Tlr4

Summary

Gene Symbol: Tlr4
Description: toll-like receptor 4
Alias: Lps, Ly87, Ran/M1, Rasl2-8, toll-like receptor 4, Toll like receptor 4, lipopolysaccharide response
Species: mouse

Top Publications

  1. ncbi Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene
    A Poltorak
    Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235 9050, USA
    Science 282:2085-8. 1998
  2. ncbi Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis
    Seth Rakoff-Nahoum
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 118:229-41. 2004
  3. ncbi Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product
    K Hoshino
    Department of Biochemistry, Hyogo College of Medicine, Japan
    J Immunol 162:3749-52. 1999
  4. pmc Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits
    Sung Chun Tang
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 104:13798-803. 2007
  5. pmc Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway
    Seija Lehnardt
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:8514-9. 2003
  6. ncbi Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response
    Sara W Montminy
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nat Immunol 7:1066-73. 2006
  7. ncbi Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Osaka, Japan
    J Immunol 165:5392-6. 2000
  8. ncbi Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran
    Ho Min Kim
    Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejon, Korea 305 701
    Cell 130:906-17. 2007
  9. ncbi Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nature 420:324-9. 2002
  10. pmc Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4)
    S T Qureshi
    Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4
    J Exp Med 189:615-25. 1999

Research Grants

Detail Information

Publications232 found, 100 shown here

  1. ncbi Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene
    A Poltorak
    Howard Hughes Medical Institute and the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235 9050, USA
    Science 282:2085-8. 1998
    ..of C3H/HeJ mice was shown to correspond to a missense mutation in the third exon of the Toll-like receptor-4 gene (Tlr4), predicted to replace proline with histidine at position 712 of the polypeptide chain...
  2. ncbi Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis
    Seth Rakoff-Nahoum
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 118:229-41. 2004
    ..These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions...
  3. ncbi Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product
    K Hoshino
    Department of Biochemistry, Hyogo College of Medicine, Japan
    J Immunol 162:3749-52. 1999
    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...
  4. pmc Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits
    Sung Chun Tang
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 104:13798-803. 2007
    ..Our findings establish a proapoptotic signaling pathway for TLR2 and -4 in neurons that may render them vulnerable to ischemic death...
  5. pmc Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway
    Seija Lehnardt
    Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:8514-9. 2003
    ..We show that in the CNS, specific activation of innate immunity through a Toll-like receptor 4 (TLR4)-dependent pathway leads to neurodegeneration...
  6. ncbi Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response
    Sara W Montminy
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nat Immunol 7:1066-73. 2006
    ..the plague bacillus Yersinia pestis synthesizes lipopolysaccharide (LPS)-lipid A with poor Toll-like receptor 4 (TLR4)-stimulating activity. To address the effect of weak TLR4 stimulation on virulence, we modified Y...
  7. ncbi Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Osaka, Japan
    J Immunol 165:5392-6. 2000
    ..We previously showed that TLR2 recognizes Gram-positive bacterial components whereas TLR4 recognizes LPS, a component of Gram-negative bacteria...
  8. ncbi Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran
    Ho Min Kim
    Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejon, Korea 305 701
    Cell 130:906-17. 2007
    b>TLR4 and MD-2 form a heterodimer that recognizes LPS (lipopolysaccharide) from Gram-negative bacteria. Eritoran is an analog of LPS that antagonizes its activity by binding to the TLR4-MD-2 complex...
  9. ncbi Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nature 420:324-9. 2002
    ..Another adaptor, TIRAP (also known as Mal), has been cloned as a molecule that specifically associates with TLR4 and thus may be responsible for the MyD88-independent response...
  10. pmc Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4)
    S T Qureshi
    Department of Medicine, McGill University, Montreal, Quebec, Canada H3G 1A4
    J Exp Med 189:615-25. 1999
    ..7 Mb. 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...
  11. pmc Toll-like receptor 4 contributes to efficient control of infection with the protozoan parasite Leishmania major
    Pascale Kropf
    Faculty of Medicine, Department of Immunology, Imperial College London, London, United Kingdom
    Infect Immun 72:1920-8. 2004
    ..Our results show that TLR4 contributes to the control of parasite growth in both phases of the immune response...
  12. pmc The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 201:1135-43. 2005
    ..Toll-like receptor 4 (TLR4)-defective (C3H/Hej) mice exhibited less damage in the hepatic I/R model than did wild-type (C3H/HeOuj) mice...
  13. ncbi Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components
    O Takeuchi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Japan
    Immunity 11:443-51. 1999
    Toll-like receptor (TLR) 2 and TLR4 are implicated in the recognition of various bacterial cell wall components, such as lipopolysaccharide (LPS). To investigate in vivo roles of TLR2, we generated TLR2-deficient mice...
  14. ncbi TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Nat Immunol 4:1144-50. 2003
    ..for proinflammatory cytokine production, whereas TRIF mediates the MyD88-independent pathway from TLR3 and TLR4. Here we have identified a fourth TIR domain-containing adaptor, TRIF-related adaptor molecule (TRAM), and analyzed ..
  15. ncbi Regulation of lung injury and repair by Toll-like receptors and hyaluronan
    Dianhua Jiang
    Department of Medicine, Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA
    Nat Med 11:1173-9. 2005
    ..fragments isolated from serum of individuals with acute lung injury stimulated macrophage chemokine production in a TLR4- and TLR2-dependent manner...
  16. ncbi Toll-like receptors modulate adult hippocampal neurogenesis
    Asya Rolls
    Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nat Cell Biol 9:1081-8. 2007
    ..We show that TLR2 and TLR4 are found on adult neural stem/progenitor cells (NPCs) and have distinct and opposing functions in NPC ..
  17. pmc Toll-like receptor 4 promotes α-synuclein clearance and survival of nigral dopaminergic neurons
    Nadia Stefanova
    Division of Clinical Neurobiology, Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
    Am J Pathol 179:954-63. 2011
    ..The aim of this study was to define the role of TLR4 in α-synuclein-linked neurodegeneration...
  18. ncbi The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo
    Silvia Bellocchio
    Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    J Immunol 172:3059-69. 2004
    ..MyD88 adapter may occur through signaling by distinct members of the IL-1R/TLR superfamily, including IL-1R, TLR2, TLR4, and TLR9, with the proportional role of the individual receptors varying depending on fungal species, fungal ..
  19. pmc Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105
    Senad Divanovic
    Division of Molecular Immunology, Cincinnati Children s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Nat Immunol 6:571-8. 2005
    ..We report here that RP105 expression was wide, directly mirroring that of TLR4 on antigen-presenting cells...
  20. pmc Toll-like receptor 2 controls expansion and function of regulatory T cells
    Roger P M Sutmuller
    Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    J Clin Invest 116:485-94. 2006
    ..Here, we report that the TLR2 ligand Pam3Cys, but not LPS (TLR4) or CpG (TLR9), directly acts on purified Tregs in a MyD88-dependent fashion...
  21. doi Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury
    Yumiko Imai
    IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohrgasse 3, A 1030 Vienna, Austria
    Cell 133:235-49. 2008
    ..Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI)...
  22. pmc Role of Toll-like receptor 4 in induction of cell-mediated immunity and resistance to Brucella abortus infection in mice
    Marco A Campos
    Department of Biochemistry and Immunology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil
    Infect Immun 72:176-86. 2004
    ..CHO reporter cell lines transfected with CD14 and TLRs showed that B. abortus triggers both TLR2 and TLR4. In contrast, lipopolysaccharide (LPS) and lipid A derived from Brucella rough (R) and smooth (S) strains activate ..
  23. ncbi Control of B-cell responses by Toll-like receptors
    Chandrashekhar Pasare
    Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, 300 Cedar Street New Haven, Connecticut 06510, USA
    Nature 438:364-8. 2005
    ..We find that, in addition to CD4+ T-cell help, generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells...
  24. ncbi Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient mice
    Can Xiang Cao
    Department of Neurology, Daping Hospital, The Third Military Medical University, ChangJiang Branch Road 10, Daping, Yuzhong District, Chongqing 400042, China
    Biochem Biophys Res Commun 353:509-14. 2007
    ..Our study aims to explore the function of Toll-like receptor 4 (TLR4) in the process of cerebral ischemia-reperfusion...
  25. pmc Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4
    Markus M Heimesaat
    Institut für Mikrobiologie und Hygiene, Charite Universitatsmedizin Berlin, Charite Campus Mitte, Berlin, Germany
    PLoS ONE 2:e662. 2007
    ..We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR) signaling...
  26. pmc Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4
    Richard P Darveau
    Department of Periodontics, University of Washington, Health Sciences Center, Box 357444, Seattle, WA 98195, USA
    Infect Immun 72:5041-51. 2004
    ..have reported that it can be an agonist for Toll-like receptor 2 (TLR2) as well as an antagonist or agonist for TLR4. In this report it is shown that P...
  27. pmc Chitin induces accumulation in tissue of innate immune cells associated with allergy
    Tiffany A Reese
    Howard Hughes Medical Institute, Departments of Medicine and Microbiology Immunology, University of California San Francisco, San Francisco, California 94143 0795, USA
    Nature 447:92-6. 2007
    ..Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase...
  28. ncbi Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity
    Francis Kim
    Department of Medicine, University of Washington, Seattle, WA 98104, USA
    Circ Res 100:1589-96. 2007
    ..are activated in the vasculature of mice with diet-induced obesity, and if so, whether Toll-Like Receptor-4 (TLR4), a key mediator of innate immunity, contributes to these responses...
  29. ncbi Gene-specific control of inflammation by TLR-induced chromatin modifications
    Simmie L Foster
    Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06405, USA
    Nature 447:972-8. 2007
    ..These findings illustrate an adaptive response in macrophages and reveal component-specific regulation of inflammation...
  30. doi TLR-4 deficiency protects against focal cerebral ischemia and axotomy-induced neurodegeneration
    Ulkan Kilic
    Department of Neurology, University Hospital Zurich, Frauenklinikstr 26, CH 8091 Zurich, Switzerland
    Neurobiol Dis 31:33-40. 2008
    ..Our data indicate that innate immunity may represent an attractive target for neuroprotective treatments in stroke and neurodegeneration...
  31. pmc Reciprocal expression and signaling of TLR4 and TLR9 in the pathogenesis and treatment of necrotizing enterocolitis
    Steven C Gribar
    Department of Surgery, Division of Pediatric Surgery, Children s Hospital of Pittsburgh, and University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    J Immunol 182:636-46. 2009
    ..We now demonstrate that the developing mouse intestine shows reciprocal patterns of expression of TLR4 and TLR9, the receptor for bacterial DNA (CpG-DNA)...
  32. pmc Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edema
    Giorgio Zanotti
    Division of Cardiothoracic Surgery, Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7065, USA
    Am J Physiol Lung Cell Mol Physiol 297:L52-63. 2009
    ..We employed a murine model of hilar clamping (1 h) with reperfusion times between 15 min and 3 h in TLR4-sufficient (C3H/OuJ) and TLR4-deficient (C3H/HeJ) anesthetized mice with additional studies in chimeric and myeloid ..
  33. ncbi Toll-like receptor 4-mediated apoptosis of pancreatic cells in cerulein-induced acute pancreatitis in mice
    Si Qin Ding
    Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
    Hepatobiliary Pancreat Dis Int 9:645-50. 2010
    Toll-like receptor 4 (TLR4) plays an important role in the occurrence and development of acute pancreatitis (AP). Apoptosis of pancreatic cells is closely related to the severity of AP...
  34. pmc TLR4 promotes Cryptosporidium parvum clearance in a mouse model of biliary cryptosporidiosis
    STEVEN P O'HARA
    Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, and Mayo Clinic Center for Cell Signaling, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Parasitol 97:813-21. 2011
    ..In previous work, we demonstrated that TLR4, which is activated by gram-negative lipopolysaccharide (LPS), is upregulated in cholangiocytes in response to ..
  35. pmc Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway
    Sudan He
    Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital, Soochow University, Suzhou 215123, China
    Proc Natl Acad Sci U S A 108:20054-9. 2011
    ..IFN-β (TRIF/TICAM-1), which is dispensable for TNF-α-induced necrosis, forms a complex with RIP3 upon TLR3/TLR4 activation and is essential for TLR3/TLR4-induced necrosis...
  36. pmc Inhibition of TLR4 signaling prolongs Treg-dependent murine islet allograft survival
    N Zhang
    Immunobiology Center, Department of Gene and Cell Medicine, Mount Sinai School of Medicine, NY 10029 6574, USA
    Immunol Lett 127:119-25. 2010
    ..We hypothesized that the recognition of endogenous TLR4 ligands is occurring at the time of transplantation, and these innate signals drive the inflammation and affect ..
  37. pmc Role of Toll-like receptors 2 and 4 in pulmonary inflammation and injury induced by pneumolysin in mice
    Mark C Dessing
    Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    PLoS ONE 4:e7993. 2009
    ..The primary objective of the present study was to determine the role of TLR2 and TLR4 in lung inflammation induced by intrapulmonary delivery of PLN.
  38. ncbi Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex
    K Ohashi
    German Diabetes Research Institute, Heinrich Heine University, Dusseldorf, Germany
    J Immunol 164:558-61. 2000
    ..Both the induction of TNF-alpha and NO formation were found dependent on a functional Tlr4 whereas stimulation of macrophages by CpG DNA was Tlr4 independent. We conclude that Tlr4 mediates hsp60 signaling...
  39. ncbi Candida albicans phospholipomannan is sensed through toll-like receptors
    Thierry Jouault
    Laboratoire de Mycologie Fondamentale et Appliquée, Inserm EMI0360, Universite de Lille II, Lille, France
    J Infect Dis 188:165-72. 2003
    ..with wild-type cells, which produced large amounts of TNF-alpha after incubation with PLM, the deletion of the TLR4 and TLR6 genes led to a limited alteration of the PLM-induced response...
  40. ncbi Toll-like receptor 4 mediates mitochondrial DNA damage and biogenic responses after heat-inactivated E. coli
    Hagir B Suliman
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    FASEB J 19:1531-3. 2005
    ..In wild-type (Wt) mice injected with heat-inactivated E. coli, hepatic TLR4 and TLR2 proteins were up-regulated with TLR-dependent increases in transcript levels for tumor necrosis factor (..
  41. ncbi TLRs regulate the gatekeeping functions of the intestinal follicle-associated epithelium
    Sophie Chabot
    Department of Pediatrics, Harvard Medical School, GI Cell Biology Laboratory, Children s Hospital Boston and Harvard Digestive Diseases Center, Boston, MA 02115, USA
    J Immunol 176:4275-83. 2006
    ..migration of subepithelial DCs into the FAE, but not into villus epithelium of wild-type and TLR4-deficient mice. These responses were not observed in TLR2-deficient mice...
  42. pmc NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1
    Sinead M Miggin
    School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
    Proc Natl Acad Sci U S A 104:3372-7. 2007
    ..However, we found that Mal was cleaved by caspase-1 and that inhibition of caspase-1 activity blocked TLR2- and TLR4-mediated NF-kappaB and p38 MAP kinase activation but not IL-1 or TLR7 signaling, which are Mal independent...
  43. ncbi Systemic inflammation and end organ damage following trauma involves functional TLR4 signaling in both bone marrow-derived cells and parenchymal cells
    Kevin P Mollen
    Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15217, USA
    J Leukoc Biol 83:80-8. 2008
    ..b>TLR4, in particular, plays a key role in systemic and remote organ responses to hemorrhagic shock (HS) and peripheral ..
  44. pmc Rab5 activation by Toll-like receptor 2 is required for Trypanosoma cruzi internalization and replication in macrophages
    Elena Maganto-Garcia
    Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
    Traffic 9:1299-315. 2008
    ..Moreover, using macrophages from knockout mice, we found that activation of Rab5, fusion of early endosomes and phagocytosis induced by T. cruzi infection involved Toll-like receptor (TLR)2 but were independent of TLR4 receptors.
  45. pmc Toll-like receptor 4 restricts retinal progenitor cell proliferation
    Ravid Shechter
    Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel
    J Cell Biol 183:393-400. 2008
    ..In this study, we show that in the mammalian eye, the function of Toll-like receptor 4 (TLR4) extends beyond regulation of the innate immune response; it restricts RPC proliferation...
  46. pmc Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides
    Per Björk
    Active Biotech AB, Lund, Sweden
    PLoS Biol 7:e97. 2009
    ..end products (RAGE) and also an endogenous Toll ligand in that it shows a highly specific interaction with TLR4/MD2. Both these interactions are inhibited by quinoline-3-carboxamides...
  47. pmc Protein kinase D1 is essential for MyD88-dependent TLR signaling pathway
    Jeoung Eun Park
    Department of Pediatrics, Children s Foundation Research Center, Le Bonheur Children s Medical Center, University of Tennessee Health Science Center, Memphis, TN 38103, USA
    J Immunol 182:6316-27. 2009
    ..but is not involved in expression of type I IFNs induced by TLR ligands and TRIF-dependent genes induced by TLR3 and TLR4 ligands. These results demonstrate that PKD1 is essential for MyD88-dependent proinflammatory immune responses.
  48. pmc Mice that exclusively express TLR4 on endothelial cells can efficiently clear a lethal systemic Gram-negative bacterial infection
    Graciela Andonegui
    Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Clin Invest 119:1921-30. 2009
    Recognition of LPS by TLR4 on immune sentinel cells such as macrophages is thought to be key to the recruitment of neutrophils to sites of infection with Gram-negative bacteria...
  49. pmc Pseudomonas aeruginosa LPS or flagellin are sufficient to activate TLR-dependent signaling in murine alveolar macrophages and airway epithelial cells
    Eloïse Raoust
    Unité de Défense Innée et Inflammation, Institut Pasteur, Paris, France
    PLoS ONE 4:e7259. 2009
    ..Based on whole animal experiments, using TLR knockout mice, the control of this bacterium is believed to occur by the recognition of LPS and flagellin by TLRs 2,4 and 5, respectively.
  50. pmc Hematopoietic cell-specific deletion of toll-like receptor 4 ameliorates hepatic and adipose tissue insulin resistance in high-fat-fed mice
    Maziyar Saberi
    Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, CA 92093, USA
    Cell Metab 10:419-29. 2009
    ..The Toll-like receptor 4 (Tlr4) is a key initiator of inflammatory responses in macrophages...
  51. pmc Peroxisome proliferator-activated receptor gamma negatively regulates IFN-beta production in Toll-like receptor (TLR) 3- and TLR4-stimulated macrophages by preventing interferon regulatory factor 3 binding to the IFN-beta promoter
    Wei Zhao
    Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Immunology, Shandong University Medical School, Jinan, Shandong 250012, China
    J Biol Chem 286:5519-28. 2011
    ..analyzed the effect of the PPAR-γ agonists on IFN-β production in peritoneal primary macrophages in response to LPS and poly(I:C). PPAR-γ agonists inhibited LPS and poly(I:C)-induced IFN-β transcription and secretion...
  52. ncbi A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways
    M T Audrey Nguyen
    Division of Endocrinology Metabolism, University of California, San Diego, La Jolla, California 92093, USA
    J Biol Chem 282:35279-92. 2007
    ..7 cells primarily via the JNK signaling cascade and that TLR2 and TLR4 are upstream of JNK and help transduce FFA proinflammatory signals...
  53. pmc Campylobacter jejuni-induced activation of dendritic cells involves cooperative signaling through Toll-like receptor 4 (TLR4)-MyD88 and TLR4-TRIF axes
    Vijay A K Rathinam
    Comparative Enteric Diseases Laboratory, National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA
    Infect Immun 77:2499-507. 2009
    ..In this study, we investigated the role of TLR2, TLR4, MyD88, and TRIF signaling in C. jejuni-induced inflammatory activation of DCs...
  54. pmc Stimulator of IFN gene is critical for induction of IFN-beta during Chlamydia muridarum infection
    Daniel Prantner
    Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Immunol 184:2551-60. 2010
    ..Previous studies have demonstrated no role for TLR4 and a partial role for MyD88 in chlamydial-induced IFN-beta...
  55. pmc Exacerbation of murine ileitis by Toll-like receptor 4 mediated sensing of lipopolysaccharide from commensal Escherichia coli
    M M Heimesaat
    Institut für Mikrobiologie und Hygiene, Charite, Universitatsmedizin Berlin, Campus Charite Mitte, Dorotheenstr 96, D 10117 Berlin, Germany
    Gut 56:941-8. 2007
    ..In the course of inflammatory bowel diseases (IBD) and acute murine ileitis following peroral Toxoplasma gondii infection, commensal Escherichia coli accumulate at inflamed mucosal sites and aggravate small intestinal immunopathology...
  56. ncbi Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1-TLR4 signaling
    Jie Fan
    Department of Surgery, School of Medicine, University of Pittsburgh, and Division of Pediatric Surgery, Children s Hospital of Pittsburgh, PA 15213, USA
    J Immunol 178:6573-80. 2007
    ..PMN NAD(P)H oxidase has been thought to be an important source of ROS following HS/R. TLR4 sits at the interface of microbial and sterile inflammation by mediating responses to both bacterial endotoxin and ..
  57. pmc Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen
    Stephanie C Eisenbarth
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Exp Med 196:1645-51. 2002
    ..Here, we report that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization...
  58. pmc House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells
    Hamida Hammad
    Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Medicine, Ghent University, Ghent, Belgium
    Nat Med 15:410-6. 2009
    ..We show in irradiated chimeric mice that Toll-like receptor 4 (TLR4) expression on radioresistant lung structural cells, but not on DCs, is necessary and sufficient for DC activation ..
  59. ncbi Endotoxin induced uveitis in the mouse: susceptibility and genetic control
    Q Li
    Laboratory of Immunology and Clinical Branch, NEI, NIH, Bethesda, MD 20892 1858, USA
    Exp Eye Res 61:629-32. 1995
    ..We studied ten strains with differing major histocompatibility-2 genes, lipopolysaccharide response gene, and strains with mast cell depletion and its sham control...
  60. ncbi Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states
    Geoffrey M Gersuk
    Fred Hutchinson Cancer Research Center, University of Washington, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    J Immunol 176:3717-24. 2006
    ..These data demonstrate one mechanism by which the pulmonary inflammatory response is tailored toward metabolically active cells, thereby avoiding unnecessary tissue damage with frequent inhalation of ubiquitous spores...
  61. ncbi Differential involvement of TLR2 and TLR4 in host survival during pulmonary infection with Chlamydia pneumoniae
    Nuria Rodriguez
    Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany
    Eur J Immunol 36:1145-55. 2006
    The relevance of TLR2 and TLR4 for recognizing Chlamydia pneumoniae in vivo during pulmonary infection and to survive the infection was explored. We found that early immune responses triggered by C...
  62. ncbi Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
    Jane Tian
    Inflammation and Autoimmune Group, Research Department, MedImmune, Gaithersburg, Maryland 20878, USA
    Nat Immunol 8:487-96. 2007
    ..Our data demonstrate a mechanism by which HMGB1 and RAGE activate plasmacytoid dendritic cells and B cells in response to DNA and contribute to autoimmune pathogenesis...
  63. ncbi Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids
    Christophe Paget
    Institut National de la Recherche Médicale, U547, 59019 Lille, France
    Immunity 27:597-609. 2007
    ..Together with the lipopolysaccharide-detecting receptor TLR4, activation of the nucleic acid sensors TLR7 and TLR9 in DCs were particularly potent in stimulating iNKT cells to ..
  64. pmc Cutting edge: bacterial infection induces hematopoietic stem and progenitor cell expansion in the absence of TLR signaling
    Philip O Scumpia
    Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610 0286, USA
    J Immunol 184:2247-51. 2010
    ..In this study, we report that endotoxin treatment in vivo induces TLR4, MyD88, and Toll/IL-1 resistance domain-containing adaptor-inducing IFN-beta (TRIF)-dependent expansion of BM HSPCs...
  65. ncbi Limited contribution of Toll-like receptor 2 and 4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans
    Kiwamu Nakamura
    Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan
    FEMS Immunol Med Microbiol 47:148-54. 2006
    The present study was designed to elucidate the role of Toll-like receptor (TLR) 2 and TLR4 in the host response to Cryptococcus neoformans...
  66. ncbi Innate immune response to Francisella tularensis is mediated by TLR2 and caspase-1 activation
    Hanfen Li
    Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    J Leukoc Biol 80:766-73. 2006
    ..and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein. F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers...
  67. pmc Both TLR2 and TLR4 are required for the effective immune response in Staphylococcus aureus-induced experimental murine brain abscess
    Werner Stenzel
    Department of Neuropathology, University of Cologne, Joseph Stelzmann Strasse 9, D 50931 Köln, Germany
    Am J Pathol 172:132-45. 2008
    ..Lipoproteins and lipopolysaccharides are specifically recognized by TLR2 and TLR4, respectively. We examined the in vivo role of TLR2 and TLR4 in Staphylococcus aureus-induced brain abscess...
  68. ncbi Lipoteichoic acid-induced lung inflammation depends on TLR2 and the concerted action of TLR4 and the platelet-activating factor receptor
    Sylvia Knapp
    Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    J Immunol 180:3478-84. 2008
    ..Using mice deficient for LBP, CD14, TLR2, TLR4, or PAFR, we now examined the role of these molecules in pulmonary inflammation induced by highly purified LTA in ..
  69. pmc TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta
    Jonathan C Kagan
    Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nat Immunol 9:361-8. 2008
    Toll-like receptor 4 (TLR4) induces two distinct signaling pathways controlled by the TIRAP-MyD88 and TRAM-TRIF pairs of adaptor proteins, which elicit the production of proinflammatory cytokines and type I interferons, respectively...
  70. pmc Group A streptococcus activates type I interferon production and MyD88-dependent signaling without involvement of TLR2, TLR4, and TLR9
    Nina Gratz
    Max F Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria
    J Biol Chem 283:19879-87. 2008
    ..GAS; Streptococcus pyogenes) does not require TLR2, a receptor implicated in sensing of Gram-positive bacteria, or TLR4 and TLR9...
  71. doi Chitin is a size-dependent regulator of macrophage TNF and IL-10 production
    Carla A Da Silva
    Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06519, USA
    J Immunol 182:3573-82. 2009
    ....
  72. ncbi Toll-like receptor 4 (TLR4) does not confer a resistance advantage on mice against low-dose aerosol infection with virulent type A Francisella tularensis
    Wangxue Chen
    Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Room 3100, Ottawa, Ontario, Canada K1A 0R6
    Microb Pathog 37:185-91. 2004
    ..To determine the role of TLR4 in host defense against airborne F...
  73. pmc The absence of Toll-like receptor 4 signaling in C3H/HeJ mice predisposes them to overwhelming rickettsial infection and decreased protective Th1 responses
    Jeffrey M Jordan
    Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 0609, USA
    Infect Immun 76:3717-24. 2008
    The importance of toll-like receptor 4 (TLR4) in immunity to rickettsiae remains elusive...
  74. pmc Toll-like receptor 4 signaling leads to severe fungal infection associated with enhanced proinflammatory immunity and impaired expansion of regulatory T cells
    Flávio V Loures
    Departamento de Imunologia, Instituto de Ciencias Biomedicas da Universidade de Sao Paulo, CEP 05508 900, Sao Paulo, SP, Brazil
    Infect Immun 78:1078-88. 2010
    ..The objective of this study was to characterize the involvement of TLR4 in the innate and adaptive immunity to Paracoccidioides brasiliensis, the most important primary fungal pathogen of ..
  75. pmc Differential expression of interferon regulatory factor 1 (IRF-1), IRF-2, and interferon consensus sequence binding protein genes in lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive macrophages
    S A Barber
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 4788
    Infect Immun 63:601-8. 1995
    Macrophages secrete interferon (IFN), as well as other cytokines, following lipopolysaccharide (LPS) stimulation...
  76. ncbi The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens
    D M Underhill
    Department of Immunology, University of Washington, Seattle 98195, USA
    Nature 401:811-5. 1999
    ....
  77. ncbi Infection of C57BL/10ScCr and C57BL/10ScNCr mice with Leishmania major reveals a role for Toll-like receptor 4 in the control of parasite replication
    P Kropf
    Faculty of Medicine, Division of Investigative Science, Department of Immunology, Norfolk Place, London, W2 1PG, United Kingdom
    J Leukoc Biol 76:48-57. 2004
    ..In the present study, we investigated the contribution of TLR4 to the course of cutaneous leishmaniasis in vivo...
  78. ncbi Chlamydia pneumoniae stimulates IFN-gamma synthesis through MyD88-dependent, TLR2- and TLR4-independent induction of IL-18 release
    Mihai G Netea
    Department of Medicine, University Medical Center Nijmegen, The Netherlands
    J Immunol 173:1477-82. 2004
    ..In contrast, C. pneumoniae stimulated the production of IL-18 through MyD88-dependent, TLR2-, TLR4-, and CD14-independent pathways, mediated by posttranscriptional mechanisms not involving de novo protein synthesis...
  79. ncbi Role of TLR in B cell development: signaling through TLR4 promotes B cell maturation and is inhibited by TLR2
    Elize A Hayashi
    Department of Immunology, Institute of Microbiology, Federal University of Rio de Janeiro, Brazil
    J Immunol 174:6639-47. 2005
    The role of TLR4 in mature B cell activation is well characterized. However, little is known about TLR4 role in B cell development...
  80. ncbi MyD88 is pivotal for the early inflammatory response and subsequent bacterial clearance and survival in a mouse model of Chlamydia pneumoniae pneumonia
    Yoshikazu Naiki
    Division of Pediatrics Infectious Diseases and Immunology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90048, USA
    J Biol Chem 280:29242-9. 2005
    ..with elevated IL-1beta and IFN-gamma leading to increased mortality, whereas wild-type mice as well as TLR2- or TLR4-deficient mice recovered from acute pneumonia and did not show delayed bacterial clearance...
  81. pmc Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria
    Vincent Feuillet
    Centre d immunologie de Marseille Luminy, Universite de la Mediterranee, Case 906, 13288 Marseille, France
    Proc Natl Acad Sci U S A 103:12487-92. 2006
    ..p. infection with S. typhimurium or intranasal administration of P. aeruginosa may be masked by TLR4 or other sensing mechanisms. By using radiation bone marrow chimera, we showed that upon i.p...
  82. pmc Enhancement of macrophage stimulation by lipoteichoic acid and the costimulant hemoglobin is dependent on Toll-like receptors 2 and 4
    Kathleen H Cox
    Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, 800 Madison Avenue, Memphis, Tennessee 38163, USA
    Infect Immun 75:2638-41. 2007
    ..results in a slight enhancement of IL-6 secretion in response to LTA plus Hb compared to that with LTA alone and is TLR4 independent. The second requires TLR4 and accounts for most of the additional stimulation seen with LTA plus Hb.
  83. pmc Control of Pseudomonas aeruginosa in the lung requires the recognition of either lipopolysaccharide or flagellin
    Reuben Ramphal
    Unité de Défense Innée et Inflammation, Institut Pasteur, Paris, France
    J Immunol 181:586-92. 2008
    ..aeruginosa strain. However, we now find that mice lacking both TLR2 and TLR4 (TLR2,4-/- mice) are hypersusceptible to infection following challenge with a P...
  84. pmc Differential regulation of the PGC family of genes in a mouse model of Staphylococcus aureus sepsis
    Timothy E Sweeney
    Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States of America
    PLoS ONE 5:e11606. 2010
    ..an established model of Staphylococcus aureus sepsis both in mice with impaired innate immune function (TLR2-/- and TLR4-/-) and in wild-type controls...
  85. ncbi Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis
    Mieke F Roelofs
    Department of Rheumatology Research and Advanced Therapeutics, Nijmegen Center for Molecular Life Sciences, The Netherlands
    J Immunol 176:7021-7. 2006
    ..In this study, we investigated whether five members of the small heat shock protein (HSP) family were involved in TLR4-mediated DC activation and whether these small HSPs were present in RA synovial tissue...
  86. pmc Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis
    Shahla Abdollahi-Roodsaz
    Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    J Clin Invest 118:205-16. 2008
    ..Here, we show that TLR2 and TLR4, but not TLR9, are involved in the pathogenesis of autoimmune arthritis and play distinct roles in the regulation ..
  87. pmc Construction of a BALB/c congenic mouse, C.C3H-Lpsd, that expresses the Lpsd allele: analysis of chromosome 4 markers surrounding the Lps gene
    S N Vogel
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
    Infect Immun 62:4454-9. 1994
    ..BALB/c mouse strain that contains a segment of chromosome 4 including the Lpsd allele of the lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ strain is presented...
  88. pmc Lipopolysaccharide-responder and nonresponder C3H mouse strains are equally susceptible to an induced Escherichia coli urinary tract infection
    W Hopkins
    Medical School, University of Wisconsin, Madison, USA
    Infect Immun 64:1369-72. 1996
    ..leading up to local inflammation are thought to be under genetic control and initiated by lipopolysaccharides (LPS) of gram-negative bacteria such as Escherichia coli...
  89. ncbi The role of MyD88 and TLR4 in the LPS-mimetic activity of Taxol
    C A Byrd-Leifer
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Eur J Immunol 31:2448-57. 2001
    ..Macrophages from C3H/HeJ mice, which have a spontaneous mutation in Toll-like receptor 4 (TLR4), are hyporesponsive to both LPS and Taxol, suggesting that LPS and Taxol may share a signaling pathway involving ..
  90. ncbi Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lung
    Xiaorong Wang
    Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Immunol 168:810-5. 2002
    ..This study characterizes the role of TLR4 in the innate immune response to intrapulmonary administration of Haemophilus influenzae in the mouse...
  91. pmc Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity
    Volaluck Supajatura
    Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan
    J Clin Invest 109:1351-9. 2002
    Toll-like receptor 2 (TLR2) and TLR4 play important roles in the early innate immune response to microbial challenge...
  92. pmc Toll-like receptor 4 on stromal and hematopoietic cells mediates innate resistance to uropathogenic Escherichia coli
    Joel D Schilling
    Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:4203-8. 2003
    ..the LPS-nonresponsive mouse strain C3HHeJ, which has a mutation in the primary LPS receptor, Toll-like receptor 4 (TLR4), is extremely susceptible to infection with uropathogenic strains of E. coli...
  93. ncbi Overexpression of Toll-like receptor 4 amplifies the host response to lipopolysaccharide and provides a survival advantage in transgenic mice
    Franck Bihl
    Department of Human Genetics, McGill University, and Center for the Study of Host Resistance, Montreal General Hospital, Montreal, Quebec, Canada
    J Immunol 170:6141-50. 2003
    ..Among them, Toll-like receptor 4 (Tlr4) is a crucial signal transducer for LPS, the major component of Gram-negative bacteria outer cell membrane...
  94. ncbi Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita Osaka 565 0871, Japan
    Science 301:640-3. 2003
    ..of a common MyD88-dependent signaling pathway as well as a MyD88-independent pathway that is unique to TLR3 and TLR4 signaling pathways leading to interferon (IFN)-beta production...
  95. pmc Role of Toll-like receptor 4 in gram-positive and gram-negative pneumonia in mice
    Judith Branger
    Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands
    Infect Immun 72:788-94. 2004
    To determine the role of Toll-like receptor 4 (TLR4) in the immune response to pneumonia, C3H/HeJ mice (which display a mutant nonfunctional TLR4) and C3H/HeN wild-type mice were intranasally infected with either Streptococcus pneumoniae (..
  96. pmc Kinase RIP3 is dispensable for normal NF-kappa Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4
    Kim Newton
    Molecular Oncology Department, Genentech, Inc, South San Francisco, California 94080, USA
    Mol Cell Biol 24:1464-9. 2004
    ..of the B- or T-cell antigen receptors; peptidoglycan, which activates Toll-like receptor 2; and lipopolysaccharide (LPS), which stimulates Toll-like receptor 4...
  97. ncbi Signaling for myocardial depression in hemorrhagic shock: roles of Toll-like receptor 4 and p55 TNF-alpha receptor
    Xianzhong Meng
    Dept of Surgery, Box C 320, University of Colorado Health Sciences Center, 4200 E 9th Avenue, Denver, CO 80262, USA
    Am J Physiol Regul Integr Comp Physiol 288:R600-6. 2005
    ..Toll-like receptor 4 (TLR4) regulates cellular expression of proinflammatory mediators following lipopolysaccharide stimulation and may be ..
  98. ncbi Toll-dependent control mechanisms of CD4 T cell activation
    Chandrashekhar Pasare
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Immunity 21:733-41. 2004
    ..In addition we show that a TLR-induced signal(s) is required for memory CD4 T cell differentiation, but not for activation of memory T cells...
  99. ncbi Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function
    Roman Spörri
    Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK
    Nat Immunol 6:163-70. 2005
    ....
  100. ncbi The radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in antibody response to microbial membranes
    Yoshinori Nagai
    Divisions of Infectious Genetics and Immunology, Institute of Medical Science, University of Tokyo, Japan
    J Immunol 174:7043-9. 2005
    ..RP105(-/-) B cells proliferated poorly in response to not only the TLR4 ligand LPS but also TLR2 ligand lipoproteins, both of which mediate the immunostimulatory activity of microbial ..
  101. ncbi Double-stranded RNA-mediated TLR3 activation is enhanced by CD14
    Hyun Ku Lee
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    Immunity 24:153-63. 2006
    ..However, TLR3 was localized in the lysosomes as was CD14 once the cells took up pIpC. We also observed that internalized pIpCsf colocalized with CD14 and TLR3. Consequently, CD14 mediates pIpC uptake and enhances TLR3 signaling...

Research Grants64

  1. MYCOPLASMA SUPERANTIGEN MAM IN DISEASE AND AUTOIMMUNITY
    Hong Hua Mu; Fiscal Year: 2003
    ..Specifically the investigator shall define the role played by SAg-induced cytokines and protection against disease using the MAM vaccines described earlier. ..
  2. Early Forms of Oxidized LDL, TLRs and Atherosclerosis
    Yury Miller; Fiscal Year: 2010
    ..published findings that mmLDL, but not extensively oxidized LDL,binds to CD14 and that this complex activates TLR4, resulting in cytoskeletal rearrangements and pro-inflammatory signaling and cytokine expression...
  3. Initiation of Contact and Asthmatic Hypersensitivity
    Philip Askenase; Fiscal Year: 2008
    ..abstract_text> ..
  4. Systems Approach to Innate Immunity-Inflammation-Sepsis
    Richard Ulevitch; Fiscal Year: 2006
    ..These studies will also identify potential new drug targets that could lead to new therapies for sepsis and shock. This would directly impact the clinical outcome of these critically ill patients...
  5. PE Biosystems TaqMan Quantitative PCR Model 7700
    Richard Ulevitch; Fiscal Year: 2001
    ..This instrument will be very important to the success of the projects of at least the eighteen research groups that are represented in this application. ..
  6. Mutagenic analysis of LPS responses
    Bruce Beutler; Fiscal Year: 2006
    The LPS signaling pathway has been analyzed using a combination of biochemical and genetic methods. Yet, to the present time, not all of the proteins that participate in LPS detection have been identified...
  7. American Society for Rickettsiology Conference 2006
    ROMAN GANTA; Fiscal Year: 2006
    ..abstract_text> ..
  8. Extracellular Matrix Protein in Innate Immunity
    You Wen He; Fiscal Year: 2007
    ..Mindin deficient mice are resistant to lipopolysaccharide (LPS) induced septic shock and produced low levels of inflammatory cytokines upon LPS challenge...
  9. Pattern Recognition Molecule Mindin As Adjuvant
    You Wen He; Fiscal Year: 2007
    ..Third, Mindin fused DNA plasmids will be examined for their efficacy in protecting influenza virus infection. [unreadable] [unreadable]..
  10. Analysis of CD81-PGRL complex on T cells
    STEPHEN CHAPES; Fiscal Year: 2007
    ..The coordinated effect of CD81, PGRL and EP3 on T cell integrin activity measured by adhesion to or motility on ICAMs. ..
  11. TLR4 as an LPS sendor and susceptibility locus
    Bruce Beutler; Fiscal Year: 2007
    ..In brief, the dsRNA receptor (TLR3) and the LPS receptor (TLR4) utilize a common TIR adapter molecule, disrupted by the Lps2 mutation...
  12. P. gingivalis lipid A species modulation of endothelial cell gene activation prog
    Richard Darveau; Fiscal Year: 2007
    ..gingivalis LPS preparations interact with TLR4. However, they have opposing effects on E selectin expression from human endothelial cells...
  13. Antipathogen Immunoadhesins
    Sanjay Ram; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  14. MECHANISMS OF NOVEL ANTI-INFLAMMATORY ACTIONS OF SLPI
    Aihao Ding; Fiscal Year: 2007
    ..Expression of both proteins is upregulated in macrophages by microbial products such as lipopolysaccharide (LPS). We have identified PEPI as a SLPI interacting protein...
  15. Genomics of Susceptibility to Urinary Tract Infections
    WALTER HOPKINS; Fiscal Year: 2007
    ..coli strains or non-E, coil bacteria. These objectives will be accomplished using a well-established mouse model of ascending UTI, genetic linkage analysis, and evaluation of resistance to uropathogens in congenic mice. ..
  16. Innate immune responses in lymphatic filariasis
    AMY HISE; Fiscal Year: 2007
    ..malayi extracts with competitive inhibitors of the LPS - TLR4 interaction suggest that the stimulatory effects of Brugia are exerted through both TLR4 and TLR4-independent ..
  17. Hepatitis C Virus, Alcohol and Host Defense
    Gyongyi Szabo; Fiscal Year: 2007
    ..Results from these studies should reveal molecular and cellular mechanisms by which alcohol interacts with HCV infection to accelerate disease persistence and progression. [unreadable] [unreadable]..
  18. Immunological Basis for H. Pylori-Related Malignancies
    Marygorret Obonyo; Fiscal Year: 2006
    ..Under this award, the candidate will be able to develop this work into a productive project that will gain independent funding. ..
  19. Macrophage defense againt M. tuberculosis
    Jennifer Wang; Fiscal Year: 2008
    ..abstract_text> ..
  20. Respiratory Immunity Against Agents of Bioterrorism
    STEVEN MIZEL; Fiscal Year: 2008
    ....
  21. Role of E. coli Virulence Factors in Chronic Prostate Infection and Inflammation
    WALTER HOPKINS; Fiscal Year: 2008
    ..coli genes play a direct or indirect role in development of prostatic lesions. Results of these studies can lead to new methods to prevent or treat chronic bacterial prostatitis. [unreadable] [unreadable] [unreadable]..
  22. MECHANISMS OF IMMUNOSUPPRESSION BY ONE DOSE OF ETHANOL
    Stephen Pruett; Fiscal Year: 2007
    ..oxide synthase (iNOS) production induced by a ligand for TLR 3 (poly I:C) and TLR 4 (bacterial lipopolysaccharide, LPS)...
  23. Ethanols role in mediation of monocyte suppression
    Gyongyi Szabo; Fiscal Year: 2009
    ..Investigation of the modulation of IL-10 and IL-12 by alcohol in dendritic cell function may identify biomarkers of alcohol-induced immune depression and reveal potential targets for therapy. ..
  24. B1B lymphocytes generate T cell-independent memory
    KISHORE ALUGUPALLI; Fiscal Year: 2009
    ..Understanding the basis for the longevity of the Tl protective responses conferred by B1b cells will provide novel approaches to generate effective vaccines against pathogens expressing Tl antigens. ..
  25. KUPFFER CELLS AND CHEMICAL TOXICITY
    Debra Laskin; Fiscal Year: 2009
    ..Mechanistic insights derived from these studies may suggest new therapeutic approaches in the treatment of acute liver injury induced by acetaminophen. ..
  26. Glial Interactions in Premyelinating Oligodendrocyte Destruction
    Jianrong Li; Fiscal Year: 2010
    ..Recently, we showed that microglia, activated by lipopolysaccaride (LPS), selectively kill pre-OLs by producing peroxynitrite...
  27. GENERAL CLINICAL RESEARCH CENTER
    Kevin J Tracey; Fiscal Year: 2010
    ..This proposal seeks continued funding for the Feinstein GCRC by NCRR. ..
  28. IKKBeta Mediated Impairment of Endothelial Nitric Oxide Production
    Francis Kim; Fiscal Year: 2010
    ..Aim 3. To determine whether the Toll Like Receptor pathway is necessary for endothelial activation of IKKbeta during the development of vascular insulin resistance. ..
  29. Mechanisms of methyl dithiocarbamate immunotoxicity
    Stephen B Pruett; Fiscal Year: 2010
    ..This project will test the following hypothesis: SMD alters signaling through TLR4 to decrease the production of IL-12 and to increase IL-10 production by altering cellular redox balance, altering ..
  30. Forward Genetic Analysis of the Innate Immune Contribution to MCMV Resistance
    Bruce Beutler; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  31. FORMATION AND SURVIVAL OF RED BLOOD CELLS
    Ernest Beutler; Fiscal Year: 2001
    ..Should these point mutations fail to alter gene transcription, a search will be made for other potential mutations in linkage disequilibrium with the known -5,-8 and -24 polymorphisms, by sequencing upstream through the promotor. ..
  32. Cellular Immunity Against Ehrlichia chaffeensis
    ROMAN GANTA; Fiscal Year: 2002
    ..chaffeensis and other closely related organisms. ..
  33. Bacterial infection induces cytokine production
    Ian Marriott; Fiscal Year: 2003
    ..abstract_text> ..
  34. Competition Among Bacterial Resiratory Pathogens
    Jeffrey Weiser; Fiscal Year: 2004
    ..In addition, a neuraminidase expressed by S. pneumoniae can desialylate host receptors and the sialylated LPS of H. influenzae...
  35. URINARY TRACT INFECTIONS--IMMUNE BASIS OF SUSCEPTIBILITY
    WALTER HOPKINS; Fiscal Year: 2003
    ....
  36. ANTITUMOR IMMUNITY INDUCED BY FUSION CELLS VACCINATION
    Jianlin Gong; Fiscal Year: 2003
    ..3). To assess the effectiveness of fusion cell vaccines in the prevention and treatment of spontaneous breast carcinoma in transgenic mice. ..
  37. REGULATION OF MICROVASCULAR PERMEABILITY BY NITRIC OXIDE
    ROLANDO RUMBAUT; Fiscal Year: 2004
    ..The long-term goal is to apply the knowledge gained from these studies to allow optimal management of patients with these important clinical entities and their associated microvascular alterations. ..
  38. MOLECULAR PATHOLOGY OF LPS-INDUCED INJURY
    Richard Ulevitch; Fiscal Year: 2004
    ..b>LPS will be used as a prototype of bacterial toxins in order to characterize the functional role of the components of ..
  39. Osteoblast-derived inflammatory mediators in infection
    Ian Marriott; Fiscal Year: 2004
    ..aureus by the production of this pivotal inflammatory molecule, thereby expanding the recognized role of these cells to include being key components in host responses during bone infection. ..
  40. Identification of E. histolytica virulence factors
    Molly Hughes; Fiscal Year: 2004
    ..Successful completion of these studies will yield a fundamental understanding of amebic proteins that interact with the E. histolytica GalNAc lectin and their role in pathogenicity. ..
  41. Studies on Macrophage Resistance to Anthrax Lethal Toxin
    Molly Hughes; Fiscal Year: 2004
    ..Successful completion of these studies will yield a fundamental understanding of mechanisms of macrophage resistance to LT. ..
  42. 37th Annual Meeting of the Society for Leukocyte Biology
    Joshua Fierer; Fiscal Year: 2004
    ..We encourage students and other trainees to submit abstracts; the SLB gives awards for the best abstracts submitted by students. One of the main purposes of the meeting is to encourage young scientists. ..
  43. A Mouse Model of Gaucher Disease
    Ernest Beutler; Fiscal Year: 2005
    ..In particular, electron microscopy and light microscopy will be used to attempt to demonstrate the development of Gaucher cells in the chimeric mice. ..
  44. Mechanisms of Immunotoxcity of Chemical Stressors
    Stephen Pruett; Fiscal Year: 2005
    ....
  45. ORPHAN NUCLEAR RORgammat IN THYMOCYTE DIFFERENTIATION
    You Wen He; Fiscal Year: 2006
    ..In addition, results from this application will also provide insights for the role of ROR-gamma-t in tumorigenesis. ..
  46. Heat Shock Proteins and Helicobacter Pylori Pathogenesis
    Evelyn Kurt Jones; Fiscal Year: 2006
    ..Specifically, we will use in vitro and in vivo approaches to investigate the role of heat shock proteins in H. pylori infection and pathogenesis and development of tumors. ..
  47. Genes that Mediate Tolerance to the Placental Allograft
    Bruce Beutler; Fiscal Year: 2006
    ..Fourth, circumvention of the toleragenic mechanism might be used to prevent normal gestation, leading to termination of pregnancy within a few days following implantation of the blastocyst. ..
  48. Pathogenesis of Endotoxin-Induced Acute Renal Failure
    Patrick Cunningham; Fiscal Year: 2006
    ..abstract_text> ..
  49. Mycoplasma Superantigen & RA MHC Susceptibility Alleles
    BARRY COLE; Fiscal Year: 2006
    ..arthritidis in these "humanized" mice and determine strategies to overcome the effect of the superantigen MAM in initiating disease pathogenesis by modification of the cytokine milieu. ..
  50. Activation of inflammatory cells by flagellin
    STEVEN MIZEL; Fiscal Year: 2006
    ..Flagellin signaling is mediated by a toll-like receptor (TLR) protein, TLR5, but can be modulated by another TLR, TLR4. In view of the extraordinary potency of flagellin as an activator of cells that are involved in host defense, we ..
  51. Tracking Mucosal T cells to Commensal Microbes in Vivo
    Massimo Costalonga; Fiscal Year: 2006
    ..The data will be important to human health, establishing a framework to study in vivo mucosal infectious agents and oral vaccines. ..
  52. American Society for Rickettsiology conference
    ROMAN GANTA; Fiscal Year: 2005
    ..abstract_text> ..
  53. ASM Conf. on Beneficial Microbial Symbionts in Animals
    Richard Darveau; Fiscal Year: 2005
    ..It is an intellectually stimulating subject that attracts pioneering graduate students and post-doctoral fellows who will benefit from participation in a focused and dynamic conference; ..
  54. Mechanisms of Alcohol Mediated Organ and Tissue Damage
    Gyongyi Szabo; Fiscal Year: 2005
    ..3. Increase the involvement of young investigators in the study of alcohol research. 4. Provide an educational forum to participants. ..
  55. Innate Immunity to Salmonella Infections
    Joshua Fierer; Fiscal Year: 2005
    ..We will compare isogenic strains of salmonella that express either the group B or 0 LPS antigens in C3 deficient and neutropenic mice, in order to determine how the structure of the LPS affects virulence ..
  56. Host Immunoregulation of Response to Antileishmanial Chemotherapy
    Henry Murray; Fiscal Year: 2007
    ..abstract_text> ..
  57. MECHANISMS OF MICROVASCULAR THROMBOSIS IN ENDOTOXEMIA
    ROLANDO RUMBAUT; Fiscal Year: 2009
    ..Our central hypothesis is that LPS-induced stimulation of toll-like receptor 4 (TLR4) on endothelial cells mediates microvascular thrombosis in endotoxemia, by a mechanism dependent on the platelet ..
  58. BRAIN GALANIN RECEPTORS AND EPILEPSY
    Andrey Mazarati; Fiscal Year: 2006
    ..abstract_text> ..
  59. Functional role of Angiopoietin-2 in diabetic heart
    Jian xiong Chen; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  60. Oral Commensal Bacterial Modulation of the Periodontal Innate Host Response
    RICHARD PETERS DARVEAU; Fiscal Year: 2010
    ..n Specific Aim 3 changes in gingival epithelial cell TLR2 and TLR4 expression levels that may alter commensal homeostasis with the host will be determined...
  61. Mouse model of oral infection with virulent Francisella
    Wangxue Chen; Fiscal Year: 2005
    ..tularensis infection so that future hypothesis-driven studies with more focused research objectives can be designed and developed. ..
  62. BACTERIAL PHOSPHORYLCHOLINE AND PATHOGENESIS
    Jeffrey Weiser; Fiscal Year: 2009
    ..Aim 3 will determine the effects of the immune response to ChoP on colonization, where our findings demonstrate that expression of ChoP is most important to pathogenesis. ..