINASE SIGNALING SYSTEM. Mutations of the gene encoding the nucleotide oligomerization domain 2 protein have been associated with increased susceptibility to CROHN DISEASE.
The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.
A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.
The ability of the BRAIN to suppress neuronal responses to external sensory inputs, such as auditory and visual stimuli. Sensory filtering (or gating) allows humans to block out irrelevant, meaningless, or redundant stimuli.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
BENZOIC ACID amides.
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.
Compounds consisting of a short peptide chain conjugated with an acyl chain.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
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.
The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)
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.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signalling and activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES.
Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
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.
Sodium excretion by URINATION.
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.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed)
A series of structurally-related alkaloids that contain the ergoline backbone structure.
The largest and most lateral of the BASAL GANGLIA lying between the lateral medullary lamina of the GLOBUS PALLIDUS and the EXTERNAL CAPSULE. It is part of the neostriatum and forms part of the LENTIFORM NUCLEUS along with the GLOBUS PALLIDUS.
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.
The blood/lymphlike nutrient fluid of some invertebrates.
A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).
The interactions between a host and a pathogen, usually resulting in disease.
Elements of limited time intervals, contributing to particular results or situations.
The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Activities performed to obtain licit or illicit substances.
A serotonin receptor subtype found at high levels in the BASAL GANGLIA and the frontal cortex. It plays a role as a terminal autoreceptor that regulates the rate of SEROTONIN release from nerve endings. This serotonin receptor subtype is closely related to and has similar drug binding properties as the 5-HT1D RECEPTOR. It is particularly sensitive to the agonist SUMATRIPTAN and may be involved in mediating the drug's antimigraine effect.
The function of opposing or restraining the excitation of neurons or their target excitable cells.
Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).
A species of gram-positive, spherical bacteria whose organisms occur in tetrads and in irregular clusters of tetrads. The primary habitat is mammalian skin.
Multiprotein complexes that mediate the activation of CASPASE-1. Dysregulation of inflammasomes has also been linked to a number of autoinflammatory and autoimmune disorders.
The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)
A phosphoprotein that was initially identified as a major target of DOPAMINE activated ADENYLYL CYCLASE in the CORPUS STRIATUM. It regulates the activities of PROTEIN PHOSPHATASE-1 and PROTEIN KINASE A, and it is a key mediator of the biochemical, electrophysiological, transcriptional, and behavioral effects of DOPAMINE.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters.
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.
Nerve fibers liberating acetylcholine at the synapse after an impulse.
An interferon regulatory factor that is expressed constitutively and undergoes POST-TRANSLATIONAL MODIFICATION following viral infection. PHOSPHORYLATION of IRF-3 causes the protein to be translocated from the CYTOPLASM to CELL NUCLEUS where it binds DNA, and activates transcription.
The nonstriated involuntary muscle tissue of blood vessels.
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
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.
A nutritional reservoir of fatty tissue found mainly in insects and amphibians.
The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus.
The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin.
The emission of SEMEN to the exterior, resulting from the contraction of muscles surrounding the male internal urogenital ducts.
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.
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.
A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.
Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.
A region in the MESENCEPHALON which is dorsomedial to the SUBSTANTIA NIGRA and ventral to the RED NUCLEUS. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the NUCLEUS ACCUMBENS. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of SCHIZOPHRENIA.
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.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity.
Drugs used to cause constriction of the blood vessels.
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.
Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.
A genus of the family CEBIDAE consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies.
Use of electric potential or currents to elicit biological responses.
Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced.
A family of hexahydropyridines.
Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.
A purinergic P2X neurotransmitter receptor that plays a role in pain sensation signaling and regulation of inflammatory processes.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
Disorders related or resulting from use of cocaine.
Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.
The processes occurring in early development that direct morphogenesis. They specify the body plan ensuring that cells will proceed to differentiate, grow, and diversify in size and shape at the correct relative positions. Included are axial patterning, segmentation, compartment specification, limb position, organ boundary patterning, blood vessel patterning, etc.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
Refers to animals in the period of time just after birth.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The functional hereditary units of INSECTS.
A protein with a molecular weight of 40,000 isolated from bacterial flagella. At appropriate pH and salt concentration, three flagellin monomers can spontaneously reaggregate to form structures which appear identical to intact flagella.
Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms.
Wave-like oscillations of electric potential between parts of the brain recorded by EEG.
The strengthening of a conditioned response.
A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR).
"Entrez Gene: TLR4 toll-like receptor 4". Tidswell M, Tillis W, Larosa SP, Lynn M, Wittek AE, Kao R, et al. (January 2010). " ... Toll-like receptor 4 (TLR4) detects lipopolysaccharides found in most Gram-negative bacteria. Because of its similarity to the ... Toll-like receptors (TLRs) play an important role in the innate immune system. They recognise microbes and activate ... role of MD2/TLR4 PTMs on receptor function is not fully understood, recruitment of heterogeneous patient population, and lack ...
ATIs may cause toll-like receptor 4 (TLR4)-mediated intestinal inflammation in humans. People can also experience adverse ... "Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4". Journal of Experimental ... This permeating effect is secondary to the binding of specific undigestible gliadin fragments to the CXCR3 chemokine receptor ... 128 (4 Suppl 1): S68-73. doi:10.1053/j.gastro.2005.02.015. PMID 15825129. Elli L, Branchi F, Tomba C, Villalta D, Norsa L, ...
The protein encoded by this gene is involved in binding lipopolysaccharide with Toll-Like Receptor (TLR4). The MD-2 protein ... Abreu MT, Vora P, Faure E, Thomas LS, Arnold ET, Arditi M (August 2001). "Decreased expression of Toll-like receptor-4 and MD-2 ... Ohnishi T, Muroi M, Tanamoto K (May 2003). "MD-2 is necessary for the toll-like receptor 4 protein to undergo glycosylation ... Dziarski R, Wang Q, Miyake K, Kirschning CJ, Gupta D (February 2001). "MD-2 enables Toll-like receptor 2 (TLR2)-mediated ...
"Toll-like receptors (TLR2 and TLR4) recognize polysaccharides of Pseudallescheria boydii cell wall". Carbohydrate Research. 356 ... Immune response is characterized by TLR2 recognition of P. boydii derived α-glucans, while TLR4 mediates the recognition of P. ... 37 (3-4): 71-8. doi:10.1111/j.1439-0507.1994.tb00780.x. PMID 7845423. Figueiredo, Rodrigo Tinoco; Bittencourt, Vera Carolina B ... 62 (4): 727-740. doi:10.2307/3757662. JSTOR 3757662. McGinnis, M.R.; Padhye, A.A.; Ajello, L. (1982). "Pseudallescheria Negroni ...
January 2010). "Evidence that opioids may have toll-like receptor 4 and MD-2 effects". Brain, Behavior, and Immunity. 24 (1): ... This receptor is involved in immune system responses, and activation of TLR4 induces glial activation and release of ... July 2008). "Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 ( ... May 2010). "Possible involvement of toll-like receptor 4/myeloid differentiation factor-2 activity of opioid inactive isomers ...
Toll-like Receptor-4 (TLR4) Down-regulates MicroRNA-107, Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6.» J Biol ... TLR4) Down-regulates MicroRNA-107, Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6." (2011) His scientific career ... Klein R, Jing SQ, Nanduri V, O'Rourke E, Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell ... Lamballe F, Klein R, Barbacid M. «trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for ...
TLR4-IN-C34 Resatorvid VGX-1027 Nakamura M, Shimizu Y, Sato Y, Miyazaki Y, Satoh T, Mizuno M, et al. (August 2007). "Toll-like ... M62812 is a drug which acts as a potent and selective antagonist of toll-like receptor 4 (TLR4). In animal studies it blocks ... October 2020). "TAP2, a peptide antagonist of Toll-like receptor 4, attenuates pain and cartilage degradation in a ... TLR4-mediated cytokine release and has antiinflammatory effects, showing efficacy in animal models of arthritis and septic ...
... as the LPS receptor Toll-like Receptor 4 (TLR4) cannot recognise LPS while aggregated. Monomeric LPS is then transferred to MD- ... Vascular endothelial cells also express TLR4 and MD-2 and so respond to LPS directly, as well as via cytokines and nitric oxide ... Bronchial epithelial cells and colonic epithelial cells also express TLR4, but as they do not express MD-2 they rely on LPS ... 2 pre-complexed with TLR4 on macrophages and monocytes. This leads to release of pro-inflammatory cytokines and nitric oxide, ...
Cell survival signalling can also be mediated by TLR-3 (toll-like receptors) and TLR-4. In here, RIPK1 is recruited to the ... ligand to its membrane receptor, the TNFR (tumor necrosis factor receptor). Once activated, the intracellular domain of TNFR ... The death domain is homologous to the DD of other receptors such as Fas, TRAILR2 (DR5), TNFR1 and TRAILR1 (DR4), so it can bind ... It has been observed that RIPK1 may also interact with IGF-1R (insulin-like growth factor 1 receptor) to activate JNK (c-Jun N- ...
One type of PRR is a group of integral membrane glycoproteins called toll-like receptors (TLRs), which can recognize certain ... TLR2, TLR4, and TLR9 polymorphisms and Chron's disease in a New Zealand Caucasian cohort. 2007. Journal of Gastroenterology and ... Evidence for association between a Toll-like receptor 4 gene polymorphism and moderate to severe periodontitis in the Japanese ... A receptor on one cell surface binds to its specific ligand on a nearby cell, initiating a cascade of events which regulate ...
"Distinct Roles for APPL1 and APPL2 in Regulating Toll-like Receptor 4 Signaling in Macrophages: APPL Regulation of TLR4 ... 2014). "Rab8a interacts directly with PI3Kγ to modulate TLR4-driven PI3K and mTOR signalling" (PDF). Nature Communications. 5: ... 46 (4): 1004-1010. doi:10.1002/eji.201545943. PMID 27062120. "Professor Jennifer Stow". imb.uq.edu.au. 2019-07-25. Retrieved ...
... demonstrating that one of the mammalian Toll-like receptors, TLR4, acts as the membrane-spanning component of the mammalian LPS ... Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine ... The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nature ... From Endotoxin to the Toll-like Receptors Nobel Prize Inspiration Initiative Scientific Publications - All publications of ...
ATIs are part of the plant's natural defence against insects and may cause toll-like receptor 4 (TLR4)-mediated intestinal ... Our finding of ATI as a potent stimulator of TLR4 in the intestine might not only be relevant to celiac disease, but is likely ... "Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4". Journal of Experimental ... "Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4". Journal of Experimental ...
... the toll-like receptors, the C-type lectin receptors, the NOD-like receptors, and the RIG-I-like receptors. Invariably, the ... showed that TLR4 was the sole candidate locus within the Lps critical region; this strongly implied that a mutation within TLR4 ... These observations were finally linked in 1998 by the discovery of the toll-like receptor gene 4 (TLR 4). Genetic mapping work ... However, β2 adrenergic receptor agonists are not recommended to treat ARDS because it may reduce survival rates and precipitate ...
ATIs are part of the plant's natural defense against insects and may cause toll-like receptor 4 (TLR4)-mediated intestinal ... These TLR4-stimulating activities of ATIs are limited to gluten-containing cereals. A 2017 study in mice demonstrated that ATIs ... "Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4". Journal of Experimental ... Retrieved 4 June 2020. Smith, Oliver; Momber, Garry; et al. (2015). "Sedimentary DNA from a submerged site reveals wheat in the ...
... is principally a PDE4 inhibitor but has also been shown to act as an antagonist at the toll-like receptor 4 (TLR4). ... TLR4 antagonists theoretically reverse the increase in pain and inflammation caused by most TLR4 agonists, which includes ... Jia ZJ, Wu FX, Huang QH, Liu JM (April 2012). "[Toll-like receptor 4: the potential therapeutic target for neuropathic pain]". ... January 2010). "Evidence that opioids may have toll-like receptor 4 and MD-2 effects". Brain, Behavior, and Immunity. 24 (1): ...
TLR4) and the receptor for advanced glycation end products. Altered expression of the S100A9 protein is associated with the ... "Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock". Nat. Med. 13 (9 ... MRP8 and MRP14 regulate myeloid cell function by binding to Toll-like receptor 4 ( ... "S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products". ...
... (and LPS) has been demonstrated to activate cells via Toll-like receptor 4 (TLR4), MD-2 and CD14 on the cell surface. ... The ability of TLR4/MD-2 system to respond to a distinct lipid A species are clinically important. Pathogenic bacteria may ... 2010). "Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis". ... "Structural Relationship of the Lipid A Acyl Groups to Activation of Murine Toll-Like Receptor 4 by Lipopolysaccharides from ...
Toll-like Receptor 4 (TLR4). The enzyme's 2 disulfide-linked subunits are encoded by a single mRNA. The smaller subunit is a ... 4 (3): 293-302. doi:10.1016/j.chom.2008.06.009. PMC 2607035. PMID 18779055. Lu M, Varley AW, Munford RS (2013). "Persistently ...
Lectin-like ox-LDL receptor-1 (LOX-1) - toll-like receptor 4 (TLR4) interaction and autophagy in CATH.a differentiated cells ... His current research is on the uptake of oxidized low density lipoprotein (LDL) by specialized receptors LOX-1 (OLR1). Mehta ... Critical role of AT1 receptor expression after ischemia-reperfusion in isolated rat hearts: Beneficial effect of antisense ... His work on LOX-1 receptors, its polymorphic variants and its role in atherogenesis and myocardial ischemia has led to new ...
"First in Human Study of an Anti-Toll-like Receptor 4 (TLR4) Monoclonal Antibody (NI-0101) in Adult Healthy Volunteers - Full ... Novimmune has six publicly disclosed drug in their pipeline: NI-0101, an anti-TLR4 antibody being developed in partnership with ... ". "Pipeline - NI-0101 anti-TLR4". www.novimmune.com. "NI-0401 in Patients With Acute Renal Allograft Rejection - Full Text ...
In addition, toll-like receptor 4 (TLR4 ) normally recognizes pathogens and begins a signalling cascade to induce production of ... In cells infected with C. canimorsus, TLR4 did not activate the signalling pathway, so did not elicit an inflammatory response ... Symptoms may appear within 2-3 days after exposure, or up to 4 weeks later. Middle-aged and elderly persons are at greater risk ...
2015). "Structural Relationship of the Lipid A Acyl Groups to Activation of Murine Toll-Like Receptor 4 by Lipopolysaccharides ... The ability of TLR4 to respond to a distinct LPS species are clinically important. Pathogenic bacteria may employ LPS with low ... "Toll-like receptor" protein 4 (TLR-4). This signaling results in the activation of nuclear factor kappaB (NF-κB), which leads ... The effects of the cytokines may be amplified by TLR-4 engagement on endothelial cells. In response to inflammation, a ...
Classic examples of PRRs include toll-like receptors (TLRs) and NOD-like receptors (NLRs). Recognition of PAMPs and DAMPs ... TLR4). In 2015, gasdermin D (GSDMD) was identified as the effector of pyroptosis that permeabilizes the cell membrane. In 2021 ... can trigger pyroptosis and subsequent inflammatory responses independent of toll-like receptor 4 ( ... These receptors upregulate expression of inflammatory cytokines such as IFN α/β, tumour necrosis factor (TNF), IL-6 and IL-12 ...
... such as Toll Like Receptor 4 (TLR4) which recognize MAMPs. MAMPs, also known as PAMPs, are microbial associated molecular ... Alpha-MSH is a cleavage product of ACTH that has an equal affinity for the MC1 receptor on melanocytes as ACTH. Melanosomes are ... Like other immune cells, melanocytes secrete these cytokines in response to activation of Pattern Recognition Receptors (PRRs) ... Millington GW (May 2006). "Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors". ...
Samarpita S, Kim JY, Rasool MK, Kim KS (January 2020). "Investigation of toll-like receptor (TLR) 4 inhibitor TAK-242 as a new ... Resatorvid (TAK-242) is a drug which acts as a selective antagonist of the receptor TLR4. It has antiinflammatory and ... a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions ... M62812 TLR4-IN-C34 Matsunaga N, Tsuchimori N, Matsumoto T, Ii M (January 2011). "TAK-242 (resatorvid), ...
The second hit is characterized by an activation of the Toll-like receptor 4 (TLR4) and CD14, receptors on the Kupffer cell ... identified a receptor present in Kupffer cells, the complement receptor of the immunoglobulin family (CRIg). Mice without CRIg ... The SR-AI/II scavenger receptor is found inside Kupffer cells. This receptor is involved in recognising and binding the lipid A ... March 2006). "CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens". Cell. 124 (5): 915-27 ...
G protein also alters host immune response by inhibiting signaling from several toll-like receptors, including TLR4. Surface ... the RSV F protein also binds to and activates toll-like receptor 4 (TLR4), initiating the innate immune response and signal ... G protein also contains a CX3C fractalkine-like motif that binds to the CX3C chemokine receptor 1 (CX3CR1) on the surface of ... In infants and in people with weakened immune systems, however, the virus may continue to spread for up to 4 weeks (even after ...
... homeostasis and protection as well as in mediation of inflammation via repression of the downstream Toll-like receptor (TLR)-4- ... A study based on sodium butyrate effects on cancer cells conveys that it has an effect on androgen receptor co-regulator ... 4 (7): 801-4. doi:10.1093/protein/4.7.801. PMID 1798702. Maxam AM, Gilbert W (1980). Sequencing end-labeled DNA with base- ... 4 (7): 1083-90. doi:10.1111/j.1365-2958.1990.tb00682.x. PMID 1700257. S2CID 43220370. Willsky GR, Bennett RL, Malamy MH ( ...
Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (PubMed: ... This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory ... LYN kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Interacts with TICAM1 in response to LPS in ... Interacts with MAP3K21; this interaction leads to negative regulation of TLR4 signaling (PubMed:21602844). Interacts with CD36 ...
Toll IL-1 receptor. TLR. Toll-like receptor. Tlr4. murine Toll-like receptor 4. UTR. untranslated region. ... Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 (Tlr4) Salman T. Qureshi, Line Larivière, Gary Leveque, Sophie ... 1998) A family of human receptors structurally related to DrosophilaToll. Proc Natl Acad Sci USA 95:588-593, pmid:9435236.. ... 1998) Toll-like receptor-2 mediates lipopolysaccharide-induced cell signalling. Nature 395:284-288, pmid:9751057.. ...
First in Human Study of an Anti-Toll-like Receptor 4 (TLR4) Monoclonal Antibody (NI-0101) in Adult Healthy Volunteers (NI-0101- ...
Single nucleotide polymorphisms (SNP) of toll-like and NOD-like receptors have been associated with altered receptor activity ... Single nucleotide polymorphism of toll-like receptor 4 (TLR4) is associated with juvenile spondyloarthritis in Croatian ... The399Ile polymorphism of TLR4 may be responsible for altered immune response to microbial infection in variant carriers and ... Statistically significant difference in genotype frequency for Thr399Ile SNP of TLR4 was observed in the jSpA (χ2 = 6.705, p = ...
We investigate the role of toll-like receptor (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)- ... We investigate the role of toll-like receptor (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)- ... Deletion or pharmacological blockade of toll-like receptor 4 (TLR4) confers protection against cyclophosphamide-induced mouse ... Males C57BL/6 (wild-type, WT) and/or TLR4 knockout (TLR4-/-) were treated with an injection of CYP (300 mg/kg, 24 h) or saline ...
Induction of In Vitro Reprogramming by Toll-Like Receptor (TLR)2 and TLR4 Agonists in Murine Macrophages: Effects of TLR " ... Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nat Immunol. 2005;6:571-578. [ ... Synthesis and Toll-Like Receptor 4 (TLR4) Activity of Phosphatidylinositol Dimannoside Analogues. Gary D. Ainge,a,b William ... Different Toll-like receptor agonists induce distinct macrophage responses. J Leukoc Biol. 2001;69:1036-1044. [PubMed] ...
The toll-like receptors (TLRs), including TLR4, have been shown to play a crucial role in vascular inflammatory diseases, such ... A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non-hematopoietic toll like receptor 4 signalling and ... Experimental aneurysms; Toll like receptor 4; Toll like receptor 4 antagonist IAXO-102; Vascular inflammation ... modulation of TLR4-induced mitogen activated protein kinases (MAPK) and p65 NF-kB phosphorylation and expression of TLR4 ...
Developing polymer-drug complex based toll-like receptor (TLR-2/TLR-4) antagonist for modulating gut innate immune system to ... Developing polymer-drug complex based toll-like receptor (TLR-2/TLR-4) antagonist for modulating gut innate immune system to ... Developing polymer-drug complex based toll-like receptor (TLR-2/TLR-4) antagonist for modulating gut innate immune system to ... Developing polymer-drug complex based toll-like receptor (TLR-2/TLR-4) antagonist for modulating gut innate immune system to ...
Prior to LPS-stimulation, the LPS-receptor cluster-of-differentiation 14 (CD14) and Toll-like receptor 4 (TLR4; essential for ... Microglial Heparan Sulfate Proteoglycans Facilitate the Cluster-of-Differentiation 14 (CD14)/Toll-like Receptor 4 (TLR4)- ... The astrocyte TNFα-induction was thus attributed to CD14-independent TLR4 activation and was unaffected by the cells HS status ... Equally, the suppressed LPS-response in Hpa-tg microglia indicated a loss of CD14-dependent TLR4 activation, suggesting that ...
TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the ... 3 Abbreviations used in this paper: TLR, Toll-like receptor; TLR4−/− mice, TLR4-deficient mice; neo, neomycin resistance gene; ... In the present study, we have generated TLR4-deficient (TLR4−/−) mice and examined the LPS responsiveness. TLR4−/− mice showed ... The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 ( ...
TLR4)/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Kappa B (NF-κB) Signaling Pathway in an Adjuvant Arthritis Rat Model - ... Modulates Proinflammatory Cytokines via Regulating the Toll-Like Receptor 4 ( ...
The Zi Qi decoction also suppressed activation of the Toll-like receptor 4 (TLR4)-related NF-kappaB signaling pathway and ... Moreover, another TLR4 downstream pathway, mitogen-activated protein kinase (MAPK), was simultaneously restrained. The results ... CONCLUSIONS:The Zi Qi decoction inhibited liver fibrosis by inhibiting the TLR4-related NF-kB and MAPK signaling pathways and ... Zi Qi Decoction Alleviates Liver Fibrosis by Inhibiting the Toll-Like Receptor 4 (TLR4)-Related Nuclear Factor kappa b (NF-κB) ...
... ... BACKGROUND: Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their ... BACKGROUND: Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their ... article{c1d0477d-e10e-492e-bbfc-c9c22d6e8bae, abstract = {BACKGROUND: Polymorphisms affecting Toll-like receptor (TLR) ...
Toll-like Receptor Cascades (Homo sapiens) * Toll Like Receptor 4 (TLR4) Cascade (Homo sapiens) ... Toll-like Receptor 4 is a microbe associated molecular pattern receptor well known for its sensitivity to bacterial ... One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/interleukin-1-receptor (TIR)-domain-containing adapter ... Differential induction of the toll-like receptor 4-MyD88-dependent and -independent signaling pathways by endotoxins Zughaier, ...
TLR4; 19.0 kilobases, kb) and mice (Tlr4; 91.7 kb), as well as the coding region and splice junctions of Tlr4 from 35 mouse ( ... It has been shown in mice that resistance to LPS is caused by defects in the Toll-like receptor 4 gene (Tlr4), the product of ... We have sequenced the Toll-like receptor 4 gene of humans ( ... The cytoplasmic domain of the Tlr4 protein is highly variable ... No other discernible genes or regions of interspecies conservation lies close to Tlr4 and, in both humans and mice, flanking ...
TLR4)-mediated interleukin-6 (IL-6) production in chemotherapy-induced mucositis, Cancer Chemotherapy and Pharmacology" on ... This review highlights aims to provide a narrative for the involvement of Toll-like receptor (TLR4) in the development of ... This review highlights aims to provide a narrative for the involvement of Toll-like receptor (TLR4) in the development of ... TLR4)-mediated interleukin-6 (IL-6) production in chemotherapy-induced mucositis. Role of toll-like receptor 4 (TLR4)-mediated ...
The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid ... The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid ... The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid ... The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid ...
TAK-242 (Resatorvid), a Small Molecule Inhibitor of Toll-Like Receptor (TLR) 4 Signaling, Binds Selectively to TLR4 and ... TAK-242 (resatorvid), a small molecule specific inhibitor of Toll-like receptor (TLR) 4 signaling, inhibits the production of ... TAK-242 (Resatorvid), a Small Molecule Inhibitor of Toll-Like Receptor (TLR) 4 Signaling, Binds Selectively to TLR4 and ... TAK-242 (Resatorvid), a Small Molecule Inhibitor of Toll-Like Receptor (TLR) 4 Signaling, Binds Selectively to TLR4 and ...
... including components of the toll-like receptor (TLR) system, may drive disease progression. For example, toll-like receptor 4 ( ... with TLR4 and HMGB1 expressed by activated microglia and astrocytes. hSOD1G93A mice lacking TLR4 showed transient improvements ... TLR4 and one of its major endogenous ligands, high-mobility group box 1 (HMGB1), were increased during disease progression in ... This study therefore aimed to extend from these findings and determine the expression and function of TLR4 signalling in ...
A Proof-of-Concept Clinical Trial of Intratumoral Injection of Glucopyranosyl Lipid A (GLA), a Toll-like Receptor 4 (TLR4) ... A Proof-of-Concept Clinical Trial of Intratumoral Injection of Glucopyranosyl Lipid A (GLA), a Toll-like Receptor 4 (TLR4) ...
Identification and analysis of toll like receptor 4 (TLR4) level changes in vascular dementia patients related type 2 diabetes ... we study the molecular mechanism of Toll Like Receptor 4 (TLR4) in autoimmunity respond on VD patients. ... TLR4 protein were at higher presence in VD groups than the normal T2DM group and control group, which consistent with the ... Flow cytometry is used to verify the higher level of TLR4 play an important role in the autoimmune response of VD patients. ...
... we evaluated the effect of these liposomes on Toll-like receptor (TLR) signaling, cytokine production, proinflammatory gene ... Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK ... Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could ... they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling ...
Hennessy EJ, Sheedy FJ, Santamaria D, Barbacid M, ONeill LA., Toll-like receptor 4 (TLR4) down-regulates microRNA-107 ... Oncology, Genetics, Cellular immune response, Toll-like receptors (TLR) Subject (TCD): Cancer , Genes & Society , Immunology, ... Toll-like receptor 4 (TLR4) down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6. ... Toll-like receptors (TLRs) modulate the expression of multiple microRNAs (miRNAs). Here we report the down-regulation of miR- ...
Alias: TLR4/CD284/ARMD10/CD284 antigen/Lps/hTollhomolog of Drosophila toll/TOLL/toll-like receptor 4 ... Mouse TLR4(Toll Like Receptor 4) ELISA Kit. Mouse TLR4(Toll Like Receptor 4) ELISA Kit. To Order: Contact us. Mouse Toll Like ... Mouse TLR7(Toll Like Receptor 7) ELISA Kit. Menu Toggle. *Mouse TPPP(Tubulin Polymerization Promoting Protein) ELISA Kit. Menu ... Mouse TLR4(Toll Like Receptor 4) ELISA Kit. Menu Toggle. * ... Mouse TLR4(Toll-like receptor 4) ELISA Kit. EM0451 FN Test 96T ...
TLR4) Signalling. , TOLLerant - Toll-Like Receptor 4 activation and function in diseases: an integrated chemical-biology ... The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 ( ... The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 (TLR4) Signalling. Int J Mol Sci. 2017 Nov 3;18( ... The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 (TLR4) Signalling.. Int J Mol Sci. 2017 Nov 3;18 ...
Effects of Vitamin D and Calcium Supplementation on Toll-Like Receptor 4 (TLR4) Expression in the Stroma of Normal-Appearing ... Inflammation and the Toll-like Receptor 4 Pathway in Colorectal Carcinogenesis. 2 ... Effects of Vitamin D and Calcium Supplementation on Toll-Like Receptor 4 (TLR4) Expression in the Stroma of Normal-Appearing ... TLR4 signaling pathway has been shown to contribute to the inflammatory processes in the colon. Therefore, understanding how ...
... via Toll-like receptors (TLRs); however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of ... Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs via TLR4 and ... indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants ... the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4- ...
Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of ... To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated ... We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with ... The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure ...
Methods- Cardiac hypertrophy was induced with administration of isoproterenol (5mg/kg/day, sc). TLR4 receptor inhibitor RS-LPS ... As a key regulator of inflammation, toll like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. ... Methods- Cardiac hypertrophy was induced with administration of isoproterenol (5mg/kg/day, sc). TLR4 receptor inhibitor RS-LPS ... There was a marked increase in the TLR4 expression and oxidative stress along with mitochondrial dysfunction in ISO group. TLR4 ...
Mice were euthanized after 4 h of LPS challenge. Signs of sickness and body weights were regularly monitored. At the time of ... Lung and general health effects of Toll-like receptor-4 (TLR4)-interacting SPA4 peptide. *Shanjana Awasthi. ORCID: orcid.org/ ... Toll-like receptor 4 (TLR4) is a transmembrane receptor expressed on immune and non-immune cells in all major organs and ... Awasthi, S., Rahman, N., Rui, B. et al. Lung and general health effects of Toll-like receptor-4 (TLR4)-interacting SPA4 peptide ...
  • Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14 , LY96 and TLR4 (PubMed:11274165). (rcsb.org)
  • upon lipopolysaccharide stimulation, forms a complex including TLR4 and the phosphorylated form of SYK and CEACAM1 , which in turn, recruits PTPN6 that dephosphorylates SYK , reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (By similarity). (rcsb.org)
  • METHODS: Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein B8 (HSPB8). (jrheum.org)
  • TAK-242 (resatorvid), a small molecule specific inhibitor of Toll-like receptor (TLR) 4 signaling, inhibits the production of lipopolysaccharide-induced inflammatory mediators by binding to the intracellular domain of TLR4. (aspetjournals.org)
  • The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 (TLR4) Signalling. (tollerant.eu)
  • To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). (preprints.org)
  • The stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) induces the release of proinflammatory cytokines that activate immune responses. (jax.org)
  • In the current study, direct activation of spinal Toll-like 4 receptors (TLR4) by the intrathecal (IT) administration of KDO2 lipid A (KLA), the active component of lipopolysaccharide, elicits a robust tactile allodynia that is unresponsive to cyclooxygenase inhibition, despite elevated expression of cyclooxygenase metabolites in the spinal cord. (nih.gov)
  • TLR4 is a receptor for lipopolysaccharide (LPS). (biosave.com)
  • Toll-like receptor-4 (TLR4) is a powerful pathway best known for inducing inflammation in response to bacteria-produced lipopolysaccharide. (intechopen.com)
  • We used lipopolysaccharide (LPS), a specific ligand of TLR4, to induce AKI. (lsu.edu)
  • We observed that ATF4 is activated and translocates to the nucleus following lipopolysaccharide (LPS) stimulation via the TLR4-MyD88-dependent pathway. (biomedsearch.com)
  • This receptor has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. (senescence.info)
  • Although TLR4 is essential for the signalling of lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, the response to LPS requires several additional molecules. (ebi.ac.uk)
  • Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase. (ebi.ac.uk)
  • e.g. lipopolysaccharide (LPS) of gram-negative bacteria are recognized by TLR4 while TLR5 recognizes the bacterial protein flagellin. (antikoerper-online.de)
  • Incubation of explants with a neutralizing anti-toll-like receptor-4 monoclonal antibody was used to determine if lipopolysaccharide stimulation of tumor necrosis factor or interleukin-6 secretion was dependent on Toll-like receptor-4 activity. (elsevier.com)
  • Toll-like receptor-4 antibodies significantly inhibited lipopolysaccharide-stimulated tumor necrosis factor secretion by the ciliary body. (elsevier.com)
  • In the present mini-review, several natural and synthetic molecules that modulate the TLR4-mediated LPS (lipopolysaccharide) signalling in animals and humans are considered, and their mechanisms of action are discussed. (biochemsoctrans.org)
  • A popular concept is that a single pathogenic stimulus, such as bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4), is sufficient to induce a reactive proinflammatory phenotype in microglia that exerts neurotoxicity. (pnas.org)
  • We show that chronic activation with either bacterial lipopolysaccharide through Toll-like receptor 4 (TLR4) or leukocyte cytokine IFN-γ induces reactive phenotypes in microglia associated with morphological changes, population expansion, CD11b and CD68 up-regulation, and proinflammatory cytokine (IL-1β, TNF-α, IL-6) and nitric oxide (NO) release. (pnas.org)
  • The complex formed between Toll receptor TLR4 and myeloid differentiation factor MD2 defines a major cell surface receptor for lipopolysaccharide (LPS), a gram-negative bacterial antigen that has been implicated in infectious complications after CRC resection. (aacrjournals.org)
  • Because of its similarity to the lipopolysaccharide lipid A, eritoran acts as TLR4 antagonist and so blocks the excessive reaction triggered by this receptor. (wikipedia.org)
  • Eritoran, because of its structural similarity to the gram-negative bacterial lipopolysaccharide (lipid A) acts as TLR4 antagonist. (wikipedia.org)
  • We report that TLR4 activation by lipopolysaccharide repressed white adipocyte browning in response to β3-adrenergic receptor activation and caused ROS production and mitochondrial dysfunction, while genetic deletion of TLR4 protected mitochondrial function and thermogenesis. (springer.com)
  • The toll-like receptors (TLRs), including TLR4, have been shown to play a crucial role in vascular inflammatory diseases, such as atherosclerosis and aneurysm. (nih.gov)
  • Among ten different human TLRs, TAK-242 selectively bound to TLR4. (aspetjournals.org)
  • Toll-like receptors (TLRs) modulate the expression of multiple microRNAs (miRNAs). (tcd.ie)
  • This sterile inflammation in heart is mainly regulated by toll-like receptors (TLRs). (frontiersin.org)
  • Toll-like receptors (TLRs) are sentinels of the host defense system, which recognize a large number of microbial pathogens. (biomedsearch.com)
  • Binding of microbial ligands to the respective TLRs triggers the release of pro-inflammatory cytokines via the TLR/ IL-1 receptor (TIR) domain and may contribute to the host response, including pro-inflammatory cytokine induction and malarial fever . (bvsalud.org)
  • Toll-like receptors (TLRs) primarily known for the pathogen recognition and subsequent immune responses are being investigated for their pathogenic role in various chronic diseases. (researchwithrutgers.com)
  • OBJECTIVE: Toll-like receptors (TLRs) may activate innate and adaptive immune responses in rheumatoid arthritis (RA) through recognition of microbial as well as endogenous ligands that have repeatedly been found in arthritic joints. (ru.nl)
  • Unlike some TLRs TLR4-mediated adjuvant results on T cell priming happen indirectly through activation of antigen-presenting cells (APC) [16]. (rectalcancersite.com)
  • The body's innate immune response is non-specific and provides the first line of defense against invading pathogens such as bacteria through various receptors that detect bacterial components such as the Toll-like Receptors (TLRs). (bartleby.com)
  • Toll-like receptors (TLRs) play an important role in the innate immune system. (wikipedia.org)
  • Three transcription units were identified within the candidate interval, including Toll-like receptor 4 ( Tlr4 ), part of a protein family with members that have been implicated in LPS-induced cell signaling. (rupress.org)
  • Western blotting, antibody array and ELISA approaches were used to explore the effect of IAXO-102 on TLR4 functional activity on two levels: modulation of TLR4-induced mitogen activated protein kinases (MAPK) and p65 NF-kB phosphorylation and expression of TLR4 dependent proinflammatory proteins. (nih.gov)
  • In adult Drosophila , the toll protein participates in host defense against fungal infection ( 1 ). (jimmunol.org)
  • One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/interleukin-1-receptor (TIR)-domain-containing adapter protein) and MyD88, which leads to the NFkB activation and the induction of pro-inflammatory cytokines. (reactome.org)
  • Interstrain analyses reveal that Tlr4 is a polymorphic protein and that the extracellular domain is far more variable than the cytoplasmic domain, both among strains and among species. (biomedcentral.com)
  • The cytoplasmic domain of the Tlr4 protein is highly variable at the carboxy-terminal end. (biomedcentral.com)
  • Subsequently, overexpression of the wild-type Tlr4 protein was found to enhance LPS signal transduction in wild-type macrophages, lowering the effective concentration (EC 50 ) for LPS by a factor of 30, whereas overexpression of the Tlr4 Lps-d isoform represented in C3H/HeJ mice almost completely suppresses signaling [ 12 ]. (biomedcentral.com)
  • The present study demonstrated, using coimmunoprecipitation, that TAK-242 interferes with protein-protein interactions between TLR4 and its adaptor molecules. (aspetjournals.org)
  • TAK-242 inhibited the association of TLR4 with TIR domain-containing adaptor protein (TIRAP) or TRIF-related adaptor molecule (TRAM) in HEK293 cells overexpressing TLR4, MD-2 and TIRAP or TRAM, respectively. (aspetjournals.org)
  • After collecting the patients' Cerebrospinal Fluid (CSF), it tests the level of TLR4 in CSF and blood at gene and protein degrees, respectively. (alliedacademies.org)
  • TLR4 protein were at higher presence in VD groups than the normal T2DM group and control group, which consistent with the results of TLR4 mRNA expression in CSF. (alliedacademies.org)
  • In addition, the reduced fibrosis was found to be associated with the decreased protein expression of high-mobility group box 1 (HMGB1) as well as toll like receptor (TLR) 4. (frontiersin.org)
  • The Tlr4 , toll-like receptor 4, gene encodes a protein that has a critical role in pathogen recognition and activation of the innate immune system. (jax.org)
  • TLR4 (Toll-like receptor 4) is a mammalain homolog of the Drosophila toll protein. (biosave.com)
  • The human TLR4 is a type-1 transmembrane protein containing 799aa residues. (biosave.com)
  • Human Toll-like receptor-4 (TLR4) was discovered in 1997 through a bioinformatics approach based on the homology of similar Toll protein found in Drosophila [ 1 , 2 ]. (intechopen.com)
  • Drosophila Toll protein-mediated protection against fungus infection was the first clue suggesting the role of mammalian TLR4 in activation of the immune system. (intechopen.com)
  • Based on exquisite sensitivity to LPS and high level of TLR4 expression in macrophages, it was initially thought that the main function of this protein is restricted to an inflammatory response aimed at eradication of microbial pathogens. (intechopen.com)
  • TLR4/MD2 expressing CHO cells/chimeric TLR4/MD2 fusion protein. (abcam.com)
  • The TLR4 cDNA codes for a protein consisting of 799 amino acids with approximate molecular weight of 88 kDa (6). (novusbio.com)
  • The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. (senescence.info)
  • Protein expression levels of TLR4 in the liver of CGA (chlorogenic acid)- and CCl4-treated rats were measured by Western blot using TLR4 antibody 19811-1-AP. (cosmobio.co.jp)
  • This family of type I transmembrane protein is characterized by an extracellular domain with leucine-rich repeats and a cytoplasmic domain with homology to the type I IL-1 receptor. (thermofisher.com)
  • This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. (antikoerper-online.de)
  • This gene encodes a member of the interleukin-1 receptor-associated kinase protein family. (antikoerper-online.de)
  • This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of Toll-like receptor signaling. (antikoerper-online.de)
  • Signaling pathways via TLR4 activate various transcription factors like Nuclear factor kappa-light-chain-enhancer (NF-κB), activator protein 1 (AP1), Signal Transducers and Activators of Transcription family of transcription factors (STAT1) and Interferon regulatory factors (IRF's), which are the key players regulating the inflammatory response. (researchwithrutgers.com)
  • TLR4 receptors are type I transmembrane protein including extracellular leucine wealthy repeats and intracellular TIR sign domains [4] and so are expressed on a number of sponsor immune and nonimmune Ozarelix cells. (rectalcancersite.com)
  • The process of LPS sensing and signal amplification in humans is based on the sequential action of specific receptors situated in the extracellular side of the innate immunity cells, which bind and transfer LPS to TLR4: LBP (LPS-binding protein), CD14, MD-2 (myeloid differentiation protein 2). (biochemsoctrans.org)
  • To further investigate Toll-like receptor signaling in vaccinia infection, we first focused on TRIF, the only known adapter protein for TLR3. (pubmedcentralcanada.ca)
  • LPS-induced TLR4 signaling leads to activation of various downstream Mitogen-Activated Protein Kinases (MAPK) that have been shown to play key roles in cell proliferation, apoptosis, and adhesion ( 15-19 ). (aacrjournals.org)
  • Toll-like receptor (TLR) 2 mediates inflammatory responses to oligomerized RrgA pneumococcal pilus type 1 protein. (semanticscholar.org)
  • The protein expression of TLR4, mitogen‑activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) were also determined by western blot analysis. (spandidos-publications.com)
  • In addition, the protein levels of TLR4, phosphorylated (p‑)extracellular signal‑regulated kinase, p‑c‑Jun N‑terminal kinase and p‑P38 were reduced upon GLN pretreatment. (spandidos-publications.com)
  • TLR4 and its associated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways have been demonstrated to be correlated with LPS-induced inflammation ( 5 , 6 ). (spandidos-publications.com)
  • Defining the molecular basis of interaction between R3 receptor-type protein tyrosine phosphatases and VE-cadherin. (bireme.br)
  • Receptor-type protein tyrosine phosphatases (RPTPs) of the R3 subgroup play key roles in the immune, vascular and nervous systems. (bireme.br)
  • The399Ile polymorphism of TLR4 may be responsible for altered immune response to microbial infection in variant carriers and represent a mechanism of triggering overproduction of proinflammatory cytokines and long-term inflammation in jSpA. (sigmaaldrich.com)
  • We investigate the role of toll-like receptor (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)-induced mouse cystitis. (urotoday.com)
  • Our findings reveal a central role for TLR4 signaling pathway in initiating CYP-induced bladder dysfunction and inflammation, and thus emphasize that TLR4 receptor blockade may have clinical value for IC/BPS treatment. (urotoday.com)
  • Therefore, pharmacological inhibition of TLR-2/TLR-4 has been a new promising strategy for preventing inflammation in IBD and colorectal cancer. (jimmunol.org)
  • In macrophages and dendritic cells, LPS-mediated activation of TLR4 triggers the biosynthesis of diverse mediators of inflammation, such as TNF-alpha and IL6, and activates the production of co-stimulatory molecules required for the adaptive immune response. (reactome.org)
  • Misra S, Hascall VC, Markwald RR et al (2015) Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer. (springer.com)
  • As a key regulator of inflammation, toll-like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. (frontiersin.org)
  • The expression of TLR4 is increased at systemic and tissue levels in many disease conditions, including lung infection and inflammation [ 1 ]. (biomedcentral.com)
  • The Tlr4 Lps-del spontaneous mutation exhibits a defective response to LPS stimulation and affects Toll signaling pathways involved with inflammation, including susceptibility to various bacterial infections, effects of tissue ischemia (including cerebral and retinal ischemia), myocardial infarction, neurodegeneration, and tumor immune responses. (jax.org)
  • We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension. (springer.com)
  • First, we determined the mechanism by which AngiotensinII (AngII)-induced inflammation is modulated by TLR4 using an in vitro model of rat tubulo-epithelial cells. (lsu.edu)
  • In TLR4-silenced cells, the expression of TLR4 was decreased, activation of NF-κB was reduced, inflammation and oxidative stress were attenuated, suggesting a role for TLR4 in potentiating AngII-induced renal inflammation. (lsu.edu)
  • Compared to LPS-administered rats, the BB-pretreated animals exhibited improved renal hemodynamics, attenuated expression of TLR4 and inflammation. (lsu.edu)
  • Two of these receptors, TLR2 and TLR4, are pattern recognition receptors and signaling molecules in response to bacterial lipoproteins and have been implicated in innate immunity and inflammation. (thermofisher.com)
  • Persistent joint inflammation in the latter phase of the model was significantly suppressed in TLR-4(-/-) mice. (ru.nl)
  • Rather, TLR4 recognizes a molecule in or on vaccinia virus to bring about a protective response that may be due to an ability to diminish the degree of inflammation caused by vaccinia infection. (pubmedcentralcanada.ca)
  • CONCLUSIONS: The G allele of the TLR-4 gene, which is associated with a lower inflammation response, was associated with a lower risk of coronary stenosis but not with the occurrence of MI and hence is not a major factor in the development of coronary atherosclerosis. (biomedsearch.com)
  • The Zi Qi decoction inhibited liver fibrosis by inhibiting the TLR4-related NF-kB and MAPK signaling pathways and preventing activation of HSCs. (medscimonit.com)
  • TLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. (reactome.org)
  • Taken together, our study indicated that ICQA could protect against CCl 4 -induced liver fibrosis probably through suppressing the HMGB1/TLR4/NF-κB signaling pathways. (frontiersin.org)
  • Results We found that a shared network of genes/proteins is overrepresented by immune response-related pathways, post-translational modifications of nuclear receptors, and platelet-related processes, including activation and platelet signalling. (medscape.com)
  • We hypothesized that inhibiting Toll-like receptor 4 (TLR4), an upstream modulator of several inflammatory pathways, would prevent the progression of renal diseases. (lsu.edu)
  • Members of this family are essential components of the Toll/IL-R immune signal transduction pathways. (antikoerper-online.de)
  • Here we review the therapeutic targets involved in TLR-4 signaling pathways that are critical for suppressing chronic inflammatory disorders. (researchwithrutgers.com)
  • To further elucidate critical downstream pathways involving TLR4-mediated intestinal tumorigenesis, we examined the effects of exogenously administered PGE 2 in TLR4-/- mice to see if PGE 2 bypasses the protection from colitis-associated tumorigenesis.Method: Mouse colitis-associated neoplasia was induced by azoxymethane (AOM) injection followed by two cycles of dextran sodium sulfate (DSS) treatment. (elsevier.com)
  • Toll-like receptor (TLR) is normally one of most significant pathogen design recognitions (PPRs) which motivate intracellular signaling cascades via the nuclear-factor κB (NF-κB) caspase-dependent and mitogen-activated proteins kinase (MAPK) signaling pathways to tirgger host's immune system responses [12]. (bio-aromatica.com)
  • Like a gram bad bacterium it was likely that toll-like receptor signaling pathways contributed to this unpredicted finding. (web-succes.com)
  • Signalling pathways recruited by TLR4 in response to LPS and mitochondria-derived ligands were found to be the same. (kent.ac.uk)
  • In this study, we show that ATF3 was upregulated via Toll-like receptor (TLR) pathways in response to S. pneumoniae infection in vitro. (semanticscholar.org)
  • Among its related pathways are Activated TLR4 signalling and RET signaling . (genecards.org)
  • The downregulation of TLR4-mediated MAPK and NF-κB signaling pathways inhibits the LPS-induced inflammatory response, and provides a protective effect in various organs against sepsis ( 5 , 6 ). (spandidos-publications.com)
  • Biological testing of these PIM compounds indicated that the agonist activity was TLR4 dependent. (pubmedcentralcanada.ca)
  • MyD88 and TRIF synergistic interaction is required for TH1-cell polarization with a synthetic TLR4 agonist adjuvant. (semanticscholar.org)
  • The mitochondrial perturbations that were observed in hypertrophy heart was normalized after administration of TLR4 inhibitor but not with the agonist. (frontiersin.org)
  • This randomized pilot clinical trial studies melanoma antigen recognized by T-cells 1 (MART-1) antigen with or without toll-like receptor 4 (TLR4) agonist glucopyranosyl lipid A-stable oil-in-water emulsion (GLA-SE) in treating patients with stage II-IV melanoma that has been removed by surgery. (clinicaltrials.gov)
  • Giving TLR4 agonist GLA-SE with MART-1 antigen may help increase the immune response to MART-1a antigen. (clinicaltrials.gov)
  • The newly designed, pH-dependent opioid agonist NFEPP induced analgesia exclusively through peripheral opioid receptors in models of neuropathic and abdominal pain. (lww.com)
  • Particularly the TLR4 agonist monophosphoryl lipid A (MPL? (rectalcancersite.com)
  • C3H/HeJ mice have a point mutation within the coding region of the Tlr4 gene, resulting in a nonconservative substitution of a highly conserved proline by histidine at codon 712, whereas C57BL/ 10ScCr mice exhibit a deletion of Tlr4 . (rupress.org)
  • Identification of distinct mutations involving the same gene at the Lps locus in two different hyporesponsive inbred mouse strains strongly supports the hypothesis that altered Tlr4 function is responsible for endotoxin tolerance. (rupress.org)
  • Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. (jimmunol.org)
  • Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response. (jimmunol.org)
  • The hyporesponsive phenotype of the C3H/HeJ mouse maps to the Lps locus (endotoxin unresponsive gene locus) on mouse chromosome 4 ( 12 ). (jimmunol.org)
  • Recent genetic and physical mapping of the Lps locus identifies TLR4 as a candidate gene in the critical region ( 12 ). (jimmunol.org)
  • We also detected a single point mutation in the TLR4 gene of C3H/HeJ mice. (jimmunol.org)
  • These results demonstrate that TLR4 is the gene product of the Lps locus. (jimmunol.org)
  • The murine TLR4 genomic clone was screened from the 129/SvJ mouse genomic library (Stratagene, La Jolla, CA). A targeting vector was designed to replace a 2.54-kbp genomic fragment with neomycin resistance gene ( neo ) from pMC1-neo-poly(A) (Stratagene). (jimmunol.org)
  • It has been shown in mice that resistance to LPS is caused by defects in the Toll-like receptor 4 gene ( Tlr 4), the product of which is thought to bind LPS and mediate LPS signal transduction in immune system cells. (biomedcentral.com)
  • Here we determine the genetic variation within the human TLR4 gene encoding the principal receptor for bacterial endotoxin recognition in typhoid fever patients. (cdc.gov)
  • TLR4 gene structure and fragment design for dHPLC. (cdc.gov)
  • The phenotype was subsequently identified as a mutation in the Tlr4 gene. (jax.org)
  • Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. (jax.org)
  • 74723bp of genomic DNA sequence have been removed, apparently encompasing only the Tlr4 gene. (jax.org)
  • These floxed mutant mice possess loxP sites flanking exon 3 of the Tlr4 gene. (jax.org)
  • These mice possess loxP sites on either side of exon 3 of the targeted Tlr4 gene. (jax.org)
  • Toll-like receptor 4 (TLR4) gene polymorphisms in giant cell arteritis. (cdc.gov)
  • To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, and clinical features of giant cell arteritis (GCA). (cdc.gov)
  • Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, and clinical expression of, GCA in Italian patients. (cdc.gov)
  • We blocked TLR4 using gene silencing strategy in NRK52E cells. (lsu.edu)
  • Ischemia/reperfusion-induced intestinal injury requires both toll-like receptor 4 (TLR4) signaling through myeloid differentiation main response gene (88) (MyD88) and complement activation. (web-succes.com)
  • The purpose of this study was to investigate the role of a common Asp299Gly polymorphism of the TLR-4 gene in atherosclerosis. (biomedsearch.com)
  • Macrophages and B cells from TLR4-deficient mice did not respond to LPS. (jimmunol.org)
  • Peritoneal macrophages were isolated 3 days after i.p. thioglycolate injection, and then 5 × 10 4 cells were cultured with various reagents for 24 h. (jimmunol.org)
  • TLR4, also known as CD284, has been demonstrated to act as a receptor for LPS on human monocytes and macrophages. (novusbio.com)
  • Here we show, for the first time, that lipid flippases are essential to dampen the inflammatory response and to mediate the endotoxin-induced endocytic retrieval of Toll-like receptor 4 (TLR4) in human macrophages. (gut-research.com)
  • Pre-treatment of THP-1 myeloid macrophages with TLR4-neutralising antibody before exposure to mitochondria extracts or LPS attenuated the inflammatory responses. (kent.ac.uk)
  • Challenge of primary bone marrow macrophages isolated from TLR4 mutant and control mice suggested that TLR4 recognizes a viral ligand rather than an endogenous ligand. (pubmedcentralcanada.ca)
  • Here, we investigated the effect of pattern recognition receptors (PRR) activation in macrophages, especially the toll-like receptor 4 (TLR4) and Nod-like receptor 3 (NLRP3), on white adipocyte browning. (springer.com)
  • These findings suggest that TAK-242 binds selectively to TLR4 and subsequently disrupts the interaction of TLR4 with adaptor molecules, thereby inhibiting TLR4 signal transduction and its downstream signaling events. (aspetjournals.org)
  • Furthermore, signal transduction occurs in a MyD88-dependent fashion as CLI-095, a TLR4 signaling inhibitor that blocks the MyD88-independent pathway, had no significant effect on mRNA expression or PGE2 production. (colorado.edu)
  • TLR4 uses a mechanism similar to that of the IL-1 receptor for signal transduction that leads to activation of NF-kB. (biosave.com)
  • In this report, we found that ATF4 is also involved in the TLR-mediated innate immune response, which participates in TLR4 signal transduction and mediates the secretion of a variety of cytokines. (biomedsearch.com)
  • Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression. (jrheum.org)
  • Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs via TLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs. (nature.com)
  • The effect of TLR4 on tumor progression appears to depend on which cells TLR4 resides and the particular ligand involved. (jax.org)
  • For example, enhanced prostrate tumor progression as a result of TLR4 response to a tumor-derived ligand such as Peroxiredoxin is not seen in the Tlr4 deficient mutant mice (Riddell et al. (jax.org)
  • While these functions in normal cells are essential for host defense and tissue repair, TLR4 overexpression in malignant cells promotes tumor growth and metastasis. (intechopen.com)
  • This is because pro-oncogenic effects of activated TLR4 in tumor cells are amplified by similar event in TLR4-positive tumor-associated cells including endothelial cells and their mobilized progenitors. (intechopen.com)
  • Here, we summarize the current knowledge of the TLR4 pathway and its functional outcomes in normal and tumor cells. (intechopen.com)
  • The review considers several open questions regarding the impact of TLR4-mediated pro- and antitumor effects, structural requirements for recognition of the TLR4 complex, and a potential contribution of chemotherapy to tumor spread. (intechopen.com)
  • In support of this direct modulation, tumor necrosis factor, interleukin-1β, and interleukin-6 rapidly modulate the function of neurotransmitter receptors such as AMPA receptor, NMDA receptor, glycine receptor, and GABAR, which results in enhanced excitatory synaptic transmission and suppressed inhibitory synaptic transmission in the spinal pain circuit. (medscape.com)
  • [ 166 ] Electrophysiologic analysis reveals that tumor necrosis factor increases glutamate release in transient receptor potential ion channel V1 + C-fiber terminals, leading to enhanced excitatory synaptic transmission in lamina IIo excitatory spinal cord dorsal horn interneurons. (medscape.com)
  • [ 203 ] Both type I and type II receptors of tumor necrosis factor are involved in behavioral manifestations of central sensitization after intrathecal tumor necrosis factor treatment or during formalin-induced second-phase pain. (medscape.com)
  • [ 204 ] Notably, caspase-6 triggers tumor necrosis factor release from microglia to elicit central sensitization via tumor necrosis factor receptor signaling. (medscape.com)
  • Reverse transcription-polymerase chain reaction was used to detect mRNAs for toll-like receptor-4, tumor necrosis factor-α, interleukin-1β, interleukin-6 and interleukin-8, 3hr after stimulation of cultured iris microvascular endothelial cells. (elsevier.com)
  • Furthermore, TLR-4(-/-) mice expressed less IL-1beta, tumor necrosis factor alpha, IL-6, and IL-23, cytokines that are implicated in IL-17 production. (ru.nl)
  • The serum levels of tumor necrosis factor α (TNF‑α), interleukin (IL)‑1β and IL‑6 were detected by enzyme‑linked immunosorbent assay, while the mRNA levels of toll‑like receptor (TLR)4, TNF‑α, IL‑1β and IL‑6 were examined by reverse transcription‑quantitative polymerase chain reaction. (spandidos-publications.com)
  • Microglial Heparan Sulfate Proteoglycans Facilitate the Cluster-of-Differentiation 14 (CD14)/Toll-like Receptor 4 (TLR4)-Dependent Inflammatory Response. (sigmaaldrich.com)
  • Isolated primary astroyctes expressed TLR4, but notably lacked CD14 and in contrast to microglia, LPS challenge induced a similar TNFα response in Ctrl and Hpa-tg astrocytes, while neither released IL1β. (sigmaaldrich.com)
  • The astrocyte TNFα-induction was thus attributed to CD14-independent TLR4 activation and was unaffected by the cells HS status. (sigmaaldrich.com)
  • Equally, the suppressed LPS-response in Hpa-tg microglia indicated a loss of CD14-dependent TLR4 activation, suggesting that microglial HSPGs facilitate this process. (sigmaaldrich.com)
  • We conclude that microglial HSPGs facilitate CD14-dependent TLR4 activation and that heparanase can modulate this mechanism. (sigmaaldrich.com)
  • TAK-242 inhibited the TIRAP-mediated activation of nuclear factor kappa B (NF-kB) and the TRAM-mediated activation of NF-kB and interferon-sensitive response element in HEK293 cells stably expressing TLR4, MD-2 and CD14. (aspetjournals.org)
  • Results indicate that TLR4 is indeed activated by (+)-morphine, producing PGE2 and increasing the mRNA of IκB, CD14, and TLR4 at 100 µM (+) morphine 24 h after incubation. (colorado.edu)
  • TLR4 physically associates with another molecule called MD-2, and together with CD14, this complex is responsible for LPS recognition and signaling. (thermofisher.com)
  • We investigated the expression of the functional endotoxin receptor proteins Toll-like receptor-4 and CD14 in human eyes. (elsevier.com)
  • Toll-like receptor-4 and CD14 proteins were detected by immunohistochemical analysis of sections of whole human eyes embedded in paraffin with monoclonal antibodies against human toll-like receptor-4 (HTA-125), human CD14 (RPA-M1), or as a control, an irrelevant mouse IgG1k (MOPC-21). (elsevier.com)
  • By immunohistochemistry, human ciliary body non-pigmented epithelial cells showed strong expression of the endotoxin receptor proteins, toll-like receptor-4 and CD14. (elsevier.com)
  • Our results show that the ciliary body also expresses CD14, which is anatomically colocalized with toll-like receptor-4. (elsevier.com)
  • The juxtaposition of toll-like receptor-4 and CD14 in the anterior uveal tract helps to explain the sensitivity of the iris/ciliary body to bacterial endotoxin as seen in the standard animal model of endotoxin-induced uveitis. (elsevier.com)
  • We classified the compounds active on TLR4 pathway depending on the specific molecular targets (LPS, LBP, CD14, MD-2 or TLR4). (biochemsoctrans.org)
  • Small molecules developed by our group are described that inhibit LPS-stimulated TLR4 activation by selectively targeting the LPS-CD14 interaction. (biochemsoctrans.org)
  • NI-0101 is an anti-Toll-like receptor monoclonal antibody. (clinicaltrials.gov)
  • There are currently no images for TLR4 Antibody (NB100-56727APC). (novusbio.com)
  • This antibody was developed by immunizing mice with Ba/F3 cell line expressing human TLR4 cell surface antigen. (novusbio.com)
  • Flow Cytometry: TLR4 Antibody (HTA125) [PE] [NB100-56062] - Intracellular flow analysis of TLR4 in human PBMCs using NB100-56062 at 0.5 ug/10^6 cells. (novusbio.com)
  • Flow Cytometry: TLR4 Antibody (HTA125) [PE] [NB100-56062] - Cell surface analysis of TLR4 on ThP1 cells using TLR4 antibody at 2 ug/10^6 cells. (novusbio.com)
  • The following antibody was used in this experiment: CD284 (TLR4) Monoclonal Antibody (UT41), Alexa Fluor 488, eBioscience™ from Thermo Fisher Scientific, catalog # 53-9041-82, RRID AB_469944. (thermofisher.com)
  • Description: The UT41 monoclonal antibody was generated against BaF3 cells overexpressing mouse TLR4. (thermofisher.com)
  • The MTS510 monoclonal antibody co-immunoprecipitates MD-2 (~30 kDa) and TLR4 (~100 kDa), and preferentially reacts with TLR4 that is associated with MD-2. (thermofisher.com)
  • In comparison, binding of the UT41 monoclonal antibody occurs with and without formation of the TLR4/MD-2 complex. (thermofisher.com)
  • The pharmacological blockade of the TLR4 by resatorvid (10 mg/kg) was also performed 1 h prior CYP-injection in WT mice. (urotoday.com)
  • These functional and molecular alterations induced by CYP were prevented in TLR4-/- and resatorvid-treated mice. (urotoday.com)
  • To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. (jimmunol.org)
  • Furthermore, C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family. (jimmunol.org)
  • Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-κB. (jimmunol.org)
  • In the present study, we have generated TLR4-deficient (TLR4 −/− ) mice and examined the LPS responsiveness. (jimmunol.org)
  • TLR4 −/− mice showed hyporesponsive to LPS to an extent similar to that of C3H/HeJ mice. (jimmunol.org)
  • No other discernible genes or regions of interspecies conservation lies close to Tlr4 and, in both humans and mice, flanking sequences and introns are rich in repeats of retroviral origin. (biomedcentral.com)
  • This parallels recent preclinical findings showing that TLR4 knockout mice, which are protected from developing severe GI mucositis, completely lack an IL-6 response. (deepdyve.com)
  • This study therefore aimed to extend from these findings and determine the expression and function of TLR4 signalling in hSOD1 G93A mice, the most widely established preclinical model of ALS. (biomedcentral.com)
  • TLR4 and one of its major endogenous ligands, high-mobility group box 1 (HMGB1), were increased during disease progression in hSOD1 G93A mice, with TLR4 and HMGB1 expressed by activated microglia and astrocytes. (biomedcentral.com)
  • hSOD1 G93A mice lacking TLR4 showed transient improvements in hind-limb grip strength and significantly extended survival when compared to TLR4-sufficient hSOD1 G93A mice. (biomedcentral.com)
  • These results suggest that enhanced glial TLR4 signalling during disease progression contributes to end-stage ALS pathology in hSOD1 G93A mice. (biomedcentral.com)
  • In the present study, we addressed this by examining the expression of HMGB1 and TLR4 during defined stages in hSOD1 G93A mice. (biomedcentral.com)
  • In order to identify the contribution of TLR4 signalling in hSOD1 G93A pathogenesis, we generated hSOD1 G93A mice lacking TLR4 and compared them to hSOD1 G93A mice in respect to survival and muscle strength. (biomedcentral.com)
  • Mice were euthanized after 4 h of LPS challenge. (biomedcentral.com)
  • The functionally similar Tlr4 Lps-d mutation found in C3H/HeJ mice (# 000659 ) is a point mutation that causes an amino acid substitution. (jax.org)
  • Tlr4 -deficient mice display significantly reduced expression of proinflammatory genes compared to controls 24 h after reperfusion triggered by retinal ischemic injury. (jax.org)
  • In mice that are genetically tolerant to endotoxin, mutations have been identified in the intracellular domain of TLR4 that abolish LPS responsiveness. (biosave.com)
  • Background: We have previously found that TLR4-deficient (TLR4-/-) mice demonstrate decreased expression of mucosal PGE 2 and are protected against colitis-associated neoplasia. (elsevier.com)
  • Mucosal Cox-2 and amphiregulin (AR) expression, prostanoid synthesis, and EGFR activation were analyzed.Results: In control mice treated with PBS, the average number of tumors was greater in WT mice (n = 13) than in TLR4-/- mice (n = 7). (elsevier.com)
  • 28.6% of PBS-treated TLR4-/- mice developed dysplasia (tumors/animal: 0.4 ± 0.2). (elsevier.com)
  • 0.05) of the high dose group and 33.3% (tumors/animal: 0.3 ± 0.5) of the low dose group developed dysplasia in TLR4-/- mice. (elsevier.com)
  • METHODS: Chronic SCW arthritis was induced by 4 repeated intraarticular injections of SCW fragments in wild-type, TLR-2(-/-), and TLR-4(-/-) mice. (ru.nl)
  • In the chronic phase, TLR-4 actively contributed to matrix metalloproteinase (MMP)-mediated cartilage destruction and to osteoclast formation, since the expression of the MMP-specific aggrecan neoepitope VDIPEN and the osteoclast marker cathepsin K was significantly reduced in TLR-4(-/-) mice. (ru.nl)
  • Accordingly, SCW-specific IL-17 production was found to be dependent on TLR-4 activation, since T cells from arthritic TLR-4(-/-) mice produced markedly less IL-17 upon SCW stimulation, whereas interferon-gamma production remained unaffected. (ru.nl)
  • The impairment of T cell adjuvant results and faulty DC maturation in TRIF lps/lps mice after TLR4 excitement was due mainly to lack of type I IFN creation indicating that type I interferons are central to TLR4's adjuvant results. (rectalcancersite.com)
  • Following respiratory infection with vaccinia, mice lacking TLR4 signaling had greater viral replication, hypothermia, and mortality than control animals. (pubmedcentralcanada.ca)
  • Mice with a nonfunctional mutant version of TLR4 are more susceptible to vaccinia infection than wild-type controls. (pubmedcentralcanada.ca)
  • In support of this hypothesis, we report here that LPS enhances liver metastasis of human CRC cells that express TLR4/MD2 after intrasplenic graft of immunocompromised nude mice. (aacrjournals.org)
  • Our data show that increased TLR4 ligand pool in cardiac hypertrophy may exaggerate the disease progression. (frontiersin.org)
  • Then, in this study, we analyze the role of NLRP3, PICs, chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), and neurohormone level in the development of prehypertension. (springer.com)
  • An in vitro ELISA-based TLR4-ligand binding assay, in which the ligand-binding domain of human TLR4 was immobilised, showed that mitochondria extracts contain endogenous TLR4 ligands. (kent.ac.uk)
  • The extracellular domain has leucine-rich repeats and the intracellular domain is similar to that of IL-1 receptor. (biosave.com)
  • However, the role of intracellular NOD like receptors, such as pyrin domain containing 3 (NLRP3) in hypertension remains unknown. (springer.com)
  • LPS has been shown to bind directly to the TLR4/MD2 receptor complex ( 13, 14 ) that initiates the intracellular signaling cascade in a MyD88-dependant or MyD88-independent manner ( 15 ). (aacrjournals.org)
  • The activation of endogenous interleukin-1 receptor-associated kinase in RAW264.7 cells was also inhibited by TAK-242 treatment. (aspetjournals.org)
  • We failed to detect any polymorphisms within the TLR-9/ interleukin-1 receptor domain. (bvsalud.org)
  • A novel small molecule TLR4 antagonist (IAXO-102) negatively regulates non-hematopoietic toll like receptor 4 signalling and inhibits aortic aneury. (nih.gov)
  • The main goal of this study was to determine the potential of IAXO-102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental abdominal aortic aneurysm (AAA) development. (nih.gov)
  • These results demonstrate the ability of IAXO-102 to negatively regulate TLR4 signalling and to inhibit experimental AAA development, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of AAA. (nih.gov)
  • In the current study, we have developed a novel polymer-drug complex (Ora-Curcumin) as a TLR-2/TLR-4 antagonist to modulate the gut innate immune system. (jimmunol.org)
  • In addition, Ora-Curcumin was potent TLR-4 antagonist that significantly inhibited the release of IL-8 and TNF-a from TLR-4 expressing human kidney epithelial cells (HEK293TLR4 YFP -MD2) and mouse dendritic cells, respectively, in response to TLR stimulation with Monophosphoryl Lipid A (MPLA) or dead E. coli . (jimmunol.org)
  • To this end, we have developed a unique polymer based water soluble TLR-2/TLR-4 antagonist which also provides enhanced local delivery to colon to prevent or treat IBD and colorectal cancer. (jimmunol.org)
  • ARM I: Patients receive MART-1 antigen and TLR4 antagonist GLA-SE intramuscularly (IM) on day 1. (clinicaltrials.gov)
  • We showed that enhanced adherence elicited by LPS in these cells could be blocked at three different levels, using Eritoran (TLR4 small molecule antagonist), PI-103 (PI3K inhibitor), or anti-β1 integrin blocking antibodies. (aacrjournals.org)
  • Moreover, endotoxin-induced internalization of TLR4 was strongly reduced and coincided with impaired endosomal MyD88-independent signaling. (gut-research.com)
  • We conclude that lipid flippases are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4. (gut-research.com)
  • Toll-like receptor-4 mRNA was constitutively expressed in iris endothelial cells and slightly down-regulated by endotoxin. (elsevier.com)
  • The identification of the bacterial endotoxin receptors for innate immunity, most notably TLR4 (Toll-like receptor 4), has sparked great interest in therapeutic manipulation of the innate immune system. (biochemsoctrans.org)
  • Targeting of a receptor or molecule related to disease pathology with a synthetic small molecule or peptide, is an attractive therapeutic approach. (biomedcentral.com)
  • TLR4 signalling of LPS stimulation requires the presence of the MD-2 molecule. (novusbio.com)
  • Lastly, PGE 2 treatment increased mucosal expression of AR and Cox-2, thus inducing EGFR activation and forming a positive feedback mechanism to amplify mucosal Cox-2.Conclusions: These results highlight the importance of PGE 2 as a central downstream molecule involving TLR4-mediated intestinal tumorigenesis. (elsevier.com)
  • The transmembrane and the cytoplasmic domain of murine TLR4 (amino acid residue 623 to 835) were fused to the extracellular domain of murine CD4 (amino acid residue 1 to 384). (jimmunol.org)
  • Toll-like receptor 4 (TLR4) is a transmembrane receptor expressed on immune and non-immune cells in all major organs and tissues. (biomedcentral.com)
  • The Toll-like receptor (TLR) family in mammal comprises a family of transmembrane proteins characterized by multiple copies of leucine rich repeats in the extracellular domain and IL-1 receptor motif in the cytoplasmic domain. (novusbio.com)
  • Toll-like receptors are a class of transmembrane proteins that detect the presence of infectious organisms and activate host innate and adaptive immune responses. (pubmedcentralcanada.ca)
  • METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the TLR4 promoter (4,3 kb) in Swedish blood donors. (lu.se)
  • Our findings demonstrate that lack of TLR4 signalling has a protective effect on hSOD1 G93A pathology, significantly extending survival and transiently improving motor function. (biomedcentral.com)
  • These findings suggest that HA fragments interact with TLR4 and educate macrophage polarization to an M2-like phenotype via miR-935. (springer.com)
  • Taken together, these findings suggest that spinal TLR4-mediated hyperpathic states are mediated at least in part through activation of microglial 15-LOX-1. (nih.gov)
  • These findings suggest TLR4-mediated responses to malaria in vivo and TLR-4 polymorphisms to be associated with disease manifestation. (bvsalud.org)
  • From these findings, we made the conclusion that ghrelin could attenuate the symptoms of diabetic encephalopathy, which alleviates inflammatory reaction of diabetic encephalopathy by regulating TLR4/NF-κB pathway. (springer.com)
  • We report our findings that TLR4 has a protective effect in vaccinia infection. (pubmedcentralcanada.ca)
  • Our findings suggest that inhibiting LPS-induced TLR4 signaling could improve therapeutic outcomes by preventing cancer metastasis during the perioperative period of CRC resection. (aacrjournals.org)
  • This event induces the formation of a heterodimer of TLR4 and TLR6 , which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1 , CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. (rcsb.org)
  • Sustaining inflammatory response is one of the molecular mechanisms of diabetic encephalopathy and TLR4 signaling has close relationship with inflammatory response. (springer.com)
  • Collectively, we demonstrated that inflammatory response to obesity, such as TLR4 and NLRP3 inflammasome activation as well as IL-1β secretion, attenuates β3-adrenoreceptor-induced beige adipocyte formation via oxidative stress and mitochondrial dysfunction. (springer.com)
  • Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [MIM:611488]. (abcam.com)
  • Carbachol-induced bladder contractions were significantly reduced in the CYP group, which was paralleled by reduced mRNA for M2 and M3 muscarinic receptors. (urotoday.com)
  • Toll want receptor 4 (TLR4) can be an important design recognition receptor having the ability to travel Ozarelix potent innate defense responses and to modulate adaptive defense responses necessary for long term safety. (rectalcancersite.com)
  • Single nucleotide polymorphisms (SNP) of toll-like and NOD-like receptors have been associated with altered receptor activity and modified production of proinflammatory cytokines leading to a number of diseases. (sigmaaldrich.com)
  • In other cell types in the CNS, activation of Toll-like Receptor 4 (TLR4) results in activation of transcription factors such as NF-κB and AP-1, both known to induce the production of pro-inflammatory cytokines. (colorado.edu)
  • It is thought that TLR4 activation, and subsequent release of pro-inflammatory cytokines, contributes to the negative effects of tolerance, dependence, and withdrawal associated with morphine use. (colorado.edu)
  • Activated TLR4 significantly increases inflammatory cytokines and enhances cell proliferation, migration, invasion, and survival. (intechopen.com)
  • [ 194 ] Because these cytokines are elevated and circulating cerebrospinal fluid in chronic pain conditions, [ 198 , 199 ] they are possible mediators of widespread pain, as a result of widespread central sensitization (Figure 4). (medscape.com)
  • The mechanism of TLR4-mediated protection was not due to increased release of proinflammatory cytokines or changes in total numbers of immune cells recruited to the lung. (pubmedcentralcanada.ca)
  • The protection that TLR4 affords is not due to effects on secretion of proinflammatory cytokines or type I interferon, and the receptor also does not uniquely regulate recruitment of white blood cells to the site of infection. (pubmedcentralcanada.ca)
  • LYN kinase activity facilitates TLR4 - TLR6 heterodimerization and signal initiation. (rcsb.org)
  • We have found that the putative miR-107 target cyclin-dependent-kinase 6 (CDK6) expression is increased by TLR4 as a result of the decrease in miR-107. (tcd.ie)
  • No differences were apparent in phosphorylation of p38 and MAPK isoforms, but in metastatic CRC cells expressing surface TLR4 treatment with LPS increased Ser473 phosphorylation of AKT kinase. (aacrjournals.org)
  • Tie2 is a tyrosine kinase receptor located predominantly on vascular endothelial cells that plays a central role in vascular stability. (bireme.br)
  • Following activation of TLR4, in vitro/in vivo data revealed that IAXO-102 inhibited MAPK and p65 NF-kB phosphorylation associated with down regulation of the expression of TLR4 and TLR4 dependent proinflammatory proteins. (nih.gov)
  • Here, we assess variation in TLR4 expression, rather than structure, as a mechanism to diversify innate immune responses. (lu.se)
  • Compared to symptomatic patients and healthy controls, ABU patients had fewer genotype patterns, and their promoter sequence variants reduced TLR4 expression in response to infection. (lu.se)
  • CONCLUSIONS: The results suggest that genetic variation in the TLR4 promoter may be an essential, largely overlooked mechanism to influence TLR4 expression and UTI susceptibility. (lu.se)
  • RESULTS: TLR4 expression was similar in patients carrying or not carrying the variant. (jrheum.org)
  • Additional, their CD4+/CD8+ ratio is increased significantly, associated with TLR4 increasing expression. (alliedacademies.org)
  • VD is directly related with TLR4 increasing expression, which is a threat to the health of the T2DM patients. (alliedacademies.org)
  • We conducted a biomarker adjunct study nested within a randomized clinical trial (RCT) testing the effect of vitamin D, calcium, and combined treatment on the expression of the TLR4 biomarker in the stroma of normal-appearing rectal epithelium of colorectal adenoma patients. (emory.edu)
  • One hundred and five participants were recruited into the adjunct biomarker sub study and had their baseline characteristics recorded and rectal biopsies taken for TLR4 expression measurement at baseline and at year one follow-up. (emory.edu)
  • Our results indicated that neither of the treatments had a statistically significant effect on TLR4 expression in the stroma of normal-appearing rectal epithelium of colorectal adenoma patients. (emory.edu)
  • There was however a modest inverse reduction in TLR4 expression that was the most profound with vitamin D treatment. (emory.edu)
  • Vitamin D treatment reduced TLR4 expression by 18% (p = 0.394), and the combined treatment of vitamin D and calcium resulted in a 21% reduction in TLR4 expression (p = 0.425). (emory.edu)
  • Additional analyses examining the associations between baseline characteristics and TLR4 expression identified being overweight (p = 0.006), being a regular aspirin user (p = 0.046), having low total calcium intake (p = 0.033) and high vitamin D intake (p = 0.003) as factors associated with TLR4 expression in the stroma of normal-appearing rectal mucosa. (emory.edu)
  • In conclusion, supplementation with vitamin D and to a lesser extent calcium combined with vitamin D has a modest effect at lowering TLR4 expression within the stroma of normal-appearing rectal epithelium of colorectal adenoma patients. (emory.edu)
  • The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. (preprints.org)
  • There was a marked increase in the TLR4 expression and oxidative stress along with mitochondrial dysfunction in ISO group. (frontiersin.org)
  • TLR4 inhibition significantly decreased heart weight/body weight ratio and ANP, collagen, and β-MHC expression and restored the disturbed cellular antioxidant flux. (frontiersin.org)
  • The TLR4-induced hepoxilin production was also observed in primary spinal microglia, but not in astrocytes, and was accompanied by increased microglial expression of the 12/15-lipoxygenase enzyme 15-LOX-1. (nih.gov)
  • Glycosylation of Asn-526 and Asn-575 seems to be necessary for the expression of TLR4 on the cell surface and the LPS-response. (abcam.com)
  • TLR4 expression levels and cleavage or degradation products can vary between different cell and tissue samples. (abcam.com)
  • Expression levels of TLR4 and, phosphorylation of ERK and p38MAPK were higher. (lsu.edu)
  • Notably, we observed that HSM not only reduced expression of the inflammasome component NLRP1 and the P2X 7 R but also reduced the activation of caspase-4 and ATP-induced ROS production. (nature.com)
  • A mammalian homologue of Drosophila Toll receptor 4 (TLR4) was shown to induce the expression of genes involved in inflammatory responses. (researchwithrutgers.com)
  • This is the first report that shows intraocular (ciliary body and iris) expression of toll-like receptor-4, other than in cornea. (elsevier.com)
  • In contrast, the coactivation of TLR4 and IFN-γ receptors results in neuronal dysfunction and death, caused mainly by enhanced microglial inducible nitric oxide synthase (iNOS) expression and NO release, because iNOS inhibition is neuroprotective. (pnas.org)
  • However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. (nature.com)
  • Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-γ-producing Th1 response in TLR4-deficient DCs. (nature.com)
  • demonstrated which the excretory/secretory items (ESP) of could raise the appearance of TLR4 within a MyD88-unbiased way and induce the innate mucosal immunity against an infection [21]. (bio-aromatica.com)
  • Thus, activation of TLR4 in microglia in situ requires concomitant IFN-γ signaling from other host immune cells to induce neurodegeneration. (pnas.org)
  • Among this family of receptors, TLR2 and TLR4 have been most studied. (novusbio.com)
  • These studies have suggested that TLR2 and TLR4 may serve as potential main mediators of LPS signaling (4,5). (novusbio.com)
  • Single nucleotide polymorphism of toll-like receptor 4 (TLR4) is associated with juvenile spondyloarthritis in Croatian population. (sigmaaldrich.com)
  • Toll-like receptor 4 polymorphism is associated with coronary stenosis but not with the occurrence of acute or old myocardial infarctions. (biomedsearch.com)
  • Toll-like receptor 4 (TLR-4), a key mediator in activating inflammatory cascade, has an A-to-G functional polymorphism that changes aspartic acid to glycine at position 299. (biomedsearch.com)
  • TLR-4 polymorphism was not significantly associated with the occurrence of acute or old myocardial infarction (MI). (biomedsearch.com)
  • TLR4 is also activated by endogenous ligands produced by host-damaged cells and a chemo-drug paclitaxel. (intechopen.com)
  • Mitochondria, known to share many common features with prokaryotic cells, accumulate several endogenous ligands of the pattern-recognition Toll-like receptor 4 (TLR4), such as the heat shock proteins (Hsp) 70 and 60. (kent.ac.uk)
  • TLR4 specifically recognises and responds to LPS of Gram-negative bacteria and participates in both autoimmune reactions and tissue regeneration due to its ability to recognise endogenous ligands. (kent.ac.uk)
  • This study focused on oxidized LDL receptor and TLR/MD-2 complex, both express in lung endothelial cells and epithelial cells in relation with their potential endogenous ligands, S100A8 and SAA3. (nii.ac.jp)
  • NB600-662 recognizes the human Toll like receptor 4 (TLR4) cell surface antigen. (novusbio.com)
  • Toll-like Receptor 4 is a microbe associated molecular pattern receptor well known for it's sensitivity to bacterial lipopolysaccharides (LPS). (reactome.org)
  • The complex of TLR4 and its co-receptors is the primary sensor and responder to lipopolysaccharides (LPS), the major constituents of membranes of Gram-negative bacteria [ 3 ]. (intechopen.com)
  • Toll-like receptor 4 (TLR4) detects lipopolysaccharides found in most Gram-negative bacteria. (wikipedia.org)
  • TLR-4 is activated by, for example, lipopolysaccharides. (biomedsearch.com)
  • The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis. (jrheum.org)
  • ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes. (biomedsearch.com)
  • Taken together, these results indicate that ATF4 acts as a positive regulator in TLR4-triggered cytokine production. (biomedsearch.com)
  • Our aim was to determine whether SNP of TLR2 (Arg753Gln), TLR4 (Asp299Gly, Thr399Ile), and NLRP3 (Q705K) influence susceptibility to juvenile spondyloarthrtis (jSpA) and juvenile idiopathic arthritis (JIA). (sigmaaldrich.com)
  • SNP of TLR2, NLRP3, and TLR4 (Asp299Gly) were not associated with jSpA or JIA. (sigmaaldrich.com)
  • OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA). (jrheum.org)
  • A total of 155 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 210 population-based controls from the same geographical area were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. (cdc.gov)
  • TLR-4-Asp299Gly and TLR-4-Thr399Ile conferred an 1.5- and 2.6-fold increased risk of severe malaria , respectively. (bvsalud.org)
  • We also examined the effect of TLR4 signaling and its downstream mechanism in an animal model of metabolic syndrome-associated chronic kidney disease (CKD) and investigated if a blueberry-enriched diet could attenuate the progression of CKD. (lsu.edu)
  • However, it is still unclear whether PGE 2 is the central factor downstream of TLR4 signaling that promotes intestinal tumorigenesis. (elsevier.com)
  • Taken together, the results indicate that stimulation of the TLR4/MD2 complex by LPS activates PI3K/AKT signaling and promotes downstream β1 integrin function, thereby increasing the adhesiveness and metastatic capacity of CRC cells. (aacrjournals.org)
  • CONCLUSION: These data indicate the involvement of TLR-4 in the chronicity and erosive character of arthritis coincident with the antigen-specific IL-17 response. (ru.nl)
  • Neonatal cytokine responses were assessed to optimal doses of TLR2, TLR3, TLR4 and TLR9 ligands. (ersjournals.com)
  • Because of the dearth of research surrounding opioids and their effect on this cell type, this study attempted to characterize TLR4 activation in endothelial cells. (colorado.edu)
  • These data suggest that (+)-morphine induces TLR4 activation in endothelial cells and, in concert with other cell types in the central nervous system, may contribute to the negative effects of morphine use. (colorado.edu)
  • Compared with TLR4 nonexpressing, nonmetastatic CRC cells, we observed increased in vitro adherence to different extracellular matrices and human umbilical vein endothelial cells (HUVEC). (aacrjournals.org)
  • Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2 , but also partially via this receptor (PubMed:16622205). (rcsb.org)
  • The Zi Qi decoction also suppressed activation of the Toll-like receptor 4 (TLR4)-related NF-kappaB signaling pathway and subsequently inhibited the nuclear translocation of activated NF-kappaB. (medscimonit.com)
  • The combined use of TRIF and TRAM adapters is specific for TLR4 signaling pathway and leads to the induction of type I interferons and delayed activation of NFkB. (reactome.org)
  • For example, toll-like receptor 4 (TLR4) antagonism in a spontaneous 'wobbler mouse' model of ALS increased motor function, associated with a decrease in microglial activation. (biomedcentral.com)
  • Phosphodiester backbone of the CpG motif within immunostimulatory oligodeoxynucleotides augments activation of Toll-like receptor 9. (tollerant.eu)
  • Toll-like receptor 4 (TLR4) is a member of the Toll-like receptor (TLR) family, which plays a role in activation of innate immunity and pathogen recognition [ PMID: 11680785 ]. (ebi.ac.uk)
  • Recently, members of the toll-like receptor (TLR) family have been shown to be involved in recognition of the etiologic organism Plasmodium falciparum The glycosylphosphatidylinisitol anchor induces signaling in host cells via TLR-2 and -4, while hemozoin-induced immune activation involves TLR-9. (bvsalud.org)
  • 2009. Activation of TLR4-mediated NFkappaB signaling in hemorrhagic brain in rats. (springer.com)
  • Thus, the major process of thymic atrophy in this study first involved activation of transcriptional factors FOS/JUN upon LPS binding to TLR4 that caused release of inflammatory factors, thereby inducing inflammatory responses and DNA damage and ultimately cell cycle arrest and thymic injury. (biomedcentral.com)
  • The effect of NLRP3 inflammasome activation on browning was mediated by IL-1β signaling, as blocking IL-1 receptor in adipocytes protected thermogenesis. (springer.com)
  • article{c1d0477d-e10e-492e-bbfc-c9c22d6e8bae, abstract = {BACKGROUND: Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their essential coordinator role in innate immunity. (lu.se)
  • abstract = "Objective To examine the associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms (SNPs) with disease progression in rheumatoid arthritis (RA). (nebraska.edu)
  • We suggest that selective evolutionary pressure exerted by microbes expressing structurally distinguishable LPS molecules has produced the high level of variability in the Tlr4 extracellular domain. (biomedcentral.com)
  • To date, mutations in the extracellular domain of TLR4 itself, IRAK-4, NEMO (IKK gamma), and I kappa B alpha have been identified and profoundly affect the host response to infection. (nih.gov)
  • In this study, we found that TLR4/NF-κB pathway was activated by high glucose stimulation in PC12 and significantly alleviated by the co-treatment of ghrelin. (springer.com)
  • This suggests that the TLR4-MAPK signaling pathway is a key to the renal dysfunction in MetS, and BB protects against this damage by inhibiting TLR4. (lsu.edu)
  • In conclusion, GLN has a potential therapeutic effect in the protection against cardiac dysfunction mediated by sepsis through regulating the TLR4/MAPK/NF‑κB signaling pathway. (spandidos-publications.com)
  • TLR4 is weakly expressed by resting cells, but is upregulated following stimulation with LPS. (novusbio.com)
  • Furthermore, the interruption of the LPS-induced TLR4/MD-2 2:2 signaling complex formation by PIM 2 represents a previously unidentified mechanism involved in the bioactivity of PIM molecules. (pubmedcentralcanada.ca)
  • However, the mechanism by which TAK-242 inhibits TLR4 signaling after binding to TLR4 remains unknown. (aspetjournals.org)
  • Since the Vascular Dementia (VD) is one of serious complication of Type 2 Diabetes Mellitus (T2DM), we study the molecular mechanism of Toll Like Receptor 4 (TLR4) in autoimmunity respond on VD patients. (alliedacademies.org)
  • Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof. (frontiersin.org)
  • TLR4 signaling may also act as innate neuroprotective mechanism through clearance of alpha-synuclein as TLR4 ablation impairs the phagocytic response of microglia to alpha-synuclein and enhances neurodegeneration (Stefanova et al. (jax.org)
  • Filamentation appeared to be in response to a Toll-like receptor 4-mediated innate defense mechanism. (pnas.org)
  • Importantly infection is definitely closely related with cholangiocarcinoma in humans although the mechanism of this remains unfamiliar [4-6]. (bio-aromatica.com)
  • Moreover, we found that INT-HA induced an M2-like phenotype via the TLR4 receptor. (springer.com)
  • 91.7 kb), as well as the coding region and splice junctions of Tlr4 from 35 mouse ( Mus musculus ) strains, from the chimpanzee and from the baboon. (biomedcentral.com)
  • however, there is emerging evidence the innate immune system, including components of the toll-like receptor (TLR) system, may drive disease progression. (biomedcentral.com)
  • The toll-like receptor (TLR) system is one of the major components of the innate immune system, which has been implicated in ALS pathology. (biomedcentral.com)
  • As part of the innate immune system the Toll-like receptor (TLR) signaling pathway contributes to the first line of defense against microbial pathogens. (antikoerper-online.de)
  • Toll-like receptor (TLR)-4 is a member of the TLR family, which serves a vital role in the innate immune system and may be activated by LPS ( 4 ). (spandidos-publications.com)
  • Recently, human homologues of Drosophila toll, termed Toll-like receptors (TLR) 3 , have been cloned, and it is implicated that they activate both innate and adaptive immune responses in vertebrates ( 5 , 6 , 7 , 8 ). (jimmunol.org)
  • Toll-like receptors: cellular signal transducers for exogenous molecular patterns causing immune responses. (ebi.ac.uk)
  • These particles are involved in intercellular communication, modulating a wide range of signaling events during innate and acquired immune responses (Figure 1 and Table 1 ) [ 2 - 4 ]. (hindawi.com)
  • The current study assessed the effects of maternal smoking in pregnancy on neonatal toll-like-receptor (TLR)-mediated immune responses as a possible contributing factor to the elevated rates of respiratory illness. (ersjournals.com)
  • The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. (jimmunol.org)
  • The cytoplasmic region of Drosophila toll is homologous to that of the IL-1R family ( 2 ). (jimmunol.org)
  • Both Drosophila toll and IL-1R are known to signal through the NF-κB pathway ( 3 , 4 ). (jimmunol.org)
  • Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers. (preprints.org)
  • Polyinosinic-polycytidylic acid has therapeutic effects against cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via TLR3. (curehunter.com)
  • The results suggest that poly(I:C ) exerts therapeutic effects against cerebral I/R injury through the downregulation of TLR4 signaling via TLR3. (curehunter.com)
  • The high position of TLR-4 in the hierarchy of erosive arthritis provides an interesting therapeutic target for RA. (ru.nl)
  • These data establish that TLR4 mediates a protective innate immune response against vaccinia virus, which informs development of new vaccines and therapeutic agents targeted against poxviruses. (pubmedcentralcanada.ca)
  • Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. (semanticscholar.org)
  • Customers have observed this variability in WB band size and our laboratory has confirmed this variability as well observing lower molecular weight cleavage and degradation products and in some samples a lack of the full length TLR4 band. (abcam.com)
  • Statistically significant difference in genotype frequency for Thr399Ile SNP of TLR4 was observed in the jSpA (χ2 = 6.705, p = 0.035) and not in the JIA group (χ2 = 3005, p = 0.223). (sigmaaldrich.com)
  • We identified in total eight TLR4 promoter sequence variants in the Swedish control population, forming 19 haplotypes and 29 genotype patterns, some with effects on promoter activity. (lu.se)
  • Biological activity includes the ability to affect T-cell proliferation, 3 , 4 recruit natural killer T (NKT) cells, 5 , 6 , 7 activate innate receptors 6 , 8 and function as immune adjuvants. (pubmedcentralcanada.ca)
  • Interestingly, recent research demonstrates that opioids (analgesics prescribed for chronic pain) not only bind the µ-opioid receptor to confer pain relief, but also activate TLR4. (colorado.edu)
  • Here we determined the extent of genetic variation within TLR4 in a Vietnamese population and suggest that TLR4 may be involved in defense against typhoid fever in this population. (cdc.gov)
  • this interaction leads to negative regulation of TLR4 signaling (PubMed:21602844). (rcsb.org)
  • TLR2 has been shown to be a signaling receptor that is activated by LPS ( 9 , 10 ). (jimmunol.org)
  • CONCLUSION: TLR4 variant clearly reduces its potency to mediate signaling. (jrheum.org)
  • TLR4 signaling pathway has been shown to contribute to the inflammatory processes in the colon. (emory.edu)
  • In this overview, we will present current information on known mutations in the TLR4 signaling pathway that have been associated with increased susceptibility to disease. (nih.gov)
  • Poly(I:C ) downregulated TLR4 signaling via TLR3. (curehunter.com)
  • But there is no report about the biologic role of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling in controlling high glucose-induced PC12 apoptosis by ghrelin. (springer.com)
  • Therefore a better knowledge of the mechanistic information on TLR4 signaling occasions necessary for T cell priming is essential for determining and developing substances that can possibly uncouple the good adaptive immune reactions through the unfavorable or unneeded pro-inflammatory responses. (rectalcancersite.com)
  • As the TLR4/MD2 complex is expressed on CRC cells, we hypothesized that LPS may promote liver metastasis in CRC by stimulating TLR4 signaling. (aacrjournals.org)
  • Furthermore, transcriptome analysis revealed important roles for the TLR4-FOS/JUN signaling pathway in thymic injury. (biomedcentral.com)
  • Moreover, we found that the TLR4-FOS/JUN signaling pathway may play a key role in this process. (biomedcentral.com)
  • 3 4 5 6 7 Retinoschisin is almost entirely composed of a highly conserved discoidin domain frequently found in a wide range of membrane and extracellular proteins and most likely mediating cell adhesion and cellular signaling processes. (arvojournals.org)