*  OC-016 The Toll-like Receptor Pathway Is Recurrently Mutated In Oesophageal Adenocarcinoma | Gut
Results We identified missense mutations in TLR pathway genes in 8/66 (12.1%) of OAC samples, including TLR1 (1.5%), TLR4 (3%), TLR7 (1.5%), TLR9 (3%), MYD88 (1.5%), and TRAF6 (1.5%). TLR9 protein was expressed more highly in Barrett's and OAC than normal oesophageal squamous tissue (p , 0.001). The expression in Barrett's was similar to duodenum, however immunopositivity was increased in OAC (p , 0.05) compared with this control tissue. The staining intensity was generally consistent throughout the Barrett's progression sequence with strong immunopositivity (intensity score 3) in 7.7-14.5% of samples. Within the OAC cohort, there was no significant association between TLR9 expression and any of the clinicopathological variables tested. The only significant difference in survival was observed in a small subset of patients with metastatic disease (N = 14 patients), where median survival was significantly decreased for patients with TLR9 intensity score 2-3 (8 months ± 2.24 (standard error)) ...
  http://gut.bmj.com/content/63/Suppl_1/A8.1
*  Forward genetic analysis of Toll-like receptor responses in wild-derived mice reveals a novel antiinflammatory role for...
Recognition of pathogens by the innate immune system activates Toll-like receptor (TLR)-mediated pathways, resulting in NF-κB-induced transcription of inflammatory cytokines (1). These molecules subsequently direct the initiation of appropriate adaptive responses, leading ultimately to clearance or containment of the invading pathogen (2). Due to their potent biological activity, however, inappropriately prolonged or excessive release of proinflammatory mediators can result in deleterious effects for the host. This is exemplified by the acute-phase cytokine IL-6, whose role in the development of the potentially pathogenic Th17 subset of T cells has recently been described (3). Furthermore, therapies targeting the cytokines IL-1, IL-6, and TNF-α have all shown promising efficacy in the treatment of autoimmune disorders, implying a central role for these molecules in disease pathogenesis (4, 5).. Given the dual nature of proinflammatory cytokines-essential for host defense but ...
  http://jem.rupress.org/content/205/2/305
*  "The role of the toll-like receptor pathway in susceptibility to inflam" by Nigel Crawford 1974
Inflammatory bowel disease (IBD) is a chronic autoimmune disorder that is subdivided into Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC). Epidemiological studies have proven that genetic variation increases susceptibility to IBD, with multiple abnormal genes combined with environmental factors being responsible for disease development. Characterization of these susceptibility genes remains of critical importance to improving understanding of IBD pathogenesis. The overall aim of this study is to discover new IBD susceptibility genes. The initial approach was to study a number of previously described IBD susceptibility loci through characterization of peak LOD score short tandem repeat markers using population- and family-based methods. The IBD1, IBD2, and IBD5 loci were shown to be associated with different forms of IBD in the study cohort. This work formed the basis of the next series of experiments, where the IBD2 locus was mapped in detailed. IBD2 was shown to be
  http://ir.library.louisville.edu/etd/288/
*  Impact of mutations in Toll-like receptor pathway genes on esophageal carcinogenesis - Medicine by Alexandros G.Sfakianakis...
by Daffolyn Rachael Fels Elliott, Juliane Perner, Xiaodun Li, Martyn F. Symmons, Brett Verstak, Matthew Eldridge, Lawrence Bower, Maria O'Donovan, Nick J. Gay, the OCCAMS Consortium , Rebecca C. Fitzgerald Esophageal adenocarcinoma (EAC) develops in an inflammatory microenvironment with reduced microbial diversity, but mechanisms for these influences remain poorly characterized. We hypothesized that mutations targeting…
  https://sfakianakismedblog.wordpress.com/2017/05/22/impact-of-mutations-in-toll-like-receptor-pathway-genes-on-esophageal-carcinogenesis-2/
*  Overexpression of toll-like receptor 4 amplifies the host response to lipopolysaccharide and provides a survival advantage in...
Toll-like receptors are transmembrane proteins that are involved in the innate immune recognition of microbial constituents. Among them, Toll-like receptor 4 (Tlr4) is a crucial signal transducer for LPS, the major component of Gram-negative bacteria outer cell membrane. The contribution of Tlr4 to the host response to LPS and to infection with virulent Salmonella typhimurium was studied in four transgenic (Tg) strains including three overexpressing Tlr4. There was a good correlation between the level of Tlr4 mRNA expression and the sensitivity to LPS both in vitro and in vivo: Tg mice possessing the highest number of Tlr4 copies respond the most to LPS. Overexpression of Tlr4 by itself appears to have a survival advantage in Tg mice early during infection: animals possessing more than two copies of the gene survived longer and in a greater percentage to Salmonella infection. The beneficial effect of Tlr4 overexpression is greatly enhanced ...
  http://eprints.lancs.ac.uk/86171/
*  TLR 1 - Wikipedia
TLR 1 is a member of the toll-like receptor family (TLR) of pattern recognition receptors of the innate immune system. TLR1 recognizes pathogen-associated molecular pattern with a specificity for gram-positive bacteria. TLR1 has also been designated as CD281 (cluster of differentiation 281). TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is ubiquitously expressed, and at higher levels than other TLR genes. Different length transcripts presumably resulting from use of alternative polyadenylation site, and/or from alternative splicing, have been noted for this gene. TLR1 recognises peptidoglycan and (triacyl) lipoproteins in concert with TLR2 (as ...
  https://en.wikipedia.org/wiki/TLR_1
*  Signaling by Toll-Like Receptors | Science Books
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 ...
  http://sciencebookss.blogspot.com/2008/12/signaling-by-toll-like-receptors.html
*  Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance, and Insulin...
Recent studies have demonstrated subset-specific roles for B cells in both aggravating and regulating the perturbations associated with obesity. Winer et al4 demonstrated that B-2 B cells promote insulin resistance and glucose intolerance through production of pathogenic antibodies. Additional studies have shown that sorted splenic B-2 B cells from obese mice secrete more IL-6 and MIP-2 and less IL-10 compared with lean controls,48 and circulating B cells (of which the vast majority are B-2) from patients with type 2 diabetes mellitus are also skewed toward a proinflammatory phenotype after toll-like receptor stimulation.49 Our adoptive transfers of B-2 B cells provide further evidence that B-2 B cells promote metabolic dysfunction during DIO. In contrast, B-1a B cells were recently shown to protect against the inflammatory and metabolic consequences of DIO through a combination of IgM and IL-10 production,50 and B-cell-derived IL-10 reduces adipose tissue ...
  http://atvb.ahajournals.org/content/36/4/682
*  KEGG PATHWAY: Toll-like receptor signaling pathway - Homo sapiens (human)
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 ...
  http://www.genome.jp/kegg-bin/show_pathway?hsa04620+5293
*  KEGG PATHWAY: Toll-like receptor signaling pathway - Homo sapiens (human)
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 ...
  http://www.genome.jp/kegg-bin/show_pathway?hsa04620+56480
*  KEGG PATHWAY: Toll-like receptor signaling pathway - Homo sapiens (human)
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 ...
  http://www.genome.jp/kegg-bin/show_pathway?hsa04620+6416
*  KEGG PATHWAY: Toll-like receptor signaling pathway - Mus musculus (mouse)
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 ...
  http://www.genome.jp/kegg-bin/show_pathway?mmu04620
*  Lipocortin 1 - PI3K Signaling in B and T Lymphocytes
We evaluated Toll-like receptor (TLR) function in primary human dendritic cells from 104 young (age 21C30) and older ( 65 years) individuals. dysregulation of cytokine production that may limit further activation by TLR engagement. Our results provide evidence for immunosenescence in dendritic cells; notably, defects in cytokine production were strongly associated with poor antibody response to influenza immunization, a functional consequence of impaired TLR function in the aging innate immune response. Introduction Aging is associated with a progressive decline in immune function (immunosenescence) resulting in increased susceptibility to viral and bacterial infections and decreased response to vaccines (1C3). Age-associated perturbations in the humoral and cell-mediated arms of the adaptive immune system are well documented (3, 4); however, the impact of aging on the innate immune system is less well defined. Age related deficiencies of the innate immune system are ...
  http://health-e-nc.org/category/lipocortin-1/
*  toll-like receptor signaling pathway QuickView - Correlation Engine
Any series of molecular signals generated as a consequence of binding to a toll-like receptor. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate innate immune response.
  http://www.nextbio.com/b/search/ov/toll-like%20receptor%20signaling%20pathway?id=31713&type=biogroup
*  Http://query.nytimes.com/gst/fullpage.html?res=9e0ce5d81130f936
Toll-like receptors are part of the innate immune system, which is the body's first line of defense against pathogens. The innate system's job is to keep pathogens in check for a few days until the second-line defense, the adaptive immune system, can kick in. The adaptive immune system marshals antibodies and T cells that are highly specific for a particular pathogen. Once created, the antibodies and T cells can make quick work of the same pathogen if it appears even years later -- the reason that vaccines work and that people do not get chickenpox or measles more than once. For many years most immunologists had paid scant attention to the innate immune system, considering it far more primitive than the adaptive system. But now scientists realize that the toll-like receptors in the innate system are necessary for activating the adaptive system. ''The adaptive immune system would not even know what hit it, ...
  http://healthdrugpdf.com/l/labs.mmg.pitt.edu1.html
*  Frontiers | Fungal pathogens-a sweet and sour treat for toll-like receptors | Frontiers in Cellular and Infection Microbiology
Hundred-thousands of fungal species are present in our environment, including normal colonizers that constitute part of the human microbiota. The homeostasis of host-fungus interactions encompasses efficient fungal sensing, tolerance at mucosal surfaces, as well as antifungal defenses. Decrease in host immune fitness or increase in fungal burden may favor pathologies, ranging from superficial mucocutaneous diseases to invasive life-threatening fungal infections. Toll-like receptors (TLRs) are essential players in this balance, due to their ability to control both inflammatory and anti-inflammatory processes upon recognition of fungal-specific pathogen-associated molecular patterns (PAMPs). Certain members of the TLR family participate to the initial recognition of fungal PAMPs on the cell surface, as well as inside phagosomes of innate immune cells. Active signaling cascades in phagocytes ultimately enable fungus clearance and the release of cytokines that shape and instruct ...
  http://journal.frontiersin.org/article/10.3389/fcimb.2012.00142/full
*  Advances in Toll-like receptor biology: Modes of activation by diverse stimuli. - Nuffield Department of Orthopaedics,...
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 ...
  https://www.ndorms.ox.ac.uk/publications/578816
*  Review: The importance of toll-like receptors in the bovine innate immune system
Review on the importance of toll-like receptors in the bovine innate immune system, the bovine TLR family and current knowledge about signaling mechanisms
  https://www.bio-rad-antibodies.com/cow-bovine-toll-like-receptors-review.html
*  Acetylation of MKP-1 and the Control of Inflammation | Science Signaling
Innate immune responses mediated by Toll-like receptors (TLRs), a class of pattern-recognition receptors, play a critical role in the defense against microbial pathogens. However, excessive TLR-mediated responses result in sepsis, autoimmunity, and chronic inflammation. To prevent deleterious activation of TLRs, cells have evolved multiple mechanisms that inhibit innate immune reactions. Stimulation of TLRs induces the expression of the gene encoding the mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a nuclear-localized dual-specificity phosphatase that preferentially dephosphorylates p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in the attenuation of TLR-triggered production of proinflammatory cytokines. MKP-1 is posttranslationally modified by multiple mechanisms, including phosphorylation. A study now demonstrates that MKP-1 is also acetylated on a key lysine residue following stimulation of TLRs. Acetylation of MKP-1 promotes the ...
  http://stke.sciencemag.org/content/1/41/pe44
*  British Library EThOS: Development of a phosphoproteomic screen of innate immune signalling : identification and...
Toll-like receptors (TLRs) expressed by antigen-presenting cells of the innate immune system, such as macrophages, detect microbial products and activate signalling cascades that initiate specific gene expression programmes that define the subsequent adaptive immune response. However, it is poorly understood how TLR-specific responses arise, as many of the signalling components are common to multiple TLRs, and it is likely that as yet undiscovered phosphorylations of signalling proteins contribute to specificity of TLR pathways. TLR4, the receptor for lipopolysaccharide (LPS), is used as a model system for TLR signalling, as it activates many of the signalling mechanisms utilised by other TLRs, and I attempted to discover novel regulatory phosphorylations in LPS-activated RAW 264.7 macrophages. Because it is not yet possible to accurately predict post-translational modifications from genomic data, the exact sites of phosphorylation have to be identified ...
  http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526343
*  Leading cause of death in 'preemies' might be controlled by resetting a molecu... ( Washington D.C. -- Blocking signal...)
...Washington D.C. -- Blocking signals from a key molecular receptor t...David J. Hackam and his laboratory team at the Childrens Hospital of P...Toll-like receptors are key players in the innate immune system. Protr...But Hackams group found that the stresses of oxygen deprivation and bo...,Leading,cause,of,death,in,'preemies',might,be,controlled,by,resetting,a,molecular,switch,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
  http://www.bio-medicine.org/biology-news-1/Leading-cause-of-death-in-preemies-might-be-controlled-by-resetting-a-molecular-switch-1409-1/
*  ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes.
Toll-like receptors (TLRs) are sentinels of the host defense system, which recognize a large number of microbial pathogens. The host defense system may be inefficient or inflammatory diseases may develop if microbial recognition by TLRs and subsequen
  http://www.biomedsearch.com/nih/ATF4-directly-recruited-by-TLR4/23241898.html
*  Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne - pdf download
Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne. . Download books free in pdf. Online library with books, university works and thousands of documents available to read online and download.
  http://books.duhnnae.com/2017/aug2/150174214789-Toll-like-receptor-2-activation-and-comedogenesis-implications-for-the-pathogenesis-of-acne.php