The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
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 interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
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.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
A species of STREPTOCOCCUS isolated from pigs. It is a pathogen of swine but rarely occurs in humans.
Infections with bacteria of the genus STREPTOCOCCUS.
Diseases of domestic swine and of the wild boar of the genus Sus.
A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
A 12-kDa cysteine-rich polypeptide hormone secreted by FAT CELLS in the ADIPOSE TISSUE. It is the founding member of the resistin-like molecule (RELM) hormone family. Resistin suppresses the ability of INSULIN to stimulate cellular GLUCOSE uptake.
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Hormones released from neoplasms or from other cells that are not the usual sources of hormones.
Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.
Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.
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 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.
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.
A pattern recognition receptor that binds DOUBLE-STRANDED RNA. It mediates cellular responses to certain viral pathogens.
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 cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.
Restoration of integrity to traumatized tissue.
Common foot problems in persons with DIABETES MELLITUS, caused by any combination of factors such as DIABETIC NEUROPATHIES; PERIPHERAL VASCULAR DISEASES; and INFECTION. With the loss of sensation and poor circulation, injuries and infections often lead to severe foot ulceration, GANGRENE and AMPUTATION.
A plant genus of the family MYRSINACEAE. Members contain ardisiacrispins (oleanane triterpenoid saponins), ardicrenin, and cyclamiretin.
Hormones secreted by insects. They influence their growth and development. Also synthetic substances that act like insect hormones.
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 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.
A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).
A republic in central Africa, east of NIGER, west of SUDAN and south of LIBYA. Its capital is N'Djamena.
A family of wingless, blood-sucking insects of the suborder HETEROPTERA, including the bedbugs and related forms. Cimex (BEDBUGS), Heamatosiphon, and Oeciacus are medically important genera. (From Dorland, 28th ed)
Any method used for determining the location of and relative distances between genes on a chromosome.
Overlapping of cloned or sequenced DNA to construct a continuous region of a gene, chromosome or genome.
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.
DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes.
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)
Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.
An abnormal balloon- or sac-like dilatation in the wall of the ABDOMINAL AORTA which gives rise to the visceral, the parietal, and the terminal (iliac) branches below the aortic hiatus at the diaphragm.
Also known as articulations, these are points of connection between the ends of certain separate bones, or where the borders of other bones are juxtaposed.
The tearing or bursting of the wall along any portion of the AORTA, such as thoracic or abdominal. It may result from the rupture of an aneurysm or it may be due to TRAUMA.
An abnormal balloon- or sac-like dilatation in the wall of AORTA.
Statement of the position requirements, qualifications for the position, wage range, and any special conditions expected of the employee.
The aorta from the DIAPHRAGM to the bifurcation into the right and left common iliac arteries.
A group of compounds that contain the general formula R-OCH3.
The application of repeated, brief periods of vascular occlusion at the onset of REPERFUSION to reduce REPERFUSION INJURY that follows a prolonged ischemic event. The techniques are similar to ISCHEMIC PRECONDITIONING but the time of application is after the ischemic event instead of before.
Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173)
Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6)

Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. (1/3793)

TLR4 is a member of the recently identified Toll-like receptor family of proteins and has been putatively identified as Lps, the gene necessary for potent responses to lipopolysaccharide in mammals. In order to determine whether TLR4 is involved in lipopolysaccharide-induced activation of the nuclear factor-kappaB (NF-kappaB) pathway, HEK 293 cells were transiently transfected with human TLR4 cDNA and an NF-kappaB-dependent luciferase reporter plasmid followed by stimulation with lipopolysaccharide/CD14 complexes. The results demonstrate that lipopolysaccharide stimulates NF-kappaB-mediated gene expression in cells transfected with the TLR4 gene in a dose- and time-dependent fashion. Furthermore, E5531, a lipopolysaccharide antagonist, blocked TLR4-mediated transgene activation in a dose-dependent manner (IC50 approximately 30 nM). These data demonstrate that TLR4 is involved in lipopolysaccharide signaling and serves as a cell-surface co-receptor for CD14, leading to lipopolysaccharide-mediated NF-kappaB activation and subsequent cellular events.  (+info)

Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. (2/3793)

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. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and B cells from TLR4-deficient mice did not respond to LPS. All these manifestations were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. 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. Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-kappaB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response.  (+info)

Cutting edge: functional characterization of the effect of the C3H/HeJ defect in mice that lack an Lpsn gene: in vivo evidence for a dominant negative mutation. (3/3793)

A point mutation in the Tlr4 gene, which encodes Toll-like receptor 4, has recently been proposed to underlie LPS hyporesponsiveness in C3H/HeJ mice (Lpsd). The data presented herein demonstrate that F1 progeny from crosses between mice that carry a approximately 9-cM deletion of chromosome 4 (including deletion of LpsTlr4) and C3H/HeJ mice (i.e., Lps0 x Lpsd F1 mice) exhibit a pattern of LPS sensitivity, measured by TNF activity, that is indistinguishable from that exhibited by Lpsn x Lpsd F1 progeny and whose average response is "intermediate" to parental responses. Thus, these data provide clear functional support for the hypothesis that the C3H/HeJ defect exerts a dominant negative effect on LPS sensitivity; however, expression of a normal Toll-like receptor 4 molecule is apparently not required.  (+info)

Cutting edge: cells that carry A null allele for toll-like receptor 2 are capable of responding to endotoxin. (4/3793)

Toll-like receptor (TLR) 2 and TLR4 have been implicated in the responses of cells to LPS (endotoxin). CD14-transfected Chinese hamster ovary (CHO)-K1 fibroblasts (CHO/CD14) are exquisitely sensitive to endotoxin. Sequence analysis of CHO-TLR2, compared with human and mouse TLR2, revealed a single base pair deletion. This frameshift mutation resulted in an alternative stop codon, encoding a protein devoid of transmembrane and intracellular domains. CHO-TLR2 cDNA failed to enable LPS signaling upon transient transfection into human epithelial kidney 293 cells. Site-directed mutagenesis of CHO-TLR2 enabled expression of a presumed full-length hamster TLR2 that conferred LPS responsiveness in human epithelial kidney 293 cells. Genomic TLR2 DNA from primary hamster macrophages also contained the frameshift mutation found in CHO fibroblasts. Nevertheless, hamster peritoneal macrophages were found to respond normally to LPS, as evidenced by the induction of cytokines. These results imply that expression of TLR2 is sufficient but not essential for mammalian responses to endotoxin.  (+info)

MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. (5/3793)

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.  (+info)

Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. (6/3793)

The life-threatening complications of sepsis in humans are elicited by infection with Gram-negative as well as Gram-positive bacteria. Recently, lipopolysaccharide (LPS), a major biologically active agent of Gram-negative bacteria, was shown to mediate cellular activation by a member of the human Toll-like receptor family, Toll-like receptor (TLR) 2. Here we investigate the mechanism of cellular activation by soluble peptidoglycan (sPGN) and lipoteichoic acid (LTA), main stimulatory components of Gram-positive bacteria. Like LPS, sPGN and LTA bind to the glycosylphosphatidylinositol-anchored membrane protein CD14 and induce activation of the transcription factor NF-kappaB in host cells like macrophages. We show that whole Gram-positive bacteria, sPGN and LTA induce the activation of NF-kappaB in HEK293 cells expressing TLR2 but not in cells expressing TLR1 or TLR4. The sPGN- and LTA-induced NF-kappaB activation was not inhibited by polymyxin B, an antibiotic that binds and neutralizes LPS. Coexpression together with membrane CD14 enhances sPGN signal transmission through TLR2. In contrast to LPS signaling, activation of TLR2 by sPGN and LTA does not require serum. These findings identify TLR2 as a signal transducer for sPGN and LTA in addition to LPS.  (+info)

Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. (7/3793)

Invasive infection with Gram-positive and Gram-negative bacteria often results in septic shock and death. The basis for the earliest steps in innate immune response to Gram-positive bacterial infection is poorly understood. The LPS component of the Gram-negative bacterial cell wall appears to activate cells via CD14 and Toll-like receptor (TLR) 2 and TLR4. We hypothesized that Gram-positive bacteria might also be recognized by TLRs. Heterologous expression of human TLR2, but not TLR4, in fibroblasts conferred responsiveness to Staphylococcus aureus and Streptococcus pneumoniae as evidenced by inducible translocation of NF-kappaB. CD14 coexpression synergistically enhanced TLR2-mediated activation. To determine which components of Gram-positive cell walls activate Toll proteins, we tested a soluble preparation of peptidoglycan prepared from S. aureus. Soluble peptidoglycan substituted for whole organisms. These data suggest that the similarity of clinical response to invasive infection by Gram-positive and Gram-negative bacteria is due to bacterial recognition via similar TLRs.  (+info)

Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. (8/3793)

Expression of innate immune response proteins, including IL-1beta, TNF, and the cytokine-inducible isoform of nitric oxide synthase (iNOS), have been documented in the hearts of humans and experimental animals with heart failure regardless of etiology, although the proximal events leading to their expression are unknown. Noting that expression of a human homologue of Drosophila Toll, a proximal innate immunity transmembrane signaling protein in the fly, now termed human Toll-like receptor 4 (hTLR4), appeared to be relatively high in the heart, we examined TLR4 mRNA and protein abundance in isolated cellular constituents of cardiac muscle and in normal and abnormal murine, rat, and human myocardium. TLR4 expression levels in cardiac myocytes and in coronary microvascular endothelial cells could be enhanced by either LPS or IL-1beta, an effect inhibited by the oxygen radical scavenger PDTC. Transfection of a constitutively active TLR4 construct, CD4/hTLR4, resulted in activation of a nuclear factor-kappaB reporter construct, but not of an AP-1 or an iNOS reporter construct, in cardiac myocytes. In normal murine, rat, and human myocardium, TLR4 expression was diffuse, and presumably cytoplasmic, in cardiac myocytes. However, in remodeling murine myocardium remote from sites of ischemic injury and in heart tissue from patients with idiopathic dilated cardiomyopathy, focal areas of intense TLR4 staining were observed in juxtaposed regions of 2 or more adjacent myocytes; this staining was not observed in control myocardium. Increased expression and signaling by TLR4, and perhaps other Toll homologues, may contribute to the activation of innate immunity in injured myocardium.  (+info)

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. Previously, Cys747 in TLR4 was identified as the binding site of TAK-242. However, the mechanism by which TAK-242 inhibits TLR4 signaling after binding to TLR4 remains unknown. The present study demonstrated, using coimmunoprecipitation, that TAK-242 interferes with protein-protein interactions between TLR4 and its adaptor molecules. Among ten different human TLRs, TAK-242 selectively bound to TLR4. The time course of the inhibitory effect of TAK-242 on inflammatory mediator production corresponded to that of the binding of TAK-242 to TLR4. 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. TAK-242 inhibited the ...
Toll Like Receptor Family (TLR) - Drugs in Development, 2021 provides in depth analysis on Toll Like Receptor Family (TLR) targeted pipeline therapeutics. The report provides comprehensive information complete with Analysis by Indications, Stage of Development, Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in Toll Like Receptor Family (TLR) targeted therapeutics development and features dormant and discontinued projects. The report analyses the pipeline products across relevant therapy areas under development targeting Toll Like Receptor Family (TLR).. The report helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies ...
Background. The Toll-like receptor 4 (TLR4) is an essential component of the innate immune response to various microorganisms. We investigated the association between TLR4 polymorphism and the risk of acquiring severe infections, in patients with human immunodeficiency virus (HIV)-1 infection.. Methods. The presence of TLR4 Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs) was determined in a cohort of 199 HIV-1 infected patients and evaluated in relation to the occurrence of various infections.. Results. One hundred seventy-two patients were homozygous for the wild-type genotype; 22 patients (11%) were heterozygous for both SNPs; 4 were heterozygous for 1 polymorphism; 1 patient was heterozygous for the Asp299Gly SNP and homozygous for the Thr399Ile SNP. Of individuals with a nadir CD4 cell count of ,100 cells/mm3, those who carried both SNPs, compared with those who carried the wild-type genotype, demonstrated a ,3-fold increase in the odds ratio (OR) of any serious infection (OR, ...
Continuous inflammation in the colon often leads to chronic diseases such as inflammatory bowel disease (IBD) and colorectal cancer. Recent evidence strongly suggests the role of Toll-Like Receptors 2 and 4 in the etiology of aforementioned diseases. Therefore, pharmacological inhibition of TLR-2/TLR-4 has been a new promising strategy for preventing inflammation in IBD and colorectal cancer. 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. Ora-Curcumin is a molecular complex of curcumin with a hydrophilic polymer Eudrgit® S100 prepared by nano-precipitation. Ora-curcumin is more water soluble (~1000 times) and stable than curcumin in aqueous buffers. It is water soluble only at pHs above 6.8. Therefore, once consumed orally, it is expected to be soluble and functionally available only at the luminal side of the colon where the pH reaches 6.8. In addition, Ora-Curcumin was potent TLR-4 ...
Despite advances in its treatment, the incidence of renal diseases has been consistently increasing. Hence, there is a need to understand the underlying molecular mechanisms of the progression of kidney diseases. Recent research implicates inflammation as an important mediator of renal injury. We hypothesized that inhibiting Toll-like receptor 4 (TLR4), an upstream modulator of several inflammatory pathways, would prevent the progression of renal diseases. 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. We blocked TLR4 using gene silencing strategy in NRK52E cells. 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. We then focused on an in vivo acute kidney injury (AKI) model to elucidate the effect of TLR4 in AKI. We
Buy anti-Tlr3 antibody, Rabbit Toll-like Receptor 3 (TLR3) Polyclonal Antibody-NP_942086.1 (MBS194448) product datasheet at MyBioSource, Primary Antibodies. Application: Western Blot, Immunohistochemistry
Despite the assumption that at least some TLR family members mediate innate immune response, very little information was available regarding their expression pattern in immunocompetent cells and no functional data are available for TLR other then TLR2 and TLR4. The existence of many of them may reflect specialized functions, redundancy, and/or differential expression and roles in different cell types. Herein, we have characterized the pattern of mRNA expression of the first five TLR.. We separated fresh human monocytes, NK cells, PMN, B cells, T lymphocytes, Th1 or Th2 lymphocytes, and monocyte-derived DC. Total RNA was extracted from the cells and analyzed by Northern blot to detect specific TLR transcripts. To note, TLR1, TLR2, and TLR4 probes allowed a signal detection on the filter only after a few hours of autoradiography. On the other hand, TLR3 and TLR5 probes required at least an overnight exposure of the filter to evidence a specific transcript, suggesting that distinct TLR transcripts ...
Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury, or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4)-mediated sterile inflammation. Here we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, while its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs.
Research proven purified goat polyclonal TLR-3 (Toll-like receptor3)/CD283 antibody. Designed for immune response research. Excellent for western blotting, DIRECT Elisa and related applications.
Lipopolysaccharide (LPS) tolerance is a state of refractoriness towards a second stimulation by LPS after a preceding stimulation. LPS is recognized by Toll-like receptor-4 (TLR-4), which belongs to a group of pattern recognition receptors mediating activation of innate immunity by microbial compone …
Introduction: Toll-like receptors (TLRs) are crucial for the recognition of pathogens which subsequently lead to the activation of inflammatory pathways. However, the mycoplasma lipopeptid and TLR-2/-6 ligand MALP-2 has been used in therapeutic applications, e.g. dermal wound healing. Since tissue regeneration requires the reestablishment of a functional vascular network we investigated the impact of the TLR-2/6 ligand MALP-2 on angiogenesis and reendothelialization.. Methods and results: Expression of TLR-2 and -6 in human endothelial cells was demonstrated by PCR, Western blot and immunofluorescence and significantly up regulated after stimulation with MALP-2 (100 ng/mL, qRT-PCR, Western blot). MALP-2 induced tube formation (Matrigel, P,0.05) and endothelial cell proliferation (BrdU-incorporation, P,0.01) in vitro which could be inhibited with neutralizing antibodies against TLR-2/-6. Furthermore, MALP-2 enhanced neovascularisation of matrigel implants in mice as determined by hemoglobin ...
Ation was dependent on TLR7. Thus, despite the fact that TLR8 is expressed on MedChemExpress Crenolanib murine microglia and astrocytes, it appears to only
Objective: This paper describes a case-control study and a meta-analysis conducted to determine whether the TLR4 Asp299Gly (rs4986790) and Thr399Ile (..
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Sigma-Aldrich offers abstracts and full-text articles by [Rong Chen, Liqiang Feng, Mo Ruan, Xinghui Liu, Sahil Adriouch, Hua Liao].
TLR10 - TLR10 (untagged)-Human toll-like receptor 10 (TLR10), transcript variant 1 available for purchase from OriGene - Your Gene Company.
TLR2 antibody (toll-like receptor 2) for ELISA, IHC-P, WB. Anti-TLR2 pAb (GTX31279) is tested in Human, Mouse samples. 100% Ab-Assurance.
摘 要:Toll样受体4(TLR4)是固有免疫系统中能够识别病原相关分子模式的受体家族成员,可识别革兰氏阴性菌的脂多糖(LPS)而在细菌感染性疾病的发生中起重要作用。近年来越来越多的研究发现,TLR4还广泛参与病毒感染性疾病的发生和病毒的免疫逃逸,由于其信号转导通路的独特性和细胞定位的可变性,再次引起人们极大的研究兴趣。该文将介绍TLR4的生物学特性、信号转导通路及TLR4与病毒感染的最新研究进展 ...
Laborator Synevo. Informatii generale. Principalele roluri ale interleukinelor de tip 1 (IL-1), considerate cel mai important reglator al raspunsului imun si inflamator al organismului, se refera la inducerea unor evenimente asociate, precum sinteza reactantilor de faza acuta, casexia si febra. Pentru descrierea mecanismelor de modulare a acestor functii sunt vizate in principal cele 3 interleukine de tip 1 care se pot lega de 2 tipuri de receptori: citokinele IL-1α, IL-1b si IL-1RA (din familia receptorilor de tip IL-1/Toll-like receptor) si receptorii IL-1RI si IL-1RII. Caracteristicile functionale ale acestor citokine si receptori difera, determinand consecinte variate, necesare modularii efectelor, astfel: -IL-1α si IL-1b sunt citokinele active biologic, cu structuri si roluri similare, reglate insa diferit;. -IL-1RA (engl. IL-1 receptor antagonist) este, in fapt, un antagonist natural al receptorului pentru IL-1;. -IL-1α se poate lega doar de IL-1RI, iar IL-1b si IL-1RA se pot lega de ...
Antiviral inte immunity depends on the combition of parallel pathways triggered by virus detecting proteins in the Toll-like receptor (TLR) family and…
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TLR2 (толл-подобный рецептор 2, CD282) - мембранный белок, входящий в группу толл-подобных рецепторов, обеспечивающих функционирование врождённого иммунитета. TLR2 так же как TLR1 распознаёт патоген-связанные молекулярные структуры грам-положительных бактерий, включая пептидогликаны, липотейхоевую кислоту, некоторые компоненты микобактерий и зимозан клеточной стенки дрожжей. ...
TY - JOUR. T1 - Different roles of TiR8/Sigirr on toll-like receptor signaling in intrarenal antigen-presenting cells and tubular epithelial cells. AU - Lech, M.. AU - Garlanda, C.. AU - Mantovani, A.. AU - Kirschning, C. J.. AU - Schlöndorff, D.. AU - Anders, H. J.. PY - 2007/7. Y1 - 2007/7. N2 - Toll-like receptors (TLRs) exist on both myeloid and intrinsic renal cells contributing to the initiation of innate immunity during renal infection with uropathogenic Escherichia coli. Toll-interleukin 1 receptor (IL-1R) (TIR)8/SIGIRR is an orphan receptor of the TLR/IL-1R family, which suppresses TLR signaling of immune cells and is highly expressed in the kidney. Lack of TIR8/SIGIRR is associated with enhanced renal chemokine signaling upon exposure to lipopolysaccharide (LPS). This was because of TIR8/SIGIRR expression on resident intrarenal myeloid cells rather than tubular epithelial cells which express it on basolateral and luminal membranes. The lack of TIR8/SIGIRR does not enhance TLR/IL-1R ...
Oh, Djin-Ye; Baumann, Konstantin; Hamouda, Osamah; Eckert, Jana K; Neumann, Konrad; Kücherer, Claudia; Bartmeyer, Barbara; Poggensee, Gabriele; Oh, Nari; Pruss, Axel; Jessen, Heiko; Schumann, Ralf R Abstract Objectives: Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens. TLR7 recognizes RNA of various viruses including HIV. The objective of this study…
BACKGROUND: Inflammation and matrix degradation are the hallmarks of high-risk atherosclerosis that leads to myocardial infarction and stroke. Toll-like receptors (TLRs), key players in innate immunity, are upregulated in atherosclerotic lesions, but their functional role in human atherosclerosis is unknown. We explored the effects of blocking TLR-2, TLR-4, and myeloid differentiation primary response gene 88 (MyD88), a signaling adaptor shared by most TLRs and interleukin-1 receptor (IL-1R), in an in vitro model of human atherosclerosis. METHODS AND RESULTS: Carotid endarterectomies were obtained from patients with symptomatic carotid disease. Cells were isolated via enzymatic tissue dissociation and cultured in the presence or absence of TLR signaling blockers. A dominant-negative form of MyD88 (MyD88(DN)) decreased the production of monocyte chemotactic protein-1/CCL2 (P=0.000), IL-8/CXCL8 (P=0.006), IL-6 (P=0.002), matrix metalloproteinase-1 (MMP-1; P=0.002), and MMP-3 (P=0.000), as well as nuclear
We provide evidence that cationic lipids, usually considered as a safe alternative to viral vectors as nanocarriers for gene therapy or drug intracellular delivery, do not behave as inert material but do activate cellular signalling pathways implicated in inflammatory reactions. We show here that the cationic lipid RPR206252 induces NF-kappa B activation, and the production of TNF-alpha, IL-1 beta, IL-6 and IFN-gamma by human or mouse macrophage cell lines. Further, we demonstrate that the activation of inflammatory cascades by RPR206252 is dependent on Toll-like receptor 2 (TLR2), the natural sensor of bacterial lipopeptides and NOD-like receptor protein 3 (NLRP3), the major inflammasome component. Our results suggest that cationic lipid nanocarriers because of their ability to stimulate the innate system can be used as a new class of synthetic and safe adjuvant for vaccination. From the Clinical Editor: Cationic lipid nanocarriers are typically considered neutral tools for gene delivery. However, as
Upon ligand engagement, TLRs elicit an intracellular signaling cascade that eventually leads to the expression of genes encoding antimicrobial, inflammatory, and immunomodulatory proteins [1]. Through a focused effort, four TLR adaptor proteins containing TIR homology domains were identified about ten years ago and demonstrated to play specific roles in the activation of TLR signaling [2], [3], [4], [5], [6], [7], [8]. The TIR adaptors enable signaling through TLRs by interacting with the TIR domain in the cytoplasmic tail of TLRs [1]. Among the 10 human TLRs, all except TLR3 are dependent on the TIR adaptor protein MyD88 (myeloid differentiation primary response gene 88) for signaling [1]. The MyD88 pathway activates the transcription factor NF‐κB to induce pro‐inflammatory gene expression. On the other hand, TLR3 depends on TRIF (TIR‐domain‐containing adapter inducing IFN‐β) for downstream signaling, and TLR4 can signal both through MyD88 and TRIF. Like the MyD88 pathway, the TRIF ...
The recent discovery of an ancient family of toll-like receptors (TLRs) in the immune system has substantially enhanced the potential for a variety of therapies, for both failing immune systems, which leaves the body open to infection or over-active ones, which can lead to chronic inflammation. Signaling by Toll-Like Receptors provides a comprehensive review of important techniques in molecular biology, cell biology, biochemistry, genetics, and immunology and their critical application to the study of toll-like receptor structure, biological function, and the intracellular signaling triggered by these receptors, as well as the high promise for uncovering effective pharmaceutica ...
Anthracycline antibiotics are inducers of an immunogenic form of apoptosis that has immunostimulatory properties because of the release of damage-associated molecular patterns. To study the mechanisms used by the innate immune system to sense this immunogenic form of cell death, we established an in vivo model of cell death induced by intraperitoneal injection of doxorubicin, a prototype of anthracyclines. The acute sterile inflammation in this model is characterized by rapid influx of neutrophils and increased levels of IL-6 and monocyte chemotactic protein-1. We demonstrate that acute inflammation induced by doxorubicin is associated with apoptosis of monocytes/macrophages and that it is specific for doxorubicin, an immunogenic chemotherapeutic. Further, the inflammatory response is significantly reduced in mice deficient in myeloid differentiation primary response gene 88 (MyD88), TLR-2 or TLR-9. Importantly, a TLR-9 antagonist reduces the recruitment of neutrophils induced by doxorubicin. By ...
TY - JOUR. T1 - Toll-like receptor 2 (TLR2)-TLR9 crosstalk dictates IL-12 family cytokine production in microglia. AU - Holley, Monica M.. AU - Zhang, Yongqing. AU - Lehrmann, Elin. AU - Wood, William H.. AU - Becker, Kevin G.. AU - Kielian, Tammy L. PY - 2012/1/1. Y1 - 2012/1/1. N2 - Microglia are the resident mononuclear phagocytes of the CNS parenchyma and represent an initial line of defense against invading microorganisms. Microglia utilize Toll-like receptors (TLRs) for pathogen recognition and TLR2 specifically senses conserved motifs of gram-positive bacteria including lipoproteins, lipoteichoic acids, and peptidoglycan (PGN) leading to cytokine/chemokine production. Interestingly, primary microglia derived from TLR2 knockout (KO) mice over-expressed numerous IL-12 family members, including IL-12p40, IL-12p70, and IL-27 in response to intact S. aureus, but not the less structurally complex TLR2 ligands Pam3CSK4 or PGN. The ability of intact bacteria to augment IL-12 family member ...
This Bovine Toll-like receptor 3 (TLR3) ELISA Kit employs a two-site sandwich ELISA to quantitate TLR3.,TLR3; CD283;,TLR 3 is a member of the Toll-like receptor family of pattern recognition receptors of the innate immune system. Discovered in 2001,TLR3 recognizes double-stranded RNA, a form of genetic information carried by some viruses such as reoviruses. Upon recognition, TLR 3 induces the activation of NF-kB to increase production of type I interferons which signal other cells to increase their antiviral defenses. Double-stranded RNA is also recognised by the cytoplasmic receptors RIG-I and MDA-5.The structure of TLR3 was reported in June 2005 by researchers at The Scripps Research Institute. TLR3 forms a large horseshoe shape that contacts with a neighboring horseshoe, forming a
Specific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors identified as homologs of Toll in Drosophila. Mammalian TLRs are expressed on innate immune cells, such as macrophages and dendritic cells, and respond to the membrane components of Gram-positive or Gram-negative bacteria. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. TLR signaling pathways are separated into two groups: a MyD88-dependent pathway that leads to the production of proinflammatory cytokines with quick activation of NF-{kappa}B and MAPK, and a MyD88-independent pathway associated with the induction of IFN-beta and IFN-inducible genes, and maturation of dendritic cells with slow activation of NF-{kappa}B and MAPK. Source: KEGG:Toll-like Receptor Signaling ...
In response to ligand binding to the Toll-like receptor 4 (TLR4) and myeloid differentiation-2 (MD-2) receptor complex, two major signaling pathways are activated that involve different adaptor proteins. One pathway depends on myeloid differentiation marker 88 (MyD88), which elicits proinflammatory responses, whereas the other depends on Toll-IL-1 receptor (TIR) domain-containing adaptor inducing interferon-β (TRIF), which elicits type I interferon production. Here, we showed that the TLR4 agonist and vaccine adjuvant CRX-547, a member of the aminoalkyl glucosaminide 4-phosphate (AGP) class of synthetic lipid A mimetics, displayed TRIF-selective signaling in human cells, which was dependent on a minor structural modification to the carboxyl bioisostere corresponding to the 1-phosphate group on most lipid A types. CRX-547 stimulated little or no activation of MyD88-dependent signaling molecules or cytokines, whereas its ability to activate the TRIF-dependent pathway was similar to that of a ...
TY - JOUR. T1 - Toll-like receptor modulation in cardiovascular disease. T2 - A target for intervention?. AU - Földes, Gábor. AU - von Haehling, Stephan. AU - Anker, Stefan D.. PY - 2006/8. Y1 - 2006/8. N2 - Toll-like receptors (TLRs) form a family of pattern recognition receptors that have emerged as key mediators of innate immunity. These receptors sense invading microbes and initiate the immune response. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical disorders. Among the processes in which TLRs play a role are cardiovascular disorders such as cardiac ischaemia, coronary artery disease, ventricular remodelling, cancer angiogenesis or transplant rejection. From these, many important opportunities for disease modification through TLR signalling manipulation can be imagined. Their role as potential targets for therapeutic intervention is just beginning to be appreciated and this article reviews the current status of these ...
The innate immune system is the first line of defense against invading pathogens. Recognition of microbial ligands by the innate immune system relies on germ-line encoded, evolutionarily conserved receptors called pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are one such family of PRRs and are involved in innate defenses to a variety of microbes. At the core of TLR signaling pathways are Toll interleukin-1 receptor (TIR) domain containing adapter proteins. Much of the specificity of TLR pathways arise from the differential use of these adapter proteins. The TLR signaling cascade that ensues upon ligand recognition is marked by finely orchestrated molecular interactions between the receptor and the TIR domain containing adapter proteins, as well as various downstream kinases and effector molecules. Conserving the structural integrity of the TLR components is thus essential for maintaining a robust host defense system. Sometimes, changes in a protein can be brought about by single
Toll-like receptors are pattern-recognition receptors that have key roles in detecting microbes and initiating inflammatory responses. Recently, a host of new microbial products that activate specific Toll-like receptors have been defined, and additional components that mediate intracellular signali …
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to circumvent innate immunity was demonstrated (Cirl et al. 2008, Nature Medicine 14, 399-406). This involves a bacterial TIR domain-containing protein (Tcp) that is secreted by bacterial pathogens and inhibits Toll-like receptor (TLR) signalling. ,p, Toll-like receptors have a central role in innate immunity. They recognise molecules from microbial pathogens and trigger an immune response through a signalling domain called TIR. Bacterial Tcps contain a TIR domain that mimics the TIR domain of Toll-like receptors. TLR signalling is interrupted when MyD88, a downstream component of TLR signalling, binds to the TIR domain of a bacterial Tcp instead of to the TIR domain of a Toll-like receptor. This way, secreted Tcps impair the release of cytokines and, subsequently, prevent an inflammatory response. ,p, Our data show that bacterial Tcps or the TIR domains contained in Tcps can be used to modulate cytokine responses of innate immune cells as is desirable in the treatment of autoimmune diseases. ...
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. 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. 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). We classified the compounds active on TLR4 pathway depending on the specific molecular targets (LPS, LBP, CD14, MD-2 or TLR4). Small molecules developed by our group are described that inhibit LPS-stimulated TLR4 activation by selectively targeting the LPS-CD14 interaction. These compounds ...
FREE FULLTEXT Lester, Richard T; Yao, Xiao-Dan; Ball, T Blake; McKinnon, Lyle R; Kaul, Rupert; Wachihi, Charles; Jaoko, Walter; Plummer, Francis A; Rosenthal, Kenneth L Free Access Article Outline Abstract Objectives: Toll-like receptors (TLR) are important in pathogen recognition and may play a role in HIV disease. We evaluated the effect of chronic untreated and…
The innate immune system detects highly conserved, relatively invariant structural motifs of pathogens. Toll-like receptors (TLRs) have been identified as the primary innate immune receptors. TLRs distinguish between different patterns of pathogens and activate a rapid innate immune response; however, TLRs can also be activated by host-derived molecules. In addition to being expressed in immune cells, TLRs are expressed in other tissues, such as those of the cardiovascular system. TLRs could, therefore, be a key link between cardiovascular disease development and the immune system. Indeed, evidence that TLR activation contributes to the development and progression of atherosclerosis, cardiac dysfunction in sepsis, and congestive heart failure, is convincing. Although much has been learned about TLR activation in cellular components of the cardiovascular system, the role individual TLR family members have in the pathophysiology of cardiovascular diseases and hence in clinical practice remains to be
Genital inflammation is associated with increased HIV acquisition risk. Induction of an inflammatory response can occur through the recognition of pathogenic or commensal microbes by Toll-like receptors (TLRs) on various immune cells. We used a in vitro peripheral blood mononuclear cell (PBMC) system to understand the contribution of TLR stimulation in inducing inflammation and the activation of target T cells, and its effect on HIV susceptibility. PBMCs were stimulated with TLR agonists LPS (TLR4), R848 (TLR7/8), and Pam3CSK4 (TLR1/2), and then infected with HIV NL4-3 AD8. Multiplexed ELISA was used to measure 28 cytokines in cell culture supernatants. Flow cytometry was used to measure the activation state (CD38 and HLA-DR), and CCR5 expression on CD4+ and CD8+ T cells. Although TLR agonists induced higher cytokine and chemokine secretion, they did not significantly activate CD4+ and CD8+ T cells and showed decreased CCR5 expression relative to the unstimulated control. Despite several classes of
In his studies, he used proteinase-producing fungi as the environmental trigger for asthma. Laboratory mice that lacked toll-like receptor 4 did not mount a robust allergic airway disease when challenged by proteinase, viable fungi or other triggers but did have a normal Th2 immunity.. Why do our bodies do this? said Corry. The answer is both simple and complicated. The system developed to allow organisms to survive infection with deadly organisms such as fungi. How it achieves that is complicated.. In this survival mode, the immune system generates symptoms that can themselves create disease.. Against the insidious onslaught of organisms such as fungi, which can kill if left unchecked, asthma may be a better alternative, said Corry.. If you don¹t fight fungi off, they will get you, he said.. Others who took part in this research include Valentine Ongeri Millien, Wen Lu, Joanne Shaw, Xiaoyi Yuan, Garbo Mak, M.D., Luz Roberts, Li-Zhen Song J. Morgan Knight, Chad J. Creighton, Amber Luong, ...
Toll-like receptor 4 (TLR4), along with its accessory protein myeloid differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically recognizes lipopolysaccharides (LPS), which are present on the cell wall of Gram-negative bacteria, activating the innate immune response. Some TLR4 modulators are undergoing preclinical and clinical evaluation for the treatment of sepsis, inflammatory diseases, cancer and rheumatoid arthritis. Since the relatively recent elucidation of the X-ray crystallographic structure of the extracellular domain of TLR4, research around this fascinating receptor has risen to a new level, and thus, new perspectives have been opened. In particular, diverse computational techniques have been applied to decipher some of the basis at the atomic level regarding the mechanism of functioning and the ligand recognition processes involving the TLR4/MD-2 system at the atomic level. This review summarizes the reported molecular modeling and computational studies that ...
Toll-like receptor 2 (TLR2)is a member of the TLR family, which plays a central role in the innate immune response to a wide variety of microorganisms. Animal studies have shown thatTLR2-knockout mice are more susceptible to septicemia due to Staphylococcus sure us and Listeria monocyto genes,meningitis due to Streptococcus pneumoniae,and infection with Mycobacterium tuberculosis,suggesting that functional TLR2polymorphisms may impair host response to a certain spectrum of microbial pathogens. In humans, 2 polymorphisms in the exon part of TLR2, which attenuatereceptor signaling, enhance the risk of acute severe infections, tuberculosis, and leprosy. Because gram-positive bacteria have became the first cause of severe infections, including septic shock, knowledge of the role that alteration or lack of TLR2function plays in the pathogenesis of infectious diseases could contribute to the design of new the rapeuticstrategies, including prevention, pharmacologicalintervention, and vaccine ...
To locate the ligand binding site on TLR3, we analyzed ,50 mutations within the TLR3-ECD. Remarkably, only 2 of the 50 residues tested resulted in abrogation of both the activation of TLR3 by pI:pC and the direct binding of pI:pC to purified TLR3-ECD protein. These two residues, H539 and N541, are conserved from zebrafish to humans (Fig. 10, which is published as supporting information on the PNAS web site) and position the ligand binding site on the glycan-free surface of the ECD at LRR20.. Replacing His-539 with an alanine has little effect on TLR3 responsiveness, whereas substitution of a negatively charged carboxyl group for an imidazole ring at this site results in a total loss of function. This finding suggests that a negative charge from a backbone phosphate group on dsRNA occupies a position in close proximity to residue 539 in the ligand-receptor complex. In the WT protein a protonated imidazole ring of His-539 would neutralize the negative charge of the phosphate, but in the H539E ...
CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology. The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ
As we learn more about the biology of the Toll-like receptors (TLRs), a wide range of molecules that can activate this fascinating family of pattern recognition receptors emerges. In addition to conserved pathogenic components, endogenous danger signals created upon tissue damage are also sensed by TLRs. Detection of these types of stimuli results in TLR mediated inflammation that is vital to fight pathogenic invasion and drive tissue repair. Aberrant activation of TLRs by pathogenic and endogenous ligands has also been linked with the pathogenesis of an increasing number of infectious and autoimmune diseases, respectively. Most recently, allergen activation of TLRs has also been described, creating a third broad class of TLR stimulus that has helped to shed light on the pathogenesis of allergic disease. To date, microbial activation of TLRs remains best characterized. Each member of the TLR family senses a specific subset of pathogenic ligands, pathogen associated molecular patterns (PAMPS), and a
Atherosclerosis is an inflammatory disease with a strong involvement of innate immunity. Toll-like receptors (TLRs) are the best-characterized pattern recognition receptors of the innate immune system. Almost all cell types in lesions, inflammatory leukocytes and resident vascular cells alike express TLRs. TLRs are able to sense modified lipids, enhance foam cell formation, induce leukocyte recruitment, and increase cytokine and matrix metalloproteinase production within atherosclerotic lesions. As such, TLRs represent an important link between atheroma and inflammation, making them attractive targets for the treatment of cardiovascular disease. Novel TLR-specific biologics are being developed and tested in other inflammatory diseases. This article will describe the exciting potential of TLRs as therapeutic targets for the treatment of atherosclerosis and will also highlight the potential challenges in the clinical application of TLR-based therapeutics in cardiovascular disease.
Statins enhance toll-like receptor 4-mediated cytokine gene expression in astrocytes: implication of Rho proteins in negative feedback regulation.: Toll-like re
The immunosuppressive microenvironment in tumors hampers the induction of antitumor immunity by vaccines or immunotherapies. Toll-like receptor (TLR) ligands have the potential to treat tumors, but they can exert a mixture of positive and negative effects on inflammation in the tumor
Atherosclerosis is the underlying cause of coronary artery disease and cerebrovascular disease. Risk prediction of cardiovascular disease and subsequent clinical manifestations are mainly based on models including hypercholesterolemia and smoking, but these models do not always work on an individual level. Therefore, there is an urgent need for biomarkers. Atherosclerosis ... read more is considered an inflammatory disease in which innate immune cells like monocytes and neutrophils play a prominent role. Toll-like receptors (TLRs), which are abundantly expressed by these cells, are important receptors for the activation of the immune system. These receptors respond to exogenous ligands derived from pathogens, but also to endogenous triggers. Ligand binding to TLRs results in the transcription of pro-inflammatory and pro-atherogenic mediators like cytokines and increased expression of cell adhesion molecules, but it has also been reported that repetitive TLR stimulation results in attenuated TLR ...
A Novel Chinese Medicine, Xinfeng Capsule, Modulates Proinflammatory Cytokines via Regulating the Toll-Like Receptor 4 (TLR4)/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Kappa B (NF-κB) Signaling Pathway in an Adjuvant Arthritis Rat Model - Add Comment #916317
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Toll Like Receptor 1 (TLR1) in samples from tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species ...
Fli-l is a member of the Ets family of transcription factors whose role has been defined in a variety of cellular populations. It plays a role in the development and function of a wide array of immune cells, and plays a critical role in the development of endothelial cells. Fli-l has also been implicated in the pathogenesis of SLE; patients with SLE expressed significantly higher levels of Fli-l in their peripheral blood lymphocytes than did healthy patients, and murine models of SLE, such as the MRLllpr model, also expressed higher levels of Fli-l in their peripheral blood lymphocytes than did normal strains of mice. Conclusive evidence linking Fli-l overexpression to SLE development was shown in a transgenic mouse model, where 2-3 fold overexpression of Fli-l resulted in the development of an autoimmune disease similar to SLE. Currently, Fli-l s possible roles in the innate immune response have not been explored. This study aimed to identify possible roles for Fli-l in the innate immune ...
The IUPHAR/BPS Guide to Pharmacology. TLR2 - Toll-like receptor family. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
This review aims to summarize the latest efforts performed in the search for novel chemical entities such as Toll-like receptor (TLR) modulators by means of virtual screening techniques. This is an emergent research field with only very recent (and successful) contributions. Identification of drug-like molecules with potential therapeutic applications for the treatment of a variety of TLR-regulated diseases has attracted considerable interest due to the clinical potential. Additionally, the virtual screening databases and computational tools employed have been overviewed in a descriptive way, widening the scope for researchers interested in the field.
TY - JOUR. T1 - Signatures of balancing selection in toll-like receptor (TLRs) genes - novel insights from a free-living rodent. AU - Kloch, Agnieszka. AU - Wenzel, Marius A.. AU - Laetsch, Dominik R.. AU - Michalski, Olek. AU - Bajer, Anna AU - Behnke, Jerzy M.. AU - Welc-Falȩciak, Renata. AU - Piertney, Stuart B.. N1 - Correction to: Scientific Reports https://doi.org/10.1038/s41598-018-26672-2, published online 30 May 2018 The work was supported by grant no. DEC-2012/07/B/NZ8/00058 from the Polish National Science Centre to A.K. Field studies were funded by grant MNiI 2P04C09827 „Badania naturalnych źródeł zarażenia mikropasożytów patogennych dla człowieka to AB. We are thankful to Dr. hab W. Babik who provided access to an Illumina MiSeq platform, and to K. Dudek who prepared the Nextera library. Special thanks to A. Biedrzycka for her valuable comments on the final version of the manuscript. We also would like to thank two anonymous reviewers for their valuable comments that ...
Toll-like Receptors (TLRs) are not only crucial for the initiation of immune response, but also play a key role in several inflammatory diseases. This..
Toll-like receptor 9 (TLR9), a naturally existing immune regulatory site, not only takes part in enhancing anti-tumor immunity but also promoting the ..
This webpage describes Toll-Like Receptors present in mice and humans and their corresponding ligands, adapter proteins, and accessory molecules. The website also provides a comprehensive distribution list of TLRs expression in both mouse and human cells. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
This webpage describes Toll-Like Receptors present in mice and humans and their corresponding ligands, adapter proteins, and accessory molecules. The website also provides a comprehensive distribution list of TLRs expression in both mouse and human cells. BioLegend develops and manufactures world-class, cutting-edge immunological reagents for biomedical research, offered at an outstanding value.
Effect of a Mushroom (Coriolus versicolor) Based Probiotic on the Expression of Toll-like Receptors and Signal Transduction in Goat Neutrophils
BOMFIM, G. F.... Toll-like receptor 4 inhibition reduces vascular inflammation in spontaneously hypertensive rats. Life Sciences 122 n. p. 1-7 FEB 1 2015. Artigo Científico.
Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-,IMG SRC=/math/kgr.gif ALT={kappa} BORDER=0, ...
Home , Papers , Lysozyme elicits pain during nerve injury by neuronal Toll-like receptor 4 activation and has therapeutic potential in neuropathic pain. ...
邓守龙.,Kun Yu.,Qian Wu.,Yan Li.,Xiao-Sheng Zhang.,...&连正兴.(2016).Toll-Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep.Oxidative Medicine and Cellular Longevity,2016,Article No. 9151290 ...
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Akira, S; Takeda K (2004). "Toll-like receptor signalling". Nat Rev Immunol. 4 (7): 499-511. doi:10.1038/nri1391. PMID 15229469 ... Like many neuronal receptors, Dscam proteins have multiple functions, with repulsive and attractive roles that are dependent on ... Dong, YM; Taylor HE; Dimopoulos G (2006). "AgDscam, a hypervariable immunoglobulin domain-containing receptor of the Anopheles ... its structure as an Ig receptor related to other cell adhesion molecules (CAMs). The DSCAM gene has been identified in the DS ...
... is a member of the toll-like receptor family of pattern recognition receptors of the innate immune system. TLR3 is a ... Toll-like receptor 3 (TLR3) also known as CD283 (cluster of differentiation 283) is a protein that in humans is encoded by the ... "Entrez Gene: toll-like receptor 3". Norval M (2012). "Virus-Cell Interactions". In Greenwood D, Slack RC, Barer MR, et al. (eds ... Pan LN, Zhu W, Li Y, Xu XL, Guo LJ, Lu Q, Wang J (2014). "Astrocytic Toll-like receptor 3 is associated with ischemic ...
"Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". Journal of Immunology. 170 (7): 3565 ... TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor ( ... Pålsson-McDermott EM, O'Neill LA (2004). "Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4". ... Toll-like receptor 4 has been shown to be important for the long-term side-effects of opioid analgesic drugs. Various μ-opioid ...
Another set comprises pattern recognition receptors such as toll-like receptors, which induce the production of interferons and ... Uematsu S, Akira S (May 2007). "Toll-like receptors and Type I interferons". The Journal of Biological Chemistry. 282 (21): ... which became a popular subject after the discovery of the Toll receptor system in Drosophila, a previously marginal organism ... and the receptors that recognize antigens must be produced in a huge variety of configurations, in essence one receptor (at ...
Toll-like receptor 5, also known as TLR5, is a protein which in humans is encoded by the TLR5 gene. It is a member of the toll- ... "Toll-like receptors". Critical Care Medicine. 30 (1 Suppl): S1-11. doi:10.1097/00003246-200201001-00001. PMID 11782555. Toll- ... "Entrez Gene: TLR5 toll-like receptor 5". Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. (April 2001). "The ... August 2003). "Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B ...
"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 ... a toll-like receptor 4 antagonist, in patients with severe sepsis". Critical Care Medicine. 38 (1): 72-83. doi:10.1097/CCM. ...
Ten toll-like receptors have been described in humans. Cells in the innate immune system have pattern recognition receptors, ... Three major classes of these "cytosolic" receptors are NOD-like receptors, RIG (retinoic acid-inducible gene)-like receptors, ... Toll-like receptors were first discovered in Drosophila and trigger the synthesis and secretion of cytokines and activation of ... Botos I, Segal DM, Davies DR (April 2011). "The structural biology of Toll-like receptors". Structure. 19 (4): 447-59. doi: ...
Convergent evolution in European and Rroma populations: pressure exerted by plague on Toll-like receptors. Proc Nat Acad Sci ... Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J ... 15.7) 2002-2005 Junior researcher grant "The role of Toll-like receptors for recognition of Candida albicans" (250.000 euro) ... "Novel antagonists of the toll-like receptor 4". Retrieved 11 September 2020. Profile at the Radboud University Profile at ...
Kaisho T, Akira S (February 2002). "Toll-like receptors as adjuvant receptors". Biochimica et Biophysica Acta (BBA) - Molecular ... Toll-like receptor 8 is a protein that in humans is encoded by the TLR8 gene. TLR8 has also been designated as CD288 (cluster ... "Entrez Gene: TLR8 toll-like receptor 8". Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H ... Peng G, Guo Z, Kiniwa Y, Voo KS, Peng W, Fu T, Wang DY, Li Y, Wang HY, Wang RF (August 2005). "Toll-like receptor 8-mediated ...
ATIs are part of the plant's natural defense against insects and may cause toll-like receptor 4 (TLR4)-mediated intestinal ... "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 ... 128 (4 Suppl 1): S68-73. doi:10.1053/j.gastro.2005.02.015. PMID 15825129. Lundin KE, Wijmenga C (Sep 2015). "Coeliac disease ...
ATIs are part of the plant's natural defence against insects and may cause toll-like receptor 4 (TLR4)-mediated intestinal ... "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 ... This permeating effect is secondary to the binding of specific undigestible gliadin fragments to the CXCR3 chemokine receptor ...
"Toll-like receptor control of the adaptive immune response" (PDF). Nature Immunology. Nature Publishing Group. Archived from ... According to Google Scholar, one of her publications, "Toll-like receptor control of the adaptive immune response," has been ... Iwasaki, A.; Medzhitov, R. (2004). "Toll-like receptor control of the adaptive immune responses". Nature Immunology. 5 (4): 987 ... Retrieved 4 May 2015. "Six Yale professors elected to National Academy of Sciences". yale.edu. May 1, 2018. Retrieved December ...
... due to the presence of immune receptors called toll-like receptors (TLRs) that are expressed on the membranes of leukocytes ... Toussi DN, Massari P (Apr 2014). "Immune Adjuvant Effect of Molecularly-defined Toll-Like Receptor Ligands". Vaccines. 2 (2): ... Takeda K, Akira S (January 2005). "Toll-like receptors in innate immunity". International Immunology. 17 (1): 1-14. doi:10.1093 ... Mouse studies question importance of toll-like receptors to vaccines". Science. 314 (5807): 1859-60. doi:10.1126/science. ...
Toll-like receptor signaling pathway - Reference pathway (KO) from the KEGG website. TRIF+protein,+human at the US National ... Toll-like receptors (TLRs) recognize specific components of microbial invaders and activate an immune response to these ... TIR-domain-containing adapter-inducing interferon-β (TRIF) is an adapter in responding to activation of toll-like receptors ( ... Palsson-McDermott, Eva M.; O'Neill, Luke A. J. (2004). "Signal transduction by the lipopolysaccharide receptor, Toll-like ...
Members of interleukin-1 receptor (Il-1R) and the Toll-like receptor superfamily share an intracytoplasmic Toll-IL-1 receptor ( ... March 2006). "Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the toll-like receptor 6-1-10 ... or Toll-like receptor-mediated immune responses (TLR), but was not essential to T-cell Receptor (TCR) signalling as was ... The Toll-Like Receptors (TLRs) are stimulated by recognition of pathogen-associated molecular patterns (PAMPS), whereas members ...
... dysregulates a number of targets which are mostly involved in toll-like receptor pathways that bring about a cytokine ... Quinn SR, O'Neill LA (Jul 2011). "A trio of microRNAs that control Toll-like receptor signalling". International Immunology. 23 ... 123 (4): 631-40. doi:10.1016/j.cell.2005.10.022. PMID 16271387. S2CID 16973870. Sonkoly E, Ståhle M, Pivarcsi A (Apr 2008). " ... 60 (4): 1035-41. doi:10.1002/art.24404. PMC 2670476. PMID 19333945. Lánczky, András; Nagy, Ádám; Bottai, Giulia; Munkácsy, ...
Toll‐like receptor 4‐mediated activation of murine mast cells. Journal of leukocyte biology. 2001 Dec;70(6):977-84. Cited 235 ... Cutting edge: distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human ... her lab also has a special interest in toll-like receptors in mucosal immune regulation. Marshall attended high school in ... Her early work characterizing the role of the histamine receptor on mast cells has now become relevant to the context of cancer ...
... is one of the toll-like receptors and plays a role in the immune system. TLR2 is a membrane protein, a receptor, which is ... Toll-like receptor 2 also known as TLR2 is a protein that in humans is encoded by the TLR2 gene. TLR2 has also been designated ... The following ligands have been reported to be agonists of the toll-like receptor 2: TLR 2 has been shown to interact with TLR ... The protein encoded by this gene is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen ...
January 2010). "Evidence that opioids may have toll-like receptor 4 and MD-2 effects". Brain, Behavior, and Immunity. 24 (1): ... 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 ... August 2012). "Opioid activation of toll-like receptor 4 contributes to drug reinforcement". The Journal of Neuroscience. 32 ( ...
Carvalho A, Pasqualotto AC, Pitzurra L, Romani L, Denning DW, Rodrigues F (February 2008). "Polymorphisms in toll-like receptor ... such as defects to toll-like receptor (TLR) 4, IL1 and IL15, TLR3, TLR10, TREM1, VEGFA, DENND1B, and PLAT. The full underlying ... 63 (4): e1-e60. doi:10.1093/cid/ciw326. PMC 4967602. PMID 27365388. For patients receiving triazole-based therapy for IA, ... 63 (4): e1-e60. doi:10.1093/cid/ciw326. PMC 4967602. PMID 27365388. Denning DW. "Clinical manifestations and diagnosis of ...
Moncada DM, Kammanadiminiti SJ, Chadee K (July 2003). "Mucin and Toll-like receptors in host defense against intestinal ... increasing receptor activity and the growth of cancer cells. MUC1 also prevents the interaction of immune cells with receptors ... Li Y, Ren J, Yu W, Li Q, Kuwahara H, Yin L, Carraway KL, Kufe D (September 2001). "The epidermal growth factor receptor ... This allows cancer cells which produce a large amount of MUC1 to concentrate growth factors near their receptors, ...
... is principally a PDE4 inhibitor but has also been shown to act as an antagonist at the toll-like receptor 4 (TLR4). ... 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): ... 21 (4): 895-903. doi:10.1111/adb.12261. PMC 4644513. PMID 25975386. Bell RL, Lopez MF, Cui C, Egli M, Johnson KW, Franklin KM, ...
... role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling". Journal of ... role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling". Journal of ... It is an inhibitory adaptor protein within Toll-like receptors (TLR). The TLR pathway is a part of the innate immune system ... Bulut Y, Faure E, Thomas L, Equils O, Arditi M (July 2001). "Cooperation of Toll-like receptor 2 and 6 for cellular activation ...
Receptor for Advanced Glycation End-products) and Toll-like receptors (TLRs). Release from cells seems to involve two distinct ... Some actions of HMGB1 are mediated through the toll-like receptors (TLRs). Interaction between HMGB1 and TLR4 results in ... HMGB1 released from tumour cells was demonstrated to mediate anti-tumour immune responses by activating Toll-like receptor 2 ( ... "A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release". ...
CpG motif DNA acts via the pattern recognition receptor, toll-like receptor 9, found highly expressed in PDCs and B cells. The ... Marshak-Rothstein A (November 2006). "Toll-like receptors in systemic autoimmune disease". Nature Reviews Immunology. 6 (11): ... 4 (5): 290-5. doi:10.1186/ar426. PMC 128938. PMID 12223102. Cerutti ML, Centeno JM, Goldbaum FA, de Prat-Gay G (2001). " ... 13 Suppl 4: 16-22, discussion 38. doi:10.1046/j.1365-2036.1999.00027.x. PMID 10597335. S2CID 1642477. Hyrich KL, Silman AJ, ...
"Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". Journal of Immunology. 170 (7): 3565 ... "Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". Journal of Immunology. 170 (7): 3565 ... In innate immunity, the MyD88 plays a pivotal role in immune cell activation through Toll-like receptors (TLR), which belong to ... Arancibia SA, Beltrán CJ, Aguirre IM, Silva P, Peralta AL, Malinarich F, Hermoso MA (2007). "Toll-like receptors are key ...
"ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance". Nature ... O'Neill, Luke A. J.; Bowie, Andrew G. (2007). "The family of five: TIR-domain-containing adaptors in Toll-like receptor ... Liew, Foo Y.; Xu, Damo; Brint, Elizabeth K.; O'Neill, Luke A. J. (2005). "Negative regulation of Toll-like receptor-mediated ... Palsson-McDermott, Eva M.; O'Neill, Luke A. J. (2004). "Signal transduction by the lipopolysaccharide receptor, Toll-like ...
Homeostasis in the intestine requires stimulation of toll-like receptors by commensal microbes. When mice are raised in germ- ... For example, the human symbiont Bacteroides fragilis produces polysaccharide A (PSA), which binds to toll-like receptor 2 (TLR- ... Bashir, Mohamed Elfatih H.; Louie, Steve; Shi, Hai Ning; Nagler-Anderson, Cathryn (2004-06-01). "Toll-like receptor 4 signaling ... "The Toll-like receptor pathway establishes commensal gut colonization". Science. 332 (6032): 974-977. doi:10.1126/science. ...
"Toll-like receptors (TLR2 and TLR4) recognize polysaccharides of Pseudallescheria boydii cell wall". Carbohydrate Research. 356 ... 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 ... 25 (4): 896-907. doi:10.1086/515532. PMID 9356805. Rippon, John Willard (1988). Medical mycology : the pathogenic fungi and the ...
... a role for Toll-like receptors". Nature Reviews. Microbiology. 8 (4): 296-307. doi:10.1038/nrmicro2321. PMC 3037727. PMID ... B cells can internalize antigen that binds to their B cell receptor and present it to helper T cells. Unlike T cells, B cells ... T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells. ... This is achieved by interacting with a professional APC which presents an antigen recognized by their T cell receptor. The APC ...
Toll-like receptor 4 (TLR4) is a member of the Toll-like receptor (TLR) family, which plays a role in activation of innate ... GO:0034142 toll-like receptor 4 signaling pathway Molecular Function. GO:0001875 lipopolysaccharide receptor activity GO: ... Toll-like receptors: cellular signal transducers for exogenous molecular patterns causing immune responses.. Int. J. Med. ... Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression ...
Toll-Like Receptors (TLRs) are the innate immunity receptors that play an activating role when interacting with molecules ... T. Kawai and S. Akira, "The role of pattern-recognition receptors in innate immunity: update on toll-like receptors," Nature ... E. M. Palsson-McDermott and L. A. J. ONeill, "Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4," ... Natural Products with Toll-Like Receptor 4 Antagonist Activity. Monica Molteni, Annalisa Bosi, and Carlo Rossetti ...
Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4.. Pålsson-McDermott EM1, ONeill LA. ... Toll-like receptor; ΤRΑF6, tumour necrosis factor receptor-associated factor; TRIF, TIR-containing adapter molecule; TRAM, TRIF ... Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS - Toll-like ... This aids the loading of LPS onto the LPS receptor complex, which is composed of dimerized TLR4 receptors and two molecules of ...
Toll like receptor-4 expression in lipopolysaccharide induced lung inflammation.. Janardhan KS1, McIsaac M, Fowlie J, ... Bacterial lipopolysaccharides (LPS) initiate immune response through Toll-like receptor 4 (TLR4). Because many a times host is ...
... which attenuates receptor signaling and diminishes the inflammatory response to gram-negative pathogens, is associated with a ... Toll-like receptor 4 polymorphisms and atherogenesis N Engl J Med. 2002 Jul 18;347(3):185-92. doi: 10.1056/NEJMoa012673. ... We determined whether recently discovered genetic variants of toll-like receptor 4 (TLR4) that confer differences in the ... Conclusions: The Asp299Gly TLR4 polymorphism, which attenuates receptor signaling and diminishes the inflammatory response to ...
... Shoulong Deng,1 Kun Yu,2,3 Qian Wu,4 Yan Li,3 ... Toll-like receptor 4 (TLR4) is an important sensor of Gram-negative bacteria and can trigger activation of the innate immune ... 4School of Biological Science and Medical Engineering, Beijing University of Aeronautics and Astronautics, Beijing 100191, ...
The intestinal expression of the lipopolysaccharide receptor TLR4, which is higher in the premature compared with full-term ... as inhibition of STAT3 or IL-17 receptor signaling attenuated NEC in mice, while IL-17 release impaired enterocyte tight ... Human data are representative of 6 individuals for flow cytometry, 4 individuals for immunohistochemistry, and 6 for cytokine ...
... Summary According to the recently published report Toll Like Receptor 4 - ... Toll Like Receptor 4 (hToll or CD284 or TLR4) - Toll-like receptor 4 is a protein encoded by the TLR4 gene. This receptor is ... Toll Like Receptor 4 - Pipeline Review, H1 2020. Summary. According to the recently published report Toll Like Receptor 4 - ... The report assesses Toll Like Receptor 4 (hToll or CD284 or TLR4) targeted therapeutics based on mechanism of action (MoA), ...
... including Toll-like receptors (TLRs), RIG-I-like receptors, NOD-like receptors and C-type lectin receptors, recognize distinct ... Toll-like receptor 4 confers inflammatory response to Suilysin. Lili Bi1,2†, Yaya Pian1†, Shaolong Chen1, Zhiqiang Ren1, Peng ... Citation: Bi L, Pian Y, Chen S, Ren Z, Liu P, Lv Q, Zhang Y, Zhang S, Hao H, Yuan Y and Jiang Y (2015) Toll-like receptor 4 ... 2003). Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc. Natl. Acad. Sci. ...
Within the CNS, pattern recognition receptors, such as toll-like receptors (TLRs), can serve this sentinel role identifying " ... Opioid Activation of Toll-Like Receptor 4 Contributes to Drug Reinforcement. M. R. Hutchinson, A. L. Northcutt, T. Hiranita, X. ... Opioid Activation of Toll-Like Receptor 4 Contributes to Drug Reinforcement. M. R. Hutchinson, A. L. Northcutt, T. Hiranita, X. ... the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of ...
Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med 2010;14(6B):1419-1431pmid: ... Central Resistin Overexposure Induces Insulin Resistance Through Toll-Like Receptor 4. Yacir Benomar, Arieh Gertler, Pamela De ... Central Resistin Overexposure Induces Insulin Resistance Through Toll-Like Receptor 4. Yacir Benomar, Arieh Gertler, Pamela De ... Loss-of-function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 2007;56:1986- ...
... and stable cell-surface receptors related to the Drosophila gene toll that thus are referred to as Toll-like receptors (TLRs) ( ... Toll-Like Receptor 4 Is Involved in Subacute Stress-Induced Neuroinflammation and in the Worsening of Experimental Stroke ... Blockade of Toll-Like Receptor 4 Attenuates Morphine Tolerance and Facilitates the Pain Relieving Properties of Morphine ... Spinal Cord Toll-Like Receptor 4 Mediates Inflammatory and Neuropathic Hypersensitivity in Male But Not Female Mice ...
In response to ligand binding to the Toll-like receptor 4 (TLR4) and myeloid differentiation-2 (MD-2) receptor complex, two ... Selective TRIF-Dependent Signaling by a Synthetic Toll-Like Receptor 4 Agonist ... Selective TRIF-Dependent Signaling by a Synthetic Toll-Like Receptor 4 Agonist ... Selective TRIF-Dependent Signaling by a Synthetic Toll-Like Receptor 4 Agonist ...
Thrombomodulin promotes diabetic wound healing by regulating toll-like receptor 4 expression.. [Tsung-Lin Cheng, Chao-Han Lai, ... In this study, we demonstrated that expressions of TM and Toll-like receptor 4 (TLR4) were both downregulated in high-glucose ...
This article focuses on the possible mechanisms involved in it.Toll like receptors (TLRs) comprise a large family of the ... pathogen-pattern recognition receptors (PPRR) originally identified in Drosophila in the mid 1990s as a Toll protein (1). In ... Drosophila, it was found to be involved in the resistance against fungal infections (2). The first human homolog for the Toll ... Toll-Like Receptor 4 in Inflammation and Angiogenesis: A Double-Edged Sword ...
Our data suggest that TLR-4 might be a novel target in the treatment of rheumatoid arthritis. ... we demonstrate for the first time that inhibition of TLR-4 suppresses the severity of experimental arthritis and results in ... Inhibition of Toll-like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis Arthritis Rheum. 2007 Sep; ... matrix of cartilage leads to the production of molecules capable of activating the immune system via Toll-like receptor 4 (TLR- ...
"Toll-like receptor 4 is not required for the Th2 response itself," said Corry. "But, the Th2 response is proteinase dependent. ... Other work in the field pointed to another immune molecule called toll-like receptor 4 that was believed to play a role in ... The pathway to asthma winds through Toll-like receptor 4. February 13, 2017. by Gady Goldsobel ... Receptor protein in the brain controls the bodys fat rheostat. *Panic Disorder Symptoms May Be Tied to Acid-Sensing Receptor ...
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.. ...
Facchini, F.A., Di Fusco, D., Barresi, S. et al. Effect of chemical modulation of toll-like receptor 4 in an animal model of ... Effect of chemical modulation of toll-like receptor 4 in an animal model of ulcerative colitis. *Fabio Alessandro Facchini1. , ... Kagan JC, Su T, Horng T, Chow A, Akira S, Medzhitov R (2008) TRAM couples endocytosis of toll-like receptor 4 to the induction ... Cario E (2010) Toll-like receptors in inflammatory bowel diseases: a decade later. Inflamm Bowel Dis 16:1583-1597 ...
Toll-like receptor 4 restricts retinal progenitor cell proliferation. Ravid Shechter, Ayal Ronen, Asya Rolls, Anat London, ... Toll-like receptor 4 and CD14 expression in human ciliary body and TLR-4 in human iris endothelial cells. Exp. Eye Res. 79:203- ... Toll-like receptor 4 restricts retinal progenitor cell proliferation. Ravid Shechter, Ayal Ronen, Asya Rolls, Anat London, ... The expression of Toll-like receptor 4 (TLR4) has been recently documented in the ciliary body of the mammalian eye (Brito et ...
Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 ... Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial ... is recruited to the Toll/interleukin (IL)-1 receptor (TIR) domain of the TLR4 receptor (11). The interaction between TLR4 and ... Inhibition or deletion of the lipopolysaccharide receptor Toll-like receptor-4 confers partial protection against lipid-induced ...
Toll-Like Receptor 4 Is Essential in the Development of Abdominal Aortic Aneurysm.. [Chao-Han Lai, Kuan-Chieh Wang, Fang-Tzu ... Toll-like receptor (TLR) family plays a key role in innate immunity and various inflammatory responses. TLR4, one of the well- ... characterized pattern-recognition receptors, can be activated by endogenous damage-associated molecular pattern molecules such ...
Toll-like receptor 4-activated B cells out-compete Toll-like receptor 9-activated B cells to establish peripheral immunological ... Toll-like receptor 4-activated B cells out-compete Toll-like receptor 9-activated B cells to establish peripheral immunological ... Activation of B cells by Toll-like receptor (TLR) agonists modulates B cell maturation and alters T-cell-dependent B-cell ... LPS-induced maturation of B cells can be redirected by B-cell receptor cross-linking toward a tolerogenic phenotype, ...
Recent advances on Toll-like receptor 4 modulation: new therapeutic perspectives. Author(s): Lenny Zaffaroni, Francesco Peri ... Computational Approaches to Toll-Like Receptor 4 Modulation. Author(s): Jean-Marc Billod, Alessandra Lacetera, Joan Guzmán- ... The Role of Carbohydrates in the Lipopolysaccharide (LPS)/Toll-Like Receptor 4 (TLR4) Signalling. Author(s): Florent Cochet, ... Toll-Like Receptor 4 activation and function in diseases: an integrated chemical-biology approach.. ...
... Stewart C.R., Stuart L ... Here we show that oxidized LDL and amyloid-beta trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 ... a common receptor for these disparate ligands. Our results identify CD36-TLR4-TLR6 activation as a common molecular mechanism ... and 6. Assembly of this newly identified heterodimer is regulated by signals from the scavenger receptor CD36, ...
Toll-like receptors (TLRs) are a cornerstone of vertebrate innate immunity. In this study, we identified orthologues of TLR4, ... The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 456:658-662. doi: 10.1038/ ... Molecular cloning and functional characterization of chicken Toll-like receptors-a single chicken toll covers multiple ... Brownlie R, Allan B (2011) Avian Toll-like receptors. Cell Tissue Res 343:121-130. doi: 10.1007/s00441-010-1026-0 PubMed ...
Keywords: major depressive disorder, innate immune, toll-like receptor, anxiety ... toll-like receptor 4 (TLR4) mRNA expression level was associated with severity of major depressive disorder (MDD) evaluated ... Association between toll-like receptor 4 expression and symptoms of major depressive disorder Ming-Kung Wu,1 Tiao-Lai Huang,1,2 ... Kai-Wei Huang,3 Ya-Ling Huang,1 Yi-Yung Hung1,4 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang ...
High glucose induces toll-like receptor expression in human monocytes: mechanism of activation. Diabetes 2008; 57: 3090- 3098. ... Differential Effects of Cream, Glucose, and Orange Juice on Inflammation, Endotoxin, and the Expression of Toll-Like Receptor-4 ... Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in ... Differential Effects of Cream, Glucose, and Orange Juice on Inflammation, Endotoxin, and the Expression of Toll-Like Receptor-4 ...
... whether the anti-inflammatory effects of sevoflurane postconditioning were mediated via inhibition of the toll-like receptor ( ... The necrotic cell counts and expression levels of TLR-4, NF-κB, caspase-3, and TNF-α in brain tissue as well as serum levels of ... Our findings suggest that the anti-inflammatory actions of sevoflurane postconditioning via inactivation of the TLR-4/NF-κB ... TLR)-4/nuclear factor kappa B (NF-κB) pathway after global transient cerebral ischemia in rats. Forty-five rats were randomly ...
It has become apparent that signaling through toll-like receptors (TLRs), the receptor family recognizing pathogen-associated ... and induction of specific ligands for epidermal growth factor receptor (EGFR). These two pathways are closely involved with ... It has become apparent that signaling through toll-like receptors (TLRs), the receptor family recognizing pathogen-associated ... toll-like receptor; prostaglandin; inflammation; innate immunity colitis; colitis-associated cancer; bacteria; toll-like ...
  • 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)
  • In particular, Toll-Like Receptor 4 (TLR4) has been described to be involved in the inflammatory processes observed in several pathologies (such as ischemia/reperfusion injury, neuropathic pain, neurodegenerative diseases, and cancer). (hindawi.com)
  • Toll-Like Receptor 4 (TLR4) belongs to the family of pattern recognition receptors (PRRs), conserved receptors of innate immunity, homologues of the Drosophila Toll protein, discovered to be important for the defense against microbial infections. (hindawi.com)
  • TLR4) can detect the presence of virtually any gram-negative bacterial infection [ 4 ]. (hindawi.com)
  • Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS - Toll-like receptor 4 (TLR4) - but also in a better appreciation of the complexity of the signalling pathways activated by LPS. (nih.gov)
  • Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD-2, was described. (nih.gov)
  • This aids the loading of LPS onto the LPS receptor complex, which is composed of dimerized TLR4 receptors and two molecules of the extracellular adapter MD-2. (nih.gov)
  • Bacterial lipopolysaccharides (LPS) initiate immune response through Toll-like receptor 4 (TLR4). (nih.gov)
  • We determined whether recently discovered genetic variants of toll-like receptor 4 (TLR4) that confer differences in the inflammatory response elicited by bacterial lipopolysaccharide are related to the development of atherosclerosis. (nih.gov)
  • The Asp299Gly TLR4 polymorphism, which attenuates receptor signaling and diminishes the inflammatory response to gram-negative pathogens, is associated with a decreased risk of atherosclerosis. (nih.gov)
  • Toll-like receptor 4 (TLR4) is an important sensor of Gram-negative bacteria and can trigger activation of the innate immune system. (hindawi.com)
  • The intestinal expression of the lipopolysaccharide receptor TLR4, which is higher in the premature compared with full-term human and mouse intestine, is required for lymphocyte influx through TLR4-mediated upregulation of CCR9/CCL25 signaling. (jci.org)
  • Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14 , LY96 and TLR4 (PubMed:11274165). (rcsb.org)
  • Toll Like Receptor 4 (hToll or CD284 or TLR4) pipeline Target constitutes close to 44 molecules. (reportlinker.com)
  • Toll Like Receptor 4 (hToll or CD284 or TLR4) - Toll-like receptor 4 is a protein encoded by the TLR4 gene. (reportlinker.com)
  • It also reviews key players involved in Toll Like Receptor 4 (hToll or CD284 or TLR4) targeted therapeutics development with respective active and dormant or discontinued projects. (reportlinker.com)
  • Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. (jneurosci.org)
  • Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. (jneurosci.org)
  • Moreover, recent studies have provided evidence for the contribution of Toll-like receptor-4 (TLR4) in the pathogenesis of obesity and insulin resistance. (diabetesjournals.org)
  • We show that in the CNS, specific activation of innate immunity through a Toll-like receptor 4 (TLR4)-dependent pathway leads to neurodegeneration. (pnas.org)
  • TLR4 functions as the signal-transducing receptor for the endotoxin lipopolysaccharide (LPS) ( 10 ), which is a major component of the outer membrane of Gram-negative bacteria. (pnas.org)
  • We show that microglia are the major cells in the CNS that express TLR4 and that cortical neurons do not express this receptor. (pnas.org)
  • In response to ligand binding to the Toll-like receptor 4 (TLR4) and myeloid differentiation-2 (MD-2) receptor complex, two major signaling pathways are activated that involve different adaptor proteins. (sciencemag.org)
  • Here, we showed that the TLR4 agonist and vaccine adjuvant CRX-547, a member of the aminoalkyl glucosaminide 4-phosphate (AGP) class of synthetic lipid A mimetics, displayed TRIF-selective signaling in human cells, which was dependent on a minor structural modification to the carboxyl bioisostere corresponding to the 1-phosphate group on most lipid A types. (sciencemag.org)
  • In this study, we demonstrated that expressions of TM and Toll-like receptor 4 (TLR4) were both downregulated in high-glucose cultured human keratinocytes and in skin keratinocytes of diabetic patients. (sigmaaldrich.com)
  • TLR4 signaling is implicated in the innate immune responses against a wide-range of microbes, including Gram-negative and -positive bacteria, mycobacteria, spirochetes, yeasts, and some viruses such as respiratory syncytial viruses (RSV) and mammary tumor viruses ( 4 ). (frontiersin.org)
  • TLR4 is a type I transmembrane protein characterized by an extracellular domain containing leucine-rich repeats (LRRs) and a cytoplasmic tail harboring a conserved region known as Toll/IL-1 receptor (TIR) domain. (frontiersin.org)
  • TLR4, along with its two co-receptors, the myeloid differentiation antigen (MD2) and the LRR protein CD14, forms a trimeric receptor that is involved in the recognition of lipopolysaccharide (LPS). (frontiersin.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)
  • Considering the pivotal role played by toll-like receptors (TLRs) in gut inflammation, we evaluate here the therapeutic effect of the synthetic glycolipid TLR4 antagonist FP7. (springer.com)
  • FP7 strongly reduced the inflammatory responses induced by lipopolysaccharide (LPS) in vitro, due to its capacity to compete with LPS for the binding of TLR4/MD-2 receptor complex thus inhibiting both the MyD88- and TRIF-dependent inflammatory pathways. (springer.com)
  • Cario E, Podolsky DK (2000) Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. (springer.com)
  • Consistent with this hypothesis, FFAs have been shown to bind to toll-like receptor (TLR)4 ( 4 ), a transmembrane receptor, and TLR4-driven inflammatory cascades, such as the inhibitor of κB (IκB)/nuclear factor κB (NFκB) pathway, are implicated in the pathogenesis of insulin resistance ( 5 - 7 ). (diabetesjournals.org)
  • TLR4 functions as the receptor for lipopolysaccharide (LPS) of gram-negative bacterial cell walls ( 8 ). (diabetesjournals.org)
  • After LPS binds to TLR4, and its co-receptors CD14 and MD-2, the adaptor protein myeloid differentiation factor 88 (MyD88) is recruited to the Toll/interleukin (IL)-1 receptor (TIR) domain of the TLR4 receptor ( 11 ). (diabetesjournals.org)
  • TLR4, one of the well-characterized pattern-recognition receptors, can be activated by endogenous damage-associated molecular pattern molecules such as high mobility group box 1 (HMGB1) to sustain sterile inflammation. (sigmaaldrich.com)
  • However, LPS-induced maturation of B cells can be redirected by B-cell receptor cross-linking toward a tolerogenic phenotype, demonstrating that tolerogenic B cells can be induced by TLR4 activation ( 21 ). (pnas.org)
  • In our previous study, toll-like receptor 4 (TLR4) mRNA expression level was associated with severity of major depressive disorder (MDD) evaluated with the 17-item Hamilton Depression Rating Scale (HAMD-17). (dovepress.com)
  • Toll-like receptor 2 (TLR2) and TLR4 play important roles in the early innate immune response to microbial challenge. (jci.org)
  • To clarify the functional roles of TLRs 2 and 4 in mast cells, we examined bone marrow-derived mast cells (BMMCs) from TLR2 or TLR4 gene-targeted mice. (jci.org)
  • We then focused on TLR4, the other Toll-like receptor that signals through TRIF. (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)
  • 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)
  • It has recently been shown that MMTV activates B cells via Toll-like receptor 4 (TLR4), a molecule involved in innate immune responses. (asm.org)
  • Here, we show that direct virus binding to TLR4 induced maturation of bone marrow-derived dendritic cells and up-regulated expression of the MMTV entry receptor (CD71) on these cells. (asm.org)
  • The mRNA level of Toll-like receptor 4 (TLR4) was determined by semiquantitative reverse transcriptase-polymerase chain reaction. (unboundmedicine.com)
  • These data are consistent with TLR4 being the major receptor for MyD88-induced effects on AngII-induced AAAs. (ahajournals.org)
  • Indeed, a synergistic relationship between TLR4/MD-2 and TLR7/9 has been recently reported in the triggering of IL-12 and other Th1-promoting cytokines by DCs ( 3 , 4 ). (rupress.org)
  • We previously reported that Toll-like receptor-2 (TLR2) agonists induce expression of a more limited repertoire of pro-inflammatory genes than TLR4 agonists. (portlandpress.com)
  • TLR4-induced IFN-β mRNA was found to be MyD88- and PKR (double-stranded RNA-dependent protein kinase)-independent, but TIRAP (Toll/interleukin-1 receptor domain-containing adapter protein)/Mal (MyD88-adapter-like)-dependent. (portlandpress.com)
  • The anti-osteoclastogenic function of HA was dependent on Toll-like receptor 4 (TLR4) but not on CD44. (biologists.org)
  • Our results clearly show that HA inhibits osteoclast differentiation through TLR4 by interfering with M-CSF signaling, and point that the interaction between ECM components and innate immune receptors can play an important role in the regulation of bone metabolism. (biologists.org)
  • Recent studies have suggested that Toll-like receptor 4 (TLR4) might play a role in neuropathic pain. (medsci.org)
  • Peritoneal macrophages obtained from Toll-like receptor 4 (TLR4) mutant mice exhibited marked attenuation of TNFα production in response to saturated FAs. (ahajournals.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 aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL. (biomedsearch.com)
  • Post‐reperfusion inflammation and an up‐regulation of toll‐like receptor 4 (TLR4), an upstream sensor of innate immunity, are associated with poor outcome in stroke patients. (bps.ac.uk)
  • Toll-like Receptor-4 (TLR4) is a key component of the innate immune response during bacterial infections. (arvojournals.org)
  • Toll-like receptor 4 (TLR4), along with its accessory protein myeloid differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically recognizes lipopolysaccharides (LPS), which are present on the cell wall of Gram-negative bacteria, activating the innate immune response. (altmetric.com)
  • Since the relatively recent elucidation of the X-ray crystallographic structure of the extracellular domain of TLR4, research around this fascinating receptor has risen to a new level, and thus, new perspectives have been opened. (altmetric.com)
  • This review summarizes the reported molecular modeling and computational studies that have recently provided insights into the mechanism regulating the activation/inactivation of the TLR4/MD-2 system receptor and the key interactions modulating the molecular recognition process by agonist and antagonist ligands. (altmetric.com)
  • Toll-Like Receptor 4 Promoter Polymorphisms: Common TLR4 Variants May Protect against Severe Urinary Tract Infection. (lu.se)
  • METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the TLR4 promoter (4,3 kb) in Swedish blood donors. (lu.se)
  • Our results affirm that exogenous RONS can initiate the production of resolvin D1 by concurrently increasing the expression of its biosynthetic enzymes and its receptor through TLR4 stimulation. (umsystem.edu)
  • Apoptosis‑related proteins, toll‑like receptor 4 (TLR4) protein and NF‑κB translocation were examined by western blotting. (spandidos-publications.com)
  • Toll-like receptor 4 (TLR4) is an innate immunity pattern recognition receptor, which initiates the immune response and oxidative damage by activating NF-κB, a crucial proinflammatory transcription factor ( 9 , 10 ). (spandidos-publications.com)
  • Subsequent receptor screening determined TLR4 as a receptor mediating the PSD-induced proinflammatory response. (harvard.edu)
  • Furthermore, berberine also suppressed the toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (Myd88)/nuclear factor (NF)-κB signaling pathway which was activated during the conversion of THP-1 cells to macrophages by PMA. (spandidos-publications.com)
  • Toll-like receptor 4 (TLR4), an intensively investigated member of the TLR family, serves a critical role in initiating inflammation ( 9 ) and participates in mediating inflammatory cell formation ( 10 ). (spandidos-publications.com)
  • Toll-like receptor 4 (TLR4) initiates a complex signalling pathway when it interacts with lipopolysaccharide (LPS), which ultimately results in a proinflammatory response. (bmj.com)
  • Using two different models of acute pancreatitis, we investigated how genetic deletion of TLR4 or its co-receptor CD14 effects its progression and severity. (bmj.com)
  • The severity of acute pancreatitis is ameliorated in mice that lack either TLR4 or CD14 receptors. (bmj.com)
  • describe the results of in vitro and in vivo experiments that point to circulating dengue virus non-structural protein 1 (NS1) and the innate immune Toll-like receptor 4 (TLR4) as a focus for basic scientists as well as vaccine and drug developers. (sciencemag.org)
  • HMGB1 activates the pattern recognition receptor, toll-like receptor 4 (TLR4), and induces sterile inflammation. (ahajournals.org)
  • Of the mouse strains deficient in putative receptors and co-regulator for HMGB1 (TLR4-/-, TLR2-/-, RAGE-/- and CD14-/-), TLR4-/- mice showed the greatest inhibition of IH after injury. (ahajournals.org)
  • 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)
  • 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)
  • Using macrophages from mice lacking TLR2 and/or TLR4, CD14, or CD44, we demonstrated that the pro-autophagy signal required TLR4 interaction with CD44, a receptor involved in adhesion, migration, lymphocyte activation, and angiogenesis. (fraunhofer.de)
  • Thus, CD44 is a novel signaling co-receptor for biglycan, an interaction that is required for TLR4-CD44-dependent pro-autophagic activity in macrophages. (fraunhofer.de)
  • Emerging evidence suggests that oxidant-induced Toll-like receptor 4 (TLR4) activation plays a major role in "sterile" inflammation. (ovid.com)
  • Toll-like receptor 4 (TLR4) recognizes specific structural motifs associated with microbial pathogens and also responds to certain endogenous host molecules associated with tissue damage. (ovid.com)
  • In vitro experiments confirmed that lack of TLR4 is sufficient to influence macrophage activation status in response to classical polarizing stimuli such as IFN-gamma and IL-4. (ovid.com)
  • This review highlights aims to provide a narrative for the involvement of Toll-like receptor (TLR4) in the development of chemotherapy-induced GI mucositis, an already emerging theme within this field. (deepdyve.com)
  • In the current study, we demonstrate that E. cuniculi infection causes strong Toll-like receptor 4 (TLR4)-dependent dendritic cell activation and a blockade of this molecule reduces the ability of DC to prime an antigen-specific CD8 + T-cell response. (asm.org)
  • The functional variant (Asp299gly) of toll-like receptor 4 (TLR4) influences TLR4-mediated cytokine production in rheumatoid arthritis. (jrheum.org)
  • OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA). (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)
  • Since Toll-like receptor 2 (TLR2), TLR4, and TLR9 activation have been involved in HIV-1 recrudescence, we sought to determine the role of these TLRs in HIV-1 reactivation induced by the periodontal pathogens Fusobacterium nucleatum and Porphyromonas gingivalis using BF24 monocytes/macrophages stably transfected with the HIV-1 promoter driving chloramphenicol acetyltransferase (CAT) expression and THP89GFP cells, a model of HIV-1 latency. (asm.org)
  • In this study, we have sought to test the hypothesis that the Toll-like receptor 4 (TLR4) induced transcription patterns elicited in humans exposed to in vivo endotoxin would parallel gene expression patterns observed in trauma patients with initial non-infectious injury. (springermedizin.de)
  • We found a link between the delayed clearance of bacteria from the lung and a large part of chromosome 4 in F2 mice with a maximum log of the odds score of 33.6 at 65.4 Mb, which is the location of Tlr4. (synbiosis.com)
  • Toll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. (biomedcentral.com)
  • 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)
  • Toll-like receptor 4 (TLR4) promotes the production of pro-inflammatory cytokines associated with cancer chemoresistance. (biomedcentral.com)
  • These molecules activate members of the Toll-like receptor (TLR) family, of which TLR4 is the receptor for bacterial lipopolysaccharide (LPS). (biomedcentral.com)
  • Toll-like receptor 4 (TLR4) is a key proximal signaling receptor responsible for initiating the innate immune response. (biomedcentral.com)
  • Bacterial antigens like LPSs are recognized by innate immunity receptors such as Toll-like receptor 4 (TLR4), associated with LPS receptor (CD14). (ru.nl)
  • Toll like receptor 4 (TLR4) is an innate immune receptor that binds a wide spectrum of exogenous (lipopolysaccharide) and endogenous ligands. (fapesp.br)
  • 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)
  • Increased expression of toll-like receptor 4 (TLR4) and its endogenous ligands, is characteristic of rheumatoid arthritis (RA) synovitis. (listlabs.com)
  • Toll-Like Receptors (TLRs) are the innate immunity receptors that play an activating role when interacting with molecules released by bacteria and viruses (PAMPs, pathogen-associated molecular patterns) or with molecules released by injured cells and tissues (DAMPs, danger-associated molecular patterns). (hindawi.com)
  • The PRRs, including Toll-like receptors (TLRs), RIG-I-like receptors, NOD-like receptors and C-type lectin receptors, recognize distinct microbial components to activate immune cells ( Takeuchi and Akira, 2010 ). (frontiersin.org)
  • Cells of the innate immune system recognize invariant molecular structures of pathogens termed pathogen-associated molecular patterns through a series of genetically conserved and stable cell-surface receptors related to the Drosophila gene toll that thus are referred to as Toll-like receptors (TLRs) ( 9 ). (pnas.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. (frontiersin.org)
  • Toll-like receptors (TLRs) are a cornerstone of vertebrate innate immunity. (springer.com)
  • It has become apparent that signaling through toll-like receptors (TLRs), the receptor family recognizing pathogen-associated molecular patterns, is crucial to intestinal epithelial proliferation and mucosal restitution. (mdpi.com)
  • Toll-like receptors (TLRs) have been implicated in the regulation of host responses to microbial Ags. (jimmunol.org)
  • The recent identification of mammalian homologs of the Drosophila gene product dtoll, called Toll-like receptors (TLRs), has revealed a step in the activation of innate immunity and its relationship to adaptive immunity ( 5 ). (jimmunol.org)
  • DCs express a variety of receptors that recognize microbial products, including Toll-like receptors (TLRs), which have been shown to play an important role in pathogen-induced DC activation. (asm.org)
  • Immune cells express multiple Toll-like receptors (TLRs) that are concomitantly activated by a variety of pathogen products. (rupress.org)
  • Toll-like receptors (TLRs) can sense a variety of microbial products, such as microbial membrane lipids or nucleic acids. (rupress.org)
  • Toll-like receptors (TLRs) modulate immune responses and inflammatory diseases, but their role in diabetic nephropathy is not well understood. (asnjournals.org)
  • Toll-like receptors (TLRs) are a conserved family of pattern recognition receptors that play a fundamental role in the innate immune system by triggering proinflammatory signaling pathways in response to microbial pathogens. (asnjournals.org)
  • Accumulating evidence suggests that pattern recognition receptors of the innate immune system such as the toll-like receptors (TLRs) are involved. (umsystem.edu)
  • The innate immune response elicited by activation of TLRs (Toll-like receptors) plays an important role in the pathogenesis of atherosclerosis. (clinsci.org)
  • One key method of recognition is through Toll-like receptors (TLRs), which were first discovered in Drosophila in response to infection with fungal pathogens ( 24 ). (asm.org)
  • Various Toll-like receptors (TLRs) are a part of the innate immune system and involved in cardiac immune response after viral infection. (onlinejacc.org)
  • Toll-liked receptors (TLRs), classified as the damage-associated molecular pattern (DAMP) receptors, have been implicated in the development of several cancers including BCA. (biomedcentral.com)
  • This response is initiated via recognition of pathogen-associated molecular patterns (PAMPS) by pathogen recognition receptors (PRRs) such as the Toll-like receptors (TLRs) (see [ 1 ] for review). (biomedcentral.com)
  • Toll-like receptors (TLRs) modulate the expression of multiple microRNAs (miRNAs). (tcd.ie)
  • Toll-like receptors (TLRs) are evolutionarily conserved family of pattern recognition receptors that play a critical role in regulating both innate and adaptive immune system [ 7 ]. (ijbs.com)
  • Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. (wikipedia.org)
  • TLRs received their name from their similarity to the protein coded by the toll gene identified in Drosophila in 1985 by Christiane Nüsslein-Volhard and Eric Wieschaus. (wikipedia.org)
  • The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of immune receptors called toll-like receptors (TLRs) that are expressed on the membranes of leukocytes including dendritic cells, macrophages, natural killer cells, cells of the adaptive immunity T cells, and B cells, and non-immune cells (epithelial and endothelial cells, and fibroblasts). (wikipedia.org)
  • TLRs are a type of pattern recognition receptor (PRR) and recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). (wikipedia.org)
  • Molecular building blocks of the TLRs are represented in bacteria and in plants, and plant pattern recognition receptors are well known to be required for host defence against infection. (wikipedia.org)
  • Membrane-bound PRRs include Toll like receptors (TLRs) and C-type lectin receptors (CLRs). (wikipedia.org)
  • Recognition of extracellular or endosomal pathogen-associated molecular patterns is mediated by transmembrane proteins known as toll-like receptors (TLRs). (wikipedia.org)
  • Toll like receptor-4 expression in lipopolysaccharide induced lung inflammation. (nih.gov)
  • CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. (uniprot.org)
  • OBJECTIVE We have recently shown that a high-fat high-carbohydrate (HFHC) meal induces an increase in plasma concentrations of endotoxin (lipopolysaccharide [LPS]) and the expression of Toll-like receptor-4 (TLR-4) and suppresser of cytokine signaling-3 (SOCS3) in mononuclear cells (MNCs) in addition to oxidative stress and cellular inflammation. (diabetesjournals.org)
  • Saturated fat and carbohydrates, components of the HFHC meal, known to induce oxidative stress and inflammation, also induce an increase in LPS, TLR-4, and SOCS3. (diabetesjournals.org)
  • RESULTS Indexes of inflammation including nuclear factor-κB (NF-κB) binding, and the expression of SOCS3, tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β in MNCs, increased significantly after glucose and cream intake, but TLR-4 expression and plasma LPS concentrations increased only after cream intake. (diabetesjournals.org)
  • In this context, we wanted to analyze which macronutrient was responsible for the induction of oxidative stress and inflammation, on the one hand, and the increase in LPS concentrations and the expression of TLR-4 and suppresser of cytokine signaling (SOCS)-3 on the other. (diabetesjournals.org)
  • Therefore, pharmacological inhibition of TLR-2/TLR-4 has been a new promising strategy for preventing inflammation in IBD and colorectal cancer. (jimmunol.org)
  • 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)
  • This neurotrophin promotes macrophage recruitment in the mucosa, amplify colonic inflammation and interacts with toll-like receptors (TLR). (bmj.com)
  • We have recently shown that biglycan signaling through TLR 2/4 and the CD14 co-receptor regulates inflammation, suggesting that TLR co-receptors may determine whether biglycan-TLR signaling is pro- or anti-inflammatory. (fraunhofer.de)
  • Interfering with the interaction between biglycan and specific TLR co-receptors could represent a promising therapeutic intervention to curtail kidney inflammation and damage. (fraunhofer.de)
  • Examples of pattern recognition receptors include CD14 and complement receptors ( 3 , 4 ). (jimmunol.org)
  • Expression of Toll-like Receptors 2 and 4 and CD14 during Differentiation of HL-60 Cells Induced by Phorbol 12-Myristate 13-Acetate and 1{alpha}, 25-Dihydroxy-Vitamin D3 -- Li et al. (aacrjournals.org)
  • Additionally, central resistin promotes the activation of the serine kinases Jun NH 2 -terminal kinase and p38 mitogen-activated protein kinase, enhances the serine phosphorylation of insulin receptor substrate-1, and increases the expression of the proinflammatory cytokine interleukin-6 in the hypothalamus and key peripheral insulin-sensitive tissues. (diabetesjournals.org)
  • Toll-like receptors comprise a large family of the pathogen-pattern recognition receptors (PPRR) originally identified in Drosophila in the mid 1990s as a Toll protein ( 1 ). (frontiersin.org)
  • The first human homolog for the Toll protein was described in 1997 ( 3 ). (frontiersin.org)
  • Instead, he and his colleagues found that the proteinases carve up a protein known as fibrinogen, leaving behind fragments that signal through the crucial toll-like receptor 4 to activate the cells of the innate immune system - the macrophages of the airway and airway epithelia. (healthcanal.com)
  • To further investigate Toll-like receptor signaling in vaccinia infection, we first focused on TRIF, the only known adapter protein for TLR3. (pubmedcentralcanada.ca)
  • 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)
  • Aomatsu K, Kato T, Fujita H, Hato F, Oshitani N, Kamata N, Tamura T, Arakawa T, Kitagawa S (2008) Toll-like receptor agonists stimulate human neutrophil migration via activation of mitogen-activated protein kinases. (springer.com)
  • We assessed the impact of monophosphoryl lipid A, a Toll/interleukin-1 receptor-domain-containing adaptor protein inducing interferon-biased Toll-like receptor-4 agonist currently used as a vaccine adjuvant in humans, on post-haemorrhage susceptibility to infection. (inserm.fr)
  • Binding to a Toll-like 4 protein, a pattern recognition receptor that binds bacterial lipopolysaccharide (LPS) to initiate an innate immune response. (zfin.org)
  • Resistin also regulates the synthesis and secretion of key proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-12 in macrophages via a nuclear factor-κB-dependent pathway promoting insulin resistance ( 4 , 6 , 28 , 29 ). (diabetesjournals.org)
  • A naturally occurring TLR-4 antagonist, highly purified lipopolysaccharide (LPS) from Bartonella quintana, was first characterized using mouse macrophages and human dendritic cells (DCs). (nih.gov)
  • Despite its role as a general housekeeping chaperone, gp96 is unexpectedly specific for the Toll family of receptors in macrophages. (rupress.org)
  • T-cell lymphoma research shows that toll like receptor-4 (TLR-4) is highly expressed on CD206+ immunosuppressive macrophages and is implicated in maintaining the tumor microenvironment. (jefferson.edu)
  • They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. (wikipedia.org)
  • Proteins with subgroup 1 TIR domains are receptors for interleukins that are produced by macrophages, monocytes, and dendritic cells and all have extracellular Immunoglobulin (Ig) domains. (wikipedia.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)
  • Peptidoglycan (PGN) from Staphylococcus aureus stimulated mast cells in a TLR2-dependent manner to produce TNF-α, IL-4, IL-5, IL-6, and IL-13, but not IL-1β. (jci.org)
  • Expression of TLR2, -4, and -9 by dendritic cells was assessed on various days postinfection (p.i.) (2, 4, and 6 p.i.) by performing a phenotypic analysis. (asm.org)
  • The expression of Toll-like receptor 2 and 4 (TLR2/4) was detected by flow cytometry and western blot. (ijbs.com)
  • The interaction of TLR2/4 with AGE-LDL was examined by co-immunoprecipitation assay. (ijbs.com)
  • AGE-LDL induced IL-6 and IL-8 production via TLR2/4-MyD88-dependent pathway in tubular epithelial cells. (ijbs.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)
  • Pretreatment with lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 agonist, improves survival to polymicrobial sepsis in neonatal mice by enhancing neutrophil recruitment. (springer.com)
  • OBJECTIVES: Toll-like receptor 4 agonist monosphoryl lipid A has been successfully used as adjuvant in subcutaneous immunotherapy, suggesting reinforcement of allergen-specific tolerance. (ru.nl)
  • Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. (wikipedia.org)
  • Cytoplasmic PRRs include NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). (wikipedia.org)
  • Th17 lymphocytes were required for NEC development, as inhibition of STAT3 or IL-17 receptor signaling attenuated NEC in mice, while IL-17 release impaired enterocyte tight junctions, increased enterocyte apoptosis, and reduced enterocyte proliferation, leading to NEC. (jci.org)
  • TLR 10 is a pseudogene in mice, but is functional in humans ( 4 ). (frontiersin.org)
  • Mice with collagen-induced arthritis (CIA) and mice with spontaneous arthritis caused by interleukin-1 receptor antagonist (IL-1Ra) gene deficiency were treated with TLR-4 antagonist. (nih.gov)
  • Laboratory mice that lacked toll-like receptor 4 did not mount a robust allergic airway disease when challenged by proteinase, viable fungi or other triggers but did have a normal Th2 immunity. (healthcanal.com)
  • C3H/HeJ mice show dysfunction of TLR-4. (arvojournals.org)
  • In contrast, C3H/HeN mice show normal TLR-4 function. (arvojournals.org)
  • Induction of RGC degeneration with TLR-4 ligand was studied with cell viability assay using RGC-5 cells and intravitreal injection of TLR-4 ligand on C3H/HeJ and C3H/HeN mice. (arvojournals.org)
  • Approach and Results- Type 2 diabetic mice with mutated toll-like receptor 4 (DWM) were protected from hyperglycemia and hypertension, despite an increased body weight. (ahajournals.org)
  • The in vivo and in vitro administration of lipopolysaccharide caused endothelial dysfunction in the arteries of wild-type, but not toll-like receptor 4-mutated mice. (ahajournals.org)
  • Additionally, targeting IL-1β with a monoclonal antibody can impede the progression of atherosclerosis in ApoE −/− mice ( 4 ). (spandidos-publications.com)
  • Wire injury of the carotid artery in C57BL/6 wild-type (WT) mice significantly increased intima-to-media ratio in 4 weeks. (ahajournals.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)
  • Bone marrow-derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. (rupress.org)
  • This family of receptors has been characterized for their homology with the Toll receptor of Drosophila that is involved in dorso-ventral patterning during fly development. (biomedcentral.com)
  • Toll-like receptors were first discovered in Drosophila and trigger the synthesis and secretion of cytokines and activation of other host defense programs that are necessary for both innate or adaptive immune responses. (wikipedia.org)
  • One pathway depends on myeloid differentiation marker 88 (MyD88), which elicits proinflammatory responses, whereas the other depends on Toll-IL-1 receptor (TIR) domain-containing adaptor inducing interferon-β (TRIF), which elicits type I interferon production. (sciencemag.org)
  • The differentiation of osteoclasts, cells specialized for bone resorption, is governed by two key factors, macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). (biologists.org)
  • 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)
  • Central resistin treatment inhibited insulin-dependent phosphorylation of insulin receptor (IR), AKT, and extracellular signal-related kinase 1/2 associated with reduced IR expression and with upregulation of suppressor of cytokine signaling-3 and phosphotyrosine phosphatase 1B, two negative regulators of insulin signaling. (diabetesjournals.org)
  • Thrombomodulin promotes diabetic wound healing by regulating toll-like receptor 4 expression. (sigmaaldrich.com)
  • Treatment with TLR-4 antagonist strongly reduced IL-1beta expression in articular chondrocytes and synovial tissue. (nih.gov)
  • In the present study, we demonstrate for the first time that inhibition of TLR-4 suppresses the severity of experimental arthritis and results in lower IL-1 expression in arthritic joints. (nih.gov)
  • The modulation of immune responses by TLR-activated B cells likely results because different TLR agonists induce varying expression patterns of chemokine receptors and molecules crucial for homing, antigen presentation, and formation of the immune synapse ( 17 ⇓ - 19 ). (pnas.org)
  • CONCLUSIONS Although both glucose and cream induce NF-κB binding and an increase in the expression of SOCS3, TNF-α, and IL-1β in MNCs, only cream caused an increase in LPS concentration and TLR-4 expression. (diabetesjournals.org)
  • Our recent work has shown that a high-fat high-cholesterol (HFHC) meal induces oxidative and inflammatory stress in addition to inducing an increase in plasma endotoxin (lipopolysaccharide [LPS]) levels and the expression of Toll-like receptor (TLR)-4, the specific receptor for LPS ( 1 ). (diabetesjournals.org)
  • In addition, our work demonstrated that SOCS3 expression in MNCs is inversely related to the tyrosine phosphorylation of the insulin receptor and directly related to BMI and insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]), consistent with its role in the pathogenesis of insulin resistance. (diabetesjournals.org)
  • The numbers of necrotic and apoptotic cells in the hippocampal CA1 region, the expression levels of TLR-4, NF-κB, cleaved caspase-3, and tumor necrosis factor alpha (TNF-α) in the anterior part of each brain, and the serum levels of TNF-α, interleukin 6 (IL-6), and interleukin 1 beta (IL-1β) were assessed 1 day after ischemia. (mdpi.com)
  • The necrotic cell counts and expression levels of TLR-4, NF-κB, caspase-3, and TNF-α in brain tissue as well as serum levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were significantly higher in the control group than in the other groups. (mdpi.com)
  • In vivo, administration of E5564 1 and 4 hr post‐ischaemia reduced the expression of different pro‐inflammatory chemokines and cytokines, infarct volume, blood-brain barrier breakdown, and improved neuromotor function, an important clinically relevant outcome. (bps.ac.uk)
  • MMP-2, MMP-9 and TLR-4 platelet surface expression as well as PLA formation was examined using flow cytometry. (uni-muenchen.de)
  • The activation of endogenous interleukin-1 receptor-associated kinase in RAW264.7 cells was also inhibited by TAK-242 treatment. (aspetjournals.org)
  • Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4. (nih.gov)
  • 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)
  • Toll-like receptors have also been shown to be an important link between innate and adaptive immunity through their presence in dendritic cells. (wikipedia.org)
  • The purpose of this study was to investigate the role of a common Asp299Gly polymorphism of the TLR-4 gene in atherosclerosis. (biomedsearch.com)
  • Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians. (biomedsearch.com)
  • therefore, the lipopolysaccharide pattern recognition receptor of the host (e.g. (hindawi.com)
  • A variety of cells express proteins called pattern recognition receptors that broadly recognize conserved structures in microorganisms called pathogen-associated molecular patterns (PAMPs) 3 ( 2 ). (jimmunol.org)
  • Toll-like Receptor 4 is a microbe associated molecular pattern receptor well known for it's sensitivity to bacterial lipopolysaccharides (LPS). (reactome.org)
  • The necessity of the pattern recognition receptor, toll-like receptor (TLR)-4, for this innate immune response has been previously shown. (ozgene.com)
  • They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. (wikipedia.org)
  • 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)
  • Degeneration of extracellular matrix of cartilage leads to the production of molecules capable of activating the immune system via Toll-like receptor 4 (TLR-4). (nih.gov)
  • To maximize CD4 + and CD8 + T-cell priming while minimizing regulatory T-cell expansion, DCs need to be fully activated or "licensed" ( 4 ), expressing high levels of costimulatory molecules like CD40, CD80, and CD86 and proinflammatory cytokines like interleukin (IL)-12p70 and IL-6. (aacrjournals.org)
  • Discovering that CD-206 co-localizes with both TLR-4 and EDA indicates that these three molecules interact to help form the tumor microenvironment needed to support keloid formation. (jefferson.edu)
  • Bell JK, Mullen GED, Leifer CA, Mazzoni A, Davies DR et al (2003) Leucine-rich repeats and pathogen recognition in Toll-like receptors. (springer.com)
  • Bacterial and viral products, as well as inflammatory cytokines, induce DC maturation through direct interaction with specific surface receptors ( 15 ). (asm.org)
  • 3,4 Indeed, in obese adipose tissue, the production of proinflammatory and antiinflammatory cytokines is dysregulated, which may play an important role in the development of obesity-related sequelae. (ahajournals.org)
  • Cheng A, Dong Y, Zhu F, Liu Y, Hou FF, Nie J. AGE-LDL Activates Toll Like Receptor 4 Pathway and Promotes Inflammatory Cytokines Production in Renal Tubular Epithelial Cells. (ijbs.com)
  • Toll-like receptors: cellular signal transducers for exogenous molecular patterns causing immune responses. (ebi.ac.uk)
  • These innate immune receptors recognize pathogen-associated molecular patterns (PAMPs) expressed by infectious agents and have a key role in directing the development of an effective immune response against pathogens [ 3 ]. (hindawi.com)
  • However, the resistin receptor and the molecular mechanisms mediating its effects in the hypothalamus, crucial for energy homeostasis control, and key insulin-sensitive tissues are still unknown. (diabetesjournals.org)
  • Alcaide M, Edwards SV (2011) Molecular evolution of the Toll-like receptor multigene family in birds. (springer.com)
  • Interestingly, we also report for the first time, to our knowledge, the direct binding of resistin to Toll-like receptor (TLR) 4 receptors in the hypothalamus, leading to the activation of the associated proinflammatory pathways. (diabetesjournals.org)
  • Activation of microglia, bone marrow-derived macrophage-like cells that function as the resident immune defense system of the brain ( 1 ), is a characteristic feature of most neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, AIDS dementia complex, and amyotrophic lateral sclerosis as well as ischemia and posttraumatic brain injury ( 2 - 4 ). (pnas.org)
  • The objective of this study was to investigate the involvement of TLR-4 activation in the development and progression of autoimmune destructive arthritis. (nih.gov)
  • However, recent reports demonstrate that FFAs directly can stimulate plasma membrane receptors ( 2 , 3 ), suggesting an alternate model in which FFAs cause insulin resistance by stimulating inflammatory pathways through the direct activation of plasma membrane receptors. (diabetesjournals.org)
  • Activation of B cells by Toll-like receptor (TLR) agonists modulates B cell maturation and alters T-cell-dependent B-cell responses to cognate antigen. (pnas.org)
  • Toll-Like Receptor 4 activation and function in diseases: an integrated chemical-biology approach. (europa.eu)
  • The iCD40 receptor permits targeted, reversible activation of CD40 in vivo , potentially bypassing the essential role of CD4 + T cells for activation of DCs. (aacrjournals.org)
  • 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)
  • Ligands and immune cells expressing Toll-Like Receptors. (hindawi.com)
  • The TLR-4 antagonist inhibited DC maturation induced by Escherichia coli LPS and cytokine production induced by both exogenous and endogenous TLR-4 ligands, while having no effect on these parameters by itself. (nih.gov)
  • Assembly of this newly identified heterodimer is regulated by signals from the scavenger receptor CD36, a common receptor for these disparate ligands. (uniprot.org)
  • i.e. , cyclooxygenase 2 (COX-2)-mediated production of prostaglandin E 2 (PGE 2 ), and induction of specific ligands for epidermal growth factor receptor (EGFR). (mdpi.com)
  • The principal function of PGE 2 in this context is to sensitize chemokine receptor 7 (CCR7) to its ligands, CC chemokine ligand 19 (CCL19) and CCL21, thereby enhancing migration to draining lymph nodes ( 7 ). (aacrjournals.org)
  • Toll like receptor-4 (TLR-4) has been indicated in response to various ligands related with cell death signaling, in addition to autoimmune response. (arvojournals.org)
  • Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOFMS) was used to detect TLR-4 ligands after immunoprecipitation with TLR-4 antibody and isolation of retinal membrane proteins at 5 days after ONC. (arvojournals.org)
  • We recently reported that Toll-like receptor 3 (TLR3), which recognizes double-stranded RNA, acts in vaccinia infection in a way that is detrimental to the host. (pubmedcentralcanada.ca)
  • One such passenger is dengue virus (DENV), which infects up to 400 million people each year and comes in several serotypes (1 to 4) and disease presentations-from mild infection to severe disease and sometimes death. (sciencemag.org)
  • Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. (rupress.org)
  • 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)
  • Furthermore, AngII directly regulated toll-like receptor (TLR) mRNA in cell types associated with these diseases. (ahajournals.org)
  • Severe burns can directly or indirectly result in the overgrowth of pathogenic bacteria in the intestines and the disruption of intestinal mechanical barriers, which in turn can trigger the translocation of intestinal bacteria or toxins, leading to systemic inflammatory response syndrome, sepsis and MODS ( 3 , 4 ). (spandidos-publications.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)
  • Biglycan, a small leucine-rich proteoglycan, acts as a danger signal and is classically thought to promote macrophage recruitment via Toll-like receptors (TLR) 2 and 4. (fraunhofer.de)
  • Here, we determined whether the anti-inflammatory effects of sevoflurane postconditioning were mediated via inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway after global transient cerebral ischemia in rats. (mdpi.com)
  • Toll-like receptor 4 inhibition reduces vascular i. (fapesp.br)
  • In a report that appears online in the journal Science , he and colleagues at BCM describe an important component of that chip - a molecule called toll-like receptor 4 that plays a key role in prompting the innate or immediate response that drives allergic disease and asthma. (healthcanal.com)
  • Other work in the field pointed to another immune molecule called toll-like receptor 4 that was believed to play a role in activating T-helper type 2 (Th2) cells. (healthcanal.com)
  • Genetic regulation of this response has been localized to the Lps locus on mouse chromosome 4, through study of the C3H/HeJ and C57BL/10ScCr inbred strains. (rupress.org)
  • 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)
  • Here we show that oxidized LDL and amyloid-beta trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6. (uniprot.org)
  • Is the Subject Area "Immune receptor signaling" applicable to this article? (plos.org)
  • Whereas neither iCD40 nor TLR-4 signaling alone led to high levels of interleukin (IL)-12p70 and IL-6, using iCD40 in combination with lipopolysaccharide (LPS) or monophosphoryl lipid A led to strongly synergistic production of both. (aacrjournals.org)
  • The authors report on the first demonstration that Lycium barbarum polysaccharide (LBP) stimulates tumor necrosis factor-alpha (TNF-α) and IL-1β generation and promotes lymphocyte proliferation in the Toll-like Receptor 4 (TLR 4)/MD2-MAPK signaling pathway. (moleculardevices.com)
  • Here, we sought to identify other co-receptors and characterize their impact on biglycan-TLR signaling. (fraunhofer.de)
  • Toll-like receptor (TLR) signaling triggers cell apoptosis through multiple mechanisms. (biomedcentral.com)
  • Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-κB, all components of the TLR-4 signaling pathway. (rupress.org)
  • Andersen-Nissen E, Smith KD, Bonneau R, Strong RK, Aderem A (2007) A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. (springer.com)
  • Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. (ebi.ac.uk)
  • 7 ) demonstrated in vivo that microglial inducible nitric oxide synthase plays a crucial role in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in the MPTP mouse model of Parkinson's disease. (pnas.org)
  • Treatment of CIA using TLR-4 antagonist substantially suppressed both clinical and histologic characteristics of arthritis without influencing the adaptive anti-type II collagen immunity crucial for this model. (nih.gov)
  • Previous studies have shown that AGE modified albumin initiates inflammatory responses in renal tubular epithelial cells, mainly through interacting with receptor for AGEs (RAGE) [ 4 ]. (ijbs.com)
  • 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)
  • Our findings suggest that the anti-inflammatory actions of sevoflurane postconditioning via inactivation of the TLR-4/NF-κB pathway and subsequent reduction in pro-inflammatory cytokine production, in part, contribute to sevoflurane postconditioning-induced neuroprotection after global transient cerebral ischemia in rats. (mdpi.com)
  • Cellular specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury. (ozgene.com)