interleukin 1 receptors

Summary

Summary: Specific molecular sites or structures on cells with which interleukin-1 reacts or to which it binds to modify the function of the cells. The IL-1 receptor on T-lymphocytes and fibroblasts is composed of a single polypeptide chain that binds both IL-1 alpha and IL-1 beta. The molecular weight of this high-affinity receptor is believed to be 80 kD.

Top Publications

  1. ncbi Biologic basis for interleukin-1 in disease
    C A Dinarello
    Department of Medicine, Tufts University, Boston, MA USA
    Blood 87:2095-147. 1996
  2. 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
  3. ncbi Interleukin-1 receptor antagonist: role in biology
    W P Arend
    Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA
    Annu Rev Immunol 16:27-55. 1998
  4. ncbi Structural basis for signal transduction by the Toll/interleukin-1 receptor domains
    Y Xu
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 408:111-5. 2000
  5. ncbi Negative regulation of toll-like receptor-mediated immune responses
    Foo Y Liew
    Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow G11 6NT, UK
    Nat Rev Immunol 5:446-58. 2005
  6. ncbi IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
    Jochen Schmitz
    Schering Plough Biopharma Formerly DNAX Research, Inc, 901 California Avenue, Palo Alto, California 94304, USA
    Immunity 23:479-90. 2005
  7. ncbi TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells
    Marc Veldhoen
    Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    Immunity 24:179-89. 2006
  8. ncbi The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors
    Tiffany Horng
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 420:329-33. 2002
  9. pmc T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses
    M J Townsend
    Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
    J Exp Med 191:1069-76. 2000
  10. ncbi Toll-like receptors: critical proteins linking innate and acquired immunity
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Nat Immunol 2:675-80. 2001

Detail Information

Publications295 found, 100 shown here

  1. ncbi Biologic basis for interleukin-1 in disease
    C A Dinarello
    Department of Medicine, Tufts University, Boston, MA USA
    Blood 87:2095-147. 1996
    ..At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease...
  2. 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
    ..Instead, TIRAP has a crucial role in the MyD88-dependent signalling pathway shared by TLR2 and TLR4...
  3. ncbi Interleukin-1 receptor antagonist: role in biology
    W P Arend
    Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA
    Annu Rev Immunol 16:27-55. 1998
    ..However, patients with rheumatoid arthritis treated with IL-1Ra for six months exhibited improvements in clinical parameters and in radiographic evidence of joint damage...
  4. ncbi Structural basis for signal transduction by the Toll/interleukin-1 receptor domains
    Y Xu
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 408:111-5. 2000
    ....
  5. ncbi Negative regulation of toll-like receptor-mediated immune responses
    Foo Y Liew
    Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow G11 6NT, UK
    Nat Rev Immunol 5:446-58. 2005
    ..Here, we discuss the various negative regulatory mechanisms that have evolved to attenuate TLR signalling to maintain this immunological balance...
  6. ncbi IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
    Jochen Schmitz
    Schering Plough Biopharma Formerly DNAX Research, Inc, 901 California Avenue, Palo Alto, California 94304, USA
    Immunity 23:479-90. 2005
    ..In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs...
  7. ncbi TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells
    Marc Veldhoen
    Division of Molecular Immunology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    Immunity 24:179-89. 2006
    ..Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells...
  8. ncbi The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors
    Tiffany Horng
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 420:329-33. 2002
    ..Thus, TIRAP is differentially involved in signalling by members of the TLR family and may account for specificity in the downstream signalling of individual TLRs...
  9. pmc T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type 2 responses
    M J Townsend
    Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
    J Exp Med 191:1069-76. 2000
    ..These data clearly demonstrate that T1/ST2 expression plays a role in the development of Th2-like cytokine responses and indicate that effector functions are inhibited in its absence...
  10. ncbi Toll-like receptors: critical proteins linking innate and acquired immunity
    S Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565 0871, Japan
    Nat Immunol 2:675-80. 2001
    ..Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--..
  11. ncbi Toll-like receptor signalling
    Shizuo Akira
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Agency, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Rev Immunol 4:499-511. 2004
  12. pmc Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion
    R Horai
    Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108, Japan
    J Exp Med 187:1463-75. 1998
    ..The importance of IL-1ra both in normal physiology and under stress is also suggested...
  13. ncbi TIRAP: an adapter molecule in the Toll signaling pathway
    T Horng
    Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Nat Immunol 2:835-41. 2001
    ..We have also shown that the double-stranded RNA-binding protein kinase PKR is a component of both the TIRAP- and MyD88-dependent signaling pathways...
  14. pmc The absence of interleukin 1 receptor-related T1/ST2 does not affect T helper cell type 2 development and its effector function
    K Hoshino
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    J Exp Med 190:1541-8. 1999
    ..In addition, differentiation and function of bone marrow-derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells...
  15. ncbi SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling
    David Wald
    Cleveland Clinic Foundation, Department of Immunology, Cleveland, Ohio 44195, USA
    Nat Immunol 4:920-7. 2003
    ..Finally, biochemical analysis indicated that SIGIRR binds to the TLR-IL-1R signaling components in a ligand-dependent way. Our data show that SIGIRR functions as a biologically important modulator of TLR-IL-1R signaling...
  16. ncbi Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis
    James W Verbsky
    Division of Rheumatology, Department of Pediatrics, Washington University School of Medicine, St Lousis Children s Hospital, Missouri 63110, USA
    J Rheumatol 31:2071-5. 2004
    ..Both patients experienced immediate and sustained resolution of symptoms and laboratory markers of inflammation, in one case after years of treatment with other immunosuppressive therapies...
  17. ncbi Abnormal T cell activation caused by the imbalance of the IL-1/IL-1R antagonist system is responsible for the development of experimental autoimmune encephalomyelitis
    Taizo Matsuki
    Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato ku, Tokyo 108 8639, Japan
    Int Immunol 18:399-407. 2006
    ..These observations suggest that the IL-1/IL-1Ra system is crucial for auto-antigen-specific T cell induction and contributes to the development of EAE...
  18. pmc A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis
    Caroline Sutton
    Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland
    J Exp Med 203:1685-91. 2006
    ..Tumor necrosis factor alpha also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE...
  19. ncbi The importance of IL-1 beta and TNF-alpha, and the noninvolvement of IL-6, in the development of monoclonal antibody-induced arthritis
    Takashi Kagari
    Biological Research Laboratories, Sankyo Co, Ltd, Tokyo, Japan
    J Immunol 169:1459-66. 2002
    ..Because arthritis was also developed in SCID mice, the development of arthritis in the Ab-induced mice model is due to a mechanism that does not involve T or B cells...
  20. ncbi Interleukin-1-receptor antagonist in the Muckle-Wells syndrome
    Philip N Hawkins
    N Engl J Med 348:2583-4. 2003
  21. 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
    ..Our data emphasize a unifying theme in innate immune recognition whereby all type I interferon-inducing receptors signal from an intracellular location...
  22. ncbi A putative protein of a growth specific cDNA from BALB/c-3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor
    S Tominaga
    Okinaka Memorial Institute for Medical Research, Tokyo, Japan
    FEBS Lett 258:301-4. 1989
    ..The immunoglobulin superfamily is believed to be involved in cell adhesion and cell-to-cell interaction. The evidence that a member of this family is induced in the course of the initiation of cell proliferation is intriguing...
  23. ncbi IL-1 receptor-associated kinase modulates host responsiveness to endotoxin
    J L Swantek
    Departments of Pharmacology, Pediatrics, and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA
    J Immunol 164:4301-6. 2000
    ..These findings, coupled with the critical role for IRAK in IL-1 and IL-18 signal transduction, demonstrate the importance of this kinase and the IL-1/Toll signaling cassette in sensing and responding to Gram-negative infection...
  24. pmc MyD88-dependent and -independent signaling by IL-1 in neurons probed by bifunctional Toll/IL-1 receptor domain/BB-loop mimetics
    Christopher N Davis
    The Harold L Dorris Neurological Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 103:2953-8. 2006
    ....
  25. ncbi ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance
    Elizabeth K Brint
    Department of Biochemistry, Trinity College, Dublin 2, Ireland
    Nat Immunol 5:373-9. 2004
    ..Thus, these results provide a molecular explanation for the function of ST2 in T(H)2 responses, as inhibition of TLRs promotes a T(H)2 response, and also identify ST2 as a key regulator of endotoxin tolerance...
  26. pmc Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection
    Nicole Schmitz
    Molecular Biomedicine, ETH Zurich, Wagistrasse 27, 8952 Zurich, Switzerland
    J Virol 79:6441-8. 2005
    ..IL-1alpha/beta appear not to influence killing of virus-infected cells but to enhance IgM antibody responses and recruitment of CD4(+) T cells to the site of infection...
  27. pmc Pyogenic bacterial infections in humans with MyD88 deficiency
    Horst von Bernuth
    Human Genetics of Infectious Diseases, INSERM U550, Paris, France
    Science 321:691-6. 2008
    ..The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections...
  28. ncbi Structures of the toll-like receptor family and its ligand complexes
    Mi Sun Jin
    Department of Chemistry and Institute for the BioCentury, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Daejeon, 305 701, Korea
    Immunity 29:182-91. 2008
    ..This observation suggests the hypothesis that dimerization of the extracellular domains forces the intracellular TIR domains to dimerize, and this initiates signaling by recruiting intracellular adaptor proteins...
  29. 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
    ..TLR4- but not TLR3-mediated MyD88-independent interferon-beta production and activation of signaling cascades were abolished in TRAM-deficient cells. Thus, TRAM provides specificity for the MyD88-independent component of TLR4 signaling...
  30. ncbi Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist
    S P Eisenberg
    Synergen Inc, Boulder, Colorado 80301
    Nature 343:341-6. 1990
    ..The sequence of the receptor antagonist indicates that it is structurally similar to IL-1 beta. Expression of the cDNA in Escherichia coli yields IL-1 receptor antagonist activity...
  31. ncbi Peptide-mediated interference of TIR domain dimerization in MyD88 inhibits interleukin-1-dependent activation of NF-{kappa}B
    Maria Loiarro
    Department of Public Health and Cell Biology, University of Rome Tor Vergata, 00173 Rome, Italy
    J Biol Chem 280:15809-14. 2005
    ..Our results indicate that the BB-loop in TIR domain of MyD88 is a good target for specific inhibition of MyD88-mediated signaling in vivo...
  32. ncbi Interleukin-1 receptor antagonist prevents embryonic implantation by a direct effect on the endometrial epithelium
    C Simon
    Instituto Valenciano de Infertilidad and Department of Pediatrics, Obstetrics, and Gynecology, Valencia University, Spain
    Fertil Steril 70:896-906. 1998
    ..To investigate the embryonic and/or endometrial molecular mechanisms underlying the antiimplantation effect of interleukin-1 receptor antagonist (IL-1ra)...
  33. ncbi Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage
    S B Abramson
    Department of Rheumatology, Hospital for Joint Diseases, New York University of Medicine, 301 East 17th Street, New York, NY 10003, USA
    Rheumatology (Oxford) 41:972-80. 2002
    ..These results demonstrate that blocking IL-1 protects bone and cartilage from progressive destruction in RA...
  34. ncbi Molecular cloning of the murine ST2 gene. Characterization and chromosomal mapping
    S Tominaga
    Department of Biochemistry II, Jichi Medical School, Tochigi, Japan
    Biochim Biophys Acta 1090:1-8. 1991
    ..The murine ST2 gene, which was expressed only in the growth-stimulated BALB/c-3T3 cells, was mapped to mouse chromosome one, very tightly linked to the interleukin 1 receptor-type 1 locus...
  35. ncbi IL-1 signaling cascade in liver cells and the involvement of a soluble form of the IL-1 receptor accessory protein
    L E Jensen
    Department of Pharmacology, Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Immunol 164:5277-86. 2000
    ..This suggests that sIL-1RAcP may act as an inhibitor of IL-1 by directly interacting with IL-1RI to abolish its capacity to transduce signal...
  36. ncbi Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q
    M Dale
    Division of Molecular and Genetic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield, S10 2JF, United Kingdom
    Genomics 57:177-9. 1999
    ..The only known family member that is absent from the human contig is the IL-1 receptor accessory protein gene (IL1RAP), which maps to 3q28...
  37. pmc Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling
    Hidenori Ohnishi
    Department of Pediatrics, Graduate School of Medicine, Center for Emerging Infectious Diseases, and Center for Advanced Drug Research, Gifu University, Gifu, Japan
    Proc Natl Acad Sci U S A 106:10260-5. 2009
    ..These observations suggested that the heteromeric assembly of TIR domains of the receptor and adaptors constitutes the initial step of TLR4 intracellular signal transduction...
  38. ncbi The IL-1 receptor 1 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model
    Nicole Schmitz
    Molecular Biomedicine, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland
    Eur J Immunol 33:991-1000. 2003
    ..These results suggest a critical role of IL-1/IL-1R1 for development of allergic Th2 responses, but its requirement can be overcome by using alum as adjuvant for sensitization...
  39. ncbi Pyogenic bacterial infections in humans with IRAK-4 deficiency
    Capucine Picard
    Laboratoire de Genetique Humaine des Maladies Infectieuses, Université René Descartes INSERM U550, Faculte Necker, 156 rue de Vaugirard, 75015 Paris, France
    Science 299:2076-9. 2003
    ..These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms...
  40. ncbi IL-1 enhances T cell-dependent antibody production through induction of CD40 ligand and OX40 on T cells
    S Nakae
    Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    J Immunol 167:90-7. 2001
    ..These observations indicate that IL-1 enhances T cell-dependent Ab production by augmenting CD40 ligand and OX40 expression on T cells...
  41. ncbi A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist
    H Schreuder
    Marion Merrell Dow Research Institute, Strasbourg, France
    Nature 386:194-200. 1997
    ..Modelling studies suggest that this IL-1beta trigger site might induce a movement of domain 3...
  42. ncbi Interleukin-1 receptor signaling mediates atherosclerosis associated with bacterial exposure and/or a high-fat diet in a murine apolipoprotein E heterozygote model: pharmacotherapeutic implications
    Hunghui Chi
    Department of Periodontology and Oral Biology, School of Dental Medicine, Boston University, Boston, MA 02118, USA
    Circulation 110:1678-85. 2004
    ..Studies presented here tested the hypothesis that IL-1 receptor (IL-1R1) signaling plays a crucial role in bacteria- and/or high-fat diet (HFD)-enhanced atherogenesis...
  43. ncbi Regulation of interleukin-1- and lipopolysaccharide-induced NF-kappaB activation by alternative splicing of MyD88
    Sophie Janssens
    Department of Molecular Biology, Unit of Molecular Signal Transduction in Inflammation, Gent University VIB, K L Ledeganckstraat 35, B 9000 Gent, Belgium
    Curr Biol 12:467-71. 2002
    ..Moreover, the regulated expression and antagonistic activity of MyD88(S) suggest an important role for alternative splicing of MyD88 in the regulation of the cellular response to IL-1 and LPS...
  44. ncbi The IL-1 family and inflammatory diseases
    C A Dinarello
    Department of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Ave, B168, Denver, CO 80262, USA
    Clin Exp Rheumatol 20:S1-13. 2002
    ..This property, of IL-1 is not observed in the responses to TNFalpha. Furthermore, in animal models of destructive rheumatoid arthritis, IL-1 is necessary but TNFalpha is not...
  45. ncbi TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme
    L Verstrepen
    Department of Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium
    Cell Mol Life Sci 65:2964-78. 2008
    ..In this review, we will discuss our current knowledge of NF-kappaB signaling in response to TLR-4, TNF-R and IL-1R stimulation, with a special focus on the similarities and dissimilarities among these pathways...
  46. ncbi Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
    K A Fitzgerald
    Department of Biochemistry, Trinity College, Dublin 2, Ireland
    Nature 413:78-83. 2001
    ..Mal associates with TLR-4. Mal is therefore an adapter in TLR-4 signal transduction...
  47. pmc Critical roles for interleukin 1 and tumor necrosis factor alpha in antibody-induced arthritis
    Hong Ji
    Section on Immunology and Immunogenetics, Joslin Diabetes Center and Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    J Exp Med 196:77-85. 2002
    ..The variability in the requirement for TNF-alpha, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes...
  48. pmc TNF-alpha is crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice
    Reiko Horai
    Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    J Clin Invest 114:1603-11. 2004
    ..These findings suggest that IL-1 receptor antagonist deficiency in T cells disrupts homeostasis of the immune system and that TNF-alpha plays an important role in activating T cells through induction of OX40...
  49. ncbi Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain responsible for coupling to the IL1beta signaling pathway
    Chunsheng Li
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 2363, USA
    J Biol Chem 280:26152-9. 2005
    ..Mutations in Box 2 and 3 prevented homotypic MyD88 oligomerization via TIR domain. Based on this structure-function analysis, a three-dimensional docking model of TIR-TIR interaction between MyD88 and IL1RAcP was developed...
  50. pmc Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses
    A J Coyle
    Department of Biology, Inflammation Division, Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
    J Exp Med 190:895-902. 1999
    ..Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses...
  51. pmc Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets
    Kathrin Maedler
    Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland
    J Clin Invest 110:851-60. 2002
    ..These findings implicate an inflammatory process in the pathogenesis of glucotoxicity in type 2 diabetes and identify the IL-1beta/NF-kappaB pathway as a target to preserve beta cell mass and function in this condition...
  52. ncbi cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily
    J E Sims
    Immunex Corporation, Seattle, WA 98101
    Science 241:585-9. 1988
    ..The extracellular, IL-1 binding portion of the receptor is 319 amino acids in length and is composed of three immunoglobulin-like domains. The cytoplasmic portion of the receptor is 217 amino acids long...
  53. pmc A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis
    Chiea C Khor
    The Wellcome Trust Centre for Human Genetics, University of Oxford, UK
    Nat Genet 39:523-8. 2007
    ..6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction...
  54. pmc Identification of critical residues of the MyD88 death domain involved in the recruitment of downstream kinases
    Maria Loiarro
    Department of Public Health and Cell Biology, University of Rome Tor Vergata, 00133 Rome, Italy
    J Biol Chem 284:28093-103. 2009
    ..These experiments identify novel residues of MyD88 that are crucially involved in the recruitment of IRAK1 and IRAK4 and in downstream propagation of MyD88 signaling...
  55. ncbi Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor
    K Burns
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Centre, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nat Cell Biol 2:346-51. 2000
    ..As overexpression of Tollip results in impaired NF-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway...
  56. ncbi IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling
    M Muzio
    University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA
    Science 278:1612-5. 1997
    ..Dominant negative forms of either attenuate IL-1R-mediated NF-kappaB activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation...
  57. pmc IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase
    Shyun Li
    Tularik, Inc, 2 Corporate Drive, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 99:5567-72. 2002
    ....
  58. ncbi IL-1, IL-18, and IL-33 families of cytokines
    William P Arend
    Division of Rheumatology, University of Colorado Denver, School of Medicine, Denver, CO, USA
    Immunol Rev 223:20-38. 2008
    ..IL-18 provides an important link between the innate and adaptive immune responses. Newly described IL-33 binds to the orphan IL-1 family receptor T1/ST2 and stimulates T-helper 2 responses as well as mast cells...
  59. ncbi IL-1 receptor type 1 gene-deficient mice demonstrate an impaired host defense against pneumococcal meningitis
    Petra J G Zwijnenburg
    Department of Pediatrics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands
    J Immunol 170:4724-30. 2003
    ..The mortality was significantly higher and earlier in the course of the disease in IL-1R(-/-) mice. These results demonstrate that endogenous IL-1 is required for an adequate host defense in pneumococcal meningitis...
  60. ncbi TIRAP mediates endotoxin-induced NF-kappaB activation and apoptosis in endothelial cells
    Douglas D Bannerman
    Department of Surgery, University of Washington School of Medicine, Seattle, WA 98104, USA
    Biochem Biophys Res Commun 295:157-62. 2002
    ..These data identify TIRAP as a dual functioning signaling molecule and suggest the presence of a MyD88-independent LPS signaling pathway in human endothelial cells...
  61. ncbi The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress
    Luke A J O'Neill
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland
    Immunol Rev 226:10-8. 2008
    ..This area has therefore proved very fruitful in terms of improving our knowledge of the molecular basis for innate immunity and inflammation, and we can anticipate further discoveries in the coming years...
  62. ncbi A novel negative regulator for IL-1 receptor and Toll-like receptor 4
    Foo Y Liew
    Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow G11 6NT, UK
    Immunol Lett 96:27-31. 2005
    ..The results provide a molecular explanation for the role of ST2 in T(H)2 responses since inhibition of TLRs will promote a T(H)2 response and also identify ST2 as a key regulator of endotoxin tolerance...
  63. pmc Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein
    J Huang
    Tularik, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 94:12829-32. 1997
    ..Overexpression of an IL-1RAcP mutant lacking its intracellular domain, the IRAK-binding domain, prevented the recruitment of IRAK to the receptor complex and blocked IL-1-induced NF-kappaB activation...
  64. ncbi Interleukin-1
    E Stylianou
    School of Medical and Surgical Sciences, University Hospital, Queen s Medical Centre, Nottingham, UK
    Int J Biochem Cell Biol 30:1075-9. 1998
    ..Phase I clinical trials of the soluble type I receptor and IRAP indicate that these have potential anti-inflammatory effects...
  65. ncbi Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression
    S Laye
    Institut National de la Recherche Agronomique Institut National de la Santé et de la Recherche Médicale Unité 394, Neurobiologie Integrative, 33077 Bordeaux, France
    Am J Physiol Regul Integr Comp Physiol 279:R93-8. 2000
    ..These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus...
  66. ncbi Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies
    Hal M Hoffman
    Division of Rheumatology and Allergy Immunology, University of California at San Diego, La Jolla, CA 92093 0635, USA
    Arthritis Rheum 58:2443-52. 2008
    ....
  67. ncbi Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4
    F Colotta
    Centro Daniela e Catullo Borgomainerio, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Science 261:472-5. 1993
    ..The existence of multiple pathways of regulation emphasizes the need for tight control of IL-1 action...
  68. ncbi Different pattern of interleukin-1 beta-(IL-1 beta), interleukin-1 receptor antagonist- (IL-1ra) and interleukin-1 receptor type I- (IL-1R tI) mRNA-expression in single preimplantation mouse embryos at various developmental stages
    J S Kruessel
    Department of Gynecology and Obstetrics, Stanford University School of Medicine, Palo Alto, California 94304, USA
    J Reprod Immunol 34:103-20. 1997
    ..IL-1ra mRNA seems to be expressed in a very high percentage (74%) of embryos near the time of implantation, whereas the percentage of IL-1 beta-mRNA positive embryos is surprisingly low (19%)...
  69. ncbi Mouse IL-1 receptor antagonist isoforms: complementary DNA cloning and protein expression of intracellular isoform and tissue distribution of secreted and intracellular IL-1 receptor antagonist in vivo
    C Gabay
    Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA
    J Immunol 159:5905-13. 1997
    ..Using RPA, primer extension assay and 5' rapid amplification of cDNA ends, we were able to demonstrate the presence of different transcription start sites for murine sIL-1Ra mRNA...
  70. ncbi Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling
    Hiroshi Takatsuna
    Division of Cellular and Molecular Biology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Biol Chem 278:12144-50. 2003
    ..Thus, TIFA is likely to mediate IRAK-1/TRAF6 interaction upon IL-1 stimulation...
  71. ncbi The IL-1 receptor accessory protein is essential for PI 3-kinase recruitment and activation
    Shrikanth A G Reddy
    Department of Gastrointestinal Medical Oncology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Biochem Biophys Res Commun 316:1022-8. 2004
    ..Thus, our results identified a functional region in the IL-1R AcP required for the recruitment and activation of PI 3-kinase...
  72. ncbi TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction
    Hiroyuki Oshiumi
    Department of Immunology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari ku, Japan
    Nat Immunol 4:161-7. 2003
    ..Thus, dsRNA-TLR3-dependent production of IFN-beta is mediated mainly by TICAM-1. This TICAM-1-dependent pathway may have a role in other TLR-IFN-beta pathways, which form part of the MyD88-independent cellular immune response...
  73. pmc Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene
    M J Nicklin
    Division of Molecular and Genetic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom
    J Exp Med 191:303-12. 2000
    ....
  74. pmc Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4
    Kimberly Burns
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH 1066 Epalinges, Switzerland
    J Exp Med 197:263-8. 2003
    ..Thus, MyD88s acts as a negative regulator of IL-1R/TLR/MyD88-triggered signals, leading to a transcriptionally controlled negative regulation of innate immune responses...
  75. ncbi Phosphatidylinositol 3-kinase is recruited to a specific site in the activated IL-1 receptor I
    S Marmiroli
    Istituto di Citomorfologia Normale e Patologica del C N R, Bologna, Italy
    FEBS Lett 438:49-54. 1998
    ..Our results indicate that PI 3-kinase is likely to be an important mediator of some IL-1 effects, providing docking sites for additional signalling molecules...
  76. pmc Interleukin-1 (IL-1) system gene expression in granulosa cells: kinetics during terminal preovulatory follicle maturation in the mare
    Alain Martoriati
    Reproduction Equine, Physiologie de la Reproduction et des Comportements, INRA UMR6073, 37380 Nouzilly, France
    Reprod Biol Endocrinol 1:42. 2003
    ..Cells were analysed by RT-PCR and follicular fluids were studied by gel electrophoresis and immunoblotting...
  77. pmc Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family
    Cecilia Garlanda
    Department of Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milan, Italy
    Proc Natl Acad Sci U S A 101:3522-6. 2004
    ..Thus, TIR8 represents a negative pathway of regulation of the IL-1 receptor/TLR system, expressed in epithelial cells and DC, crucial for tuning inflammation in the gastrointestinal tract...
  78. ncbi Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88
    Uzma Hasan
    Schering Plough Research Institute, Laboratory for Immunological Research, Dardilly, France
    J Immunol 174:2942-50. 2005
    ..However, a complete TLR10 sequence could be detected in the rat genome, indicating that a functional copy may be preserved in this species...
  79. ncbi Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88
    Aisling Dunne
    Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland
    J Biol Chem 278:41443-51. 2003
    ..Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways...
  80. ncbi HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway
    Ramunas M Vabulas
    Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Trogerstrasse 9, Munich 81675, Germany
    J Biol Chem 277:15107-12. 2002
    ....
  81. ncbi Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and Solution Oriented Research for Science and Technology, Japan Science and Technology Corporation, Suita, Osaka, Japan
    J Immunol 169:6668-72. 2002
    ..TRIF associated with TLR3 and IFN regulatory factor 3. These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway...
  82. ncbi IL-1 and IL-18 receptors, and their extended family
    John E Sims
    Immunex Corporation, 51 University Street, Seattle, WA 98101, USA
    Curr Opin Immunol 14:117-22. 2002
    ..Moreover, it has become apparent that they are members of a larger family of related receptors, some of which can also be shown to contribute to host defense...
  83. ncbi Differential involvement of BB loops of toll-IL-1 resistance (TIR) domain-containing adapter proteins in TLR4- versus TLR2-mediated signal transduction
    Vladimir U Toshchakov
    Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA
    J Immunol 175:494-500. 2005
    ..Our data suggest that the interactions required for a fully functional TLR4 signaling "platform" are disrupted by these BPs, and that the adapter BB loops may serve distinct roles in TLR4 and TLR2 signalosome assembly...
  84. ncbi The interleukin-1 family: 10 years of discovery
    C A Dinarello
    Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts
    FASEB J 8:1314-25. 1994
    ..Although IL-1 contributes to the pathogenesis of many diseases, a small amount appears to be needed to combat infection and initiate healing processes. This article highlights 10 years of discoveries on IL-1...
  85. ncbi Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound
    Maria Loiarro
    Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
    J Leukoc Biol 82:801-10. 2007
    ..Our results indicate that ST2825 blocks IL-1R/TLR signaling by interfering with MyD88 homodimerization and suggest that it may have therapeutic potential in treatment of chronic inflammatory diseases...
  86. ncbi The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation, and tumorigenesis
    Hui Xiao
    Department of Immunology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Immunity 26:461-75. 2007
    ..Taken together, our results indicate that epithelium-derived SIGIRR is critical in controlling the homeostasis and innate immune responses of the colon to enteric microflora...
  87. ncbi IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family
    H Wesche
    Tularik Inc, South San Francisco, California 94080, USA
    J Biol Chem 274:19403-10. 1999
    ..The discovery of IRAK-M adds another level of complexity to our understanding of signaling by members of the Toll/IL-1 receptor family...
  88. pmc Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation
    Dietrich B Conze
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell Biol 28:3538-47. 2008
    ..Thus, K63-linked polyubiquitination of proximal signaling proteins is a common mechanism used by diverse innate immune receptors for recruiting IKK and activating NF-kappaB...
  89. pmc Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice
    R Horai
    Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108 8639, Japan
    J Exp Med 191:313-20. 2000
    ..Possible involvement of IL-1ra gene deficiency in RA will be discussed...
  90. ncbi Unique pattern of expression and inhibition of IL-1 signaling by the IL-1 receptor family member TIR8/SIGIRR
    Nadia Polentarutti
    Dept Immunology and Cell Biology, Mario Negri Institute for Pharmacological Research, Milan, 20157, Italy
    Eur Cytokine Netw 14:211-8. 2003
    ..Thus, TIR8 is a unique member of the IL-1R family, with a distinct pattern of epithelial expression, including the kidney and mucosae, and an inhibitory function on IL-1 signaling...
  91. ncbi Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase
    J A Thomas
    Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235, USA
    J Immunol 163:978-84. 1999
    ..These results demonstrate that although IRAK participates in IL-1 and IL-18 signal transduction, residual cytokine responsiveness operates through an IRAK-independent pathway...
  92. ncbi Crystal structure of the Toll/interleukin-1 receptor domain of human IL-1RAPL
    Javed A Khan
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    J Biol Chem 279:31664-70. 2004
    ..Deletion mutagenesis studies show that the activation of JNK by IL-1RAPL does not depend on the integrity of its TIR domain, suggesting a distinct mechanism of signaling through this receptor...
  93. ncbi Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling
    Christian Kollewe
    Department of Pharmacology, Hannover Medical School, D 30623 Hannover, Germany
    J Biol Chem 279:5227-36. 2004
    ..Thus, IRAK-1 regulates its own availability as an adapter molecule by sequential autophosphorylation...
  94. ncbi IRAK: a kinase associated with the interleukin-1 receptor
    Z Cao
    Molecular Biology Department, Tularik, Incorporated, South San Francisco, CA 94080, USA
    Science 271:1128-31. 1996
    ..The primary amino acid sequence of IRAK shares similarity with that of Pelle, a protein kinase that is essential for the activation of a NF-kappa B homolog in Drosophila...
  95. ncbi SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms
    Jinzhong Qin
    Department of Immunology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 280:25233-41. 2005
    ..These results indicate that SIGIRR inhibits IL-1 and LPS signaling pathways through differential mechanisms...
  96. ncbi The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense
    Aisling Dunne
    Department of Biochemistry and Biotechnology Institute, Trinity College, Dublin, Ireland
    Sci STKE 2003:re3. 2003
    ..This receptor superfamily, therefore, represents an ancient signaling system that is a critical determinant of the innate immune and inflammatory responses...
  97. ncbi Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family
    Michael U Martin
    Institute of Pharmacology OE 5320, Hannover Medical School, Germany
    Biochim Biophys Acta 1592:265-80. 2002
    ..The creation of pathogen-specific mediator environments by dendritic cells defines whether a cellular or humoral response will be activated in response to the pathogen...
  98. ncbi TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology
    Hao Wu
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Bioessays 25:1096-105. 2003
    ..By virtue of its many signaling roles, TRAF6 represents an important target in the regulation of many disease processes, including immunity, inflammation and osteoporosis...
  99. ncbi The Toll-IL-1 receptor adaptor family grows to five members
    Luke A J O'Neill
    Cytokine Research Group, Department of Biochemistry, Trinity College, Dublin, Ireland
    Trends Immunol 24:286-90. 2003
    ..It is probable that differential use of adaptors will help explain the distinct pathways activated by TLRs during host defence...
  100. pmc IL-1 mediates TNF-induced osteoclastogenesis
    Shi Wei
    Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 115:282-90. 2005
    ..Thus, IL-1 mediates the osteoclastogenic effect of TNF by enhancing stromal cell expression of RANKL and directly stimulating differentiation of osteoclast precursors...
  101. ncbi Phenotypic and functional characterization of mice that lack the type I receptor for IL-1
    M B Glaccum
    Immunex Corporation, Seattle, WA 98101, USA
    J Immunol 159:3364-71. 1997
    ..Interestingly, ICE-/-/type I IL-1R-/- double mutant mice are resistant to high dose LPS. Type I IL-1R-/- mice backcrossed to the C57BL/6 background were as equally resistant as wild-type mice to Listeria monocytogenes...

Research Grants63

  1. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ....
  2. Growth Factor and Antiapoptotic Gene Delivery to Human Islets
    Ram I Mahato; Fiscal Year: 2012
    ..This will decrease the number of islets required to achieve normoglycemia in type I diabetic patients. ..
  3. Impact of Exercise on Body Composition in Premature Infants: New Approaches
    Dan M Cooper; Fiscal Year: 2013
    ..Should the positive effects of augmented exercise on body composition be supported, we would then anticipate widespread benefit in preventing long-term health consequences of prematurity at relatively low cost. ..
  4. Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease
    Talat Alp Ikizler; Fiscal Year: 2013
    ..abstract_text> ..
  5. Biomarker of Tissue Tolerance and Behavior in a Rat Model of WMSD
    Mary F Barbe; Fiscal Year: 2013
    ..abstract_text> ..
  6. Anti-Inflammatory Interventions in Maintenance Hemodialysis Patients
    Talat Alp Ikizler; Fiscal Year: 2013
    ....
  7. Micro RNA-146a (miRNA-146a) signaling in Alzheimers disease (AD)
    Walter J Lukiw; Fiscal Year: 2013
    ....
  8. Role of the Prolyl Isomerase Pin1 in the Development and Treatment of Asthma
    Kun Ping Lu; Fiscal Year: 2013
    ..These studies would uncover a novel mechanism in asthma development, and also could lead to more effective therapies because Pin1 inhibitors, especially when inhaled, might inhibit multiple targets in different cells in asthma. ..
  9. Interleukin-33 and Myocardial Pressure Overload
    Richard T Lee; Fiscal Year: 2013
    ..This proposal addresses a newly-discovered signaling system in the heart that is activated by overloading the heart muscle. Understanding this signaling system could lead to new therapies for preventing heart failure. ..
  10. Role of the MyD88-independent pathway in Alzheimers disease
    Ken Ichiro Fukuchi; Fiscal Year: 2013
    ..The long term goals of this research are to determine the roles of TLR signaling in AD progression and to establish the logical basis for developing safe and effective immunotherapy for AD. ..
  11. Post-transcriptional control of inflammatory gene expression
    Thomas A Hamilton; Fiscal Year: 2013
    ..This proposal is focused upon understanding the mechanisms through which IL-17 (and other stimuli) controls degradation of specific inflammation related messenger RNAs and thereby modulates aspects of inflammatory response. ..
  12. Longitudinal Population-Based Study of Vulvodynia
    Barbara D Reed; Fiscal Year: 2012
    ....
  13. Genetic &immunologic etiology of chronic recurrent multifocal osteomyelitis-CRMO
    Polly J Ferguson; Fiscal Year: 2013
    ..Taken together, these assays will provide critical insights into the inflammatory pathways important in CRMO. ..
  14. The novel role and regulation of IRAK in innate immunity
    Liwu Li; Fiscal Year: 2010
    ..Aim2 will examine the mechanism for IRAK1 mediated IL-10 gene expression. Aim3 will study the effect of IRAK1 deletion on the pathogenesis and/or resolution of atherosclerosis. ..
  15. Function and Behavior Phenotype of Inflammatory Arthritis in the Rat Knee and TMJ
    Kyle D Allen; Fiscal Year: 2010
    ..Moreover, this research plan will assist the PI in transitioning to a faculty position and establish an independent research program evaluating therapeutic interventions for TMJ disorders and degeneration. ..
  16. RESOLUTION OF CLINICAL LUNG INJURY
    Michael A Matthay; Fiscal Year: 2013
    ..abstract_text> ..
  17. Structural and functional studies of the IkappaB kinase (IKK) complex
    Hao Wu; Fiscal Year: 2013
    ..In addition, the proposed studies will provide a structural basis for discovery and optimization of IKK inhibitors in the treatment of inflammatory diseases and cancer. ..
  18. Lung Fluid Balance and Mesenchymal Stem Cells
    Michael A Matthay; Fiscal Year: 2012
    ....
  19. Role of TRIF-dependent TLR signaling in intestinal immunity
    Masayuki Fukata; Fiscal Year: 2013
    ..Targeting TRIF is advantageous because a clinically tested TLR3 ligand is available. ..
  20. Role of TRIF-dependent TLR signaling in intestinal immunity
    Masayuki Fukata; Fiscal Year: 2011
    ..Targeting TRIF is advantageous because clinically approved TLR3 ligand is available. ..
  21. Gene Therapy for Cartilage Injury
    Alicia Bertone; Fiscal Year: 2009
    ..These genes, separately and in concert may significantly improve our current therapy options to the management of joint injury. ..
  22. Modulation of the Immune System to Improve Ligament/Ligament Graft Healing
    Ray Vanderby; Fiscal Year: 2013
    ..Each one of these would be of great significance and each would have much broader applications than those explored herein. ..
  23. Toll-like Receptors and Innate Immune Activation in Alzheimer's Disease
    BRENT DAVID CAMERON; Fiscal Year: 2013
    ..This project addresses the role that the immune system plays in Alzheimer's disease. A better understanding of the immune response in Alzheimer's disease will lead to more effective treatments. ..
  24. IL-1R1 promoter complex in the neuroendocrine, nervous, and immune systems
    Ning Quan; Fiscal Year: 2012
    ..The results will provide a foundation for the understanding of how dysregulation of the expression of type 1 interleukin-1 receptor may be involved in the pathogenesis of diseases in multiple systems. ..
  25. CYTOKINE REGULATION OF UTERINE OXYTOCIN RECEPTOR
    PHILLIP RAUK; Fiscal Year: 2001
    ..The antagonism of IL-1 by IL-lra and TGF beta will be studied. A detailed understanding of the regulation of uterine oxytocin receptors will increase the overall understanding of mechanisms of labor. ..
  26. PRESERVATION AND CARDIAC TRANSPLANT VASCULOPATHY
    David Pinsky; Fiscal Year: 2003
    ..These experiments will provide new insights into mechanisms by which early ischemic injury leads to early graft failure and TCAD, and proffer new strategies for prevention. ..
  27. HISTAMINE, IL-1 & NITRIC OXIDE IN WERNICKE LESIONS
    PHILIP LANGLAIS; Fiscal Year: 2002
    ..v.); and iv) mutant, mast cell deficient (Ws/Ws) rats. Quantitative measures of early vascular changes will be performed after 10 days and measures of late neurodegenerative changes performed after 15 days of treatment. ..
  28. INTRA-ARTICULAR DELIVERY OF PEPTIDES AND PROTEINS
    Paul Simpson; Fiscal Year: 1999
    ..This provides the opportunity for improving therapeutic outcomes and reducing costs during rehabilitation following surgery. ..
  29. Genome-wide profiling of immune responsiveness in patients with primary immunodef
    Damien Chaussabel; Fiscal Year: 2011
    ..Altogether this project will serve as a foundation for the development of novel tools to screen for and characterize primary immune deficiencies. ..
  30. ADRENAL REGENERATION-- IMMUNO-ENDOCRINE INTERACTIONS
    WILLIAM ENGELAND; Fiscal Year: 2003
    ....
  31. Gene Polymorphisms, Preterm Birth, Neonatal Complicatio*
    Steven Witkin; Fiscal Year: 2005
    ..Identification of genetic factors in mothers or their neonates that influence susceptibility to preterm labor and fetal morbidity in different racial groups will aid in development of improved protocols for monitoring and treatment...
  32. Regulation of signaling events in septic leukocytes
    Liwu Li; Fiscal Year: 2006
    ..We plan to identify the specific catalytic subunit(s) of PI3 kinase that is (are) activated by LPS, and responsible for elevated sIL-1RA translation. The mechanism of PI3 kinase enhanced translation will be studied. ..
  33. Role of the T1/ST2 receptor in myocardial ischemia/repe*
    ELLEN WEINBERG; Fiscal Year: 2004
    ..In specific aim 4 we propose to identify peptide ligands of T1/ST2 and their effects on the myocardium during ischemia and reperfusion. ..
  34. REGULATION OF CELL ACTIVATION BY FATTY ACIDS
    ROBERT ZURIER; Fiscal Year: 2000
    ..Results of these studies may lead to more rational use of fatty acids in the treatment of diseases characterized by disordered immune responses, acute and chronic inflammation, and tissue injury. ..
  35. VIRAL INHIBITION OF HOST DEFENSES
    DAVID PICKUP; Fiscal Year: 2000
    ....
  36. IL-1 RECEPTORS AND CUTANEOUS DISEASE
    Thomas Kupper; Fiscal Year: 2003
    ..Recognition of antigen in skin by recruited T cells leads to T cell cytokine production, and, ultimately, elimination of the pathogen. ..
  37. Structural biology of Toll like receptor/IL 1R signaling
    Liang Tong; Fiscal Year: 2005
    ..These will form the basis for further mutagenesis, biochemical, and functional studies to assess their importance. ..
  38. Are the effects of SIMPL on hematopoiesis seen in vitro translated in vivo?
    Maureen Harrington; Fiscal Year: 2009
    ..Identifying a role for SIMPL in the maintenance of hematopoietic stem cells will equip the applicant with the experimental skills to direct independent research addressing experimental hematopoiesis questions using whole animals. ..
  39. Cytokines Stimulate Prostate Epithelial Proliferation
    Wade Bushman; Fiscal Year: 2009
    ....
  40. Sleep Studies in HIV+ Older Children/Adolescents
    William Shearer; Fiscal Year: 2007
    ....
  41. BMI, Nutrition, Inflammation and Heart Failure Outcomes
    Terry Lennie; Fiscal Year: 2007
    ..An understanding of the underlying mechanisms may also allow application of these findings to underweight patients resulting in improved outcomes for these patients. ..
  42. VIRAL INHIBITION OF HOST DEFENSES
    DAVID PICKUP; Fiscal Year: 1999
    ....
  43. Polymorphic Cytokine Responses to Inflammation
    Terri Simpson; Fiscal Year: 2005
    ..abstract_text> ..
  44. DELIVERY OF THERAPEUTIC GENES TO HUMAN RHEUMATOID JOINTS
    Christopher Evans; Fiscal Year: 2000
    ..Safety monitoring of the patients will continue annually for life, as required by the FDA. ..
  45. IDENTIFICATION OF LPS-INDUCED SIGNALLING MECHAMISMS
    Michael Smith; Fiscal Year: 1999
    ..It is expected that these studies will provide significant new insights into the mechanisms through which LPS acts to regulate gene expression in monocytes and macrophages. ..
  46. IRAK Family Function in Bacterial Infection
    James Thomas; Fiscal Year: 2001
    ....
  47. BIOCOMPATIBILITY AND HEMODIALYSIS
    Brian Pereira; Fiscal Year: 2001
    ..The results of these studies are expected to shed light on the cause for the high morbidity and mortality in ESRD and ARF, and mechanisms behind the interventions to improve clinical outcomes. ..
  48. IN VIVO FUNCTION OF INTERLEUKIN 1 RECEPTOR ANTAGONIST
    David Hirsh; Fiscal Year: 2002
    ....
  49. CHARACTERIZATION OF INTERLEUKIN-1 RECEPTORS
    Janet Plate; Fiscal Year: 1990
    ..Alternatively, one may be able to find alternate means to signal IL-1 receptors in immune deficiency states such that helper T cell responses could be initiated...
  50. POSITIONAL CANDIDATE GENES FOR AIRWAY RESPONSIVENESS
    Susan Ewart; Fiscal Year: 2004
    ..The results of these studies may lead to better prevention and treatment of asthma. ..
  51. MECHANISMS OF GH RESISTANCE IN SEPSIS
    Robert Cooney; Fiscal Year: 2001
    ..These studies will reveal the molecular mechanisms by which IL-1ra ameliorates the development of GH resistance in sepsis. ..
  52. Cerebrovascular Atherosclerosis: Genes & Gene Expression
    BRADFORD WORRALL; Fiscal Year: 2009
    ....
  53. IL-1 Beta influences on NGF in neural Development
    ANNA JELASO; Fiscal Year: 2003
    ..This work will establish a system for understanding how cytokines and neurotrophins interact during neural development to influence the development and/or maintenance of functional neural circuits. ..
  54. Novel Nanostructured Calcium Phosphate for Gene Delivery to Bone
    Christopher Evans; Fiscal Year: 2005
    ..2. To evaluate the ability of nCaP-vector constructs to enhance osteogenic responses in vivo. ..
  55. AAOS/NIH Mulit-Year Research Symposia for 2005-2009
    Christopher Evans; Fiscal Year: 2005
    ....
  56. Lanthanides as Novel Anti-Arthritic Agents
    Christopher Evans; Fiscal Year: 2004
    ..A successful outcome to these studies will have identified the basis for a potential new, very inexpensive anti-rheumatic agent whose mode of action differs from that of existing drugs. ..
  57. Delivery of Therapeutic Genes to Osteoarthritic Joints
    Christopher Evans; Fiscal Year: 2002
    ....
  58. IL1 RECEPTOR ANTAGONIST INTRACELLULAR VARIANTS
    WILLIAM AREND; Fiscal Year: 2003
    ..Not only does sIL-1Ra inhibit the binding of IL-1 to cell surface receptors, but they hypothesize that the intracellular isoforms of IL-1Ra will exhibit additional antiinflammatory effect inside cells. ..
  59. Molecular Mechanisms for IL-25-mediated Th2 Responses
    Xiaoxia Li; Fiscal Year: 2010
    ..With this improved understanding comes the potential to develop specific inhibitors of these pathways and perhaps novel therapeutics for the treatment of asthma. ..
  60. Act1 in CD40-/BAFFR-Mediated B Cell Survival
    Xiaoxia Li; Fiscal Year: 2009
    ..These findings will help us to elucidate the detailed regulatory mechanism for B cell homeostasis and opens new possibility to intervene the immune system. ..
  61. SIGIRR A Negative Regulator of Toll-IL-IR Signaling
    Xiaoxia Li; Fiscal Year: 2009
    ..Specifically, the proposed studies should result in significant advances in the field of innate mucosal immunity and should also help us to determine the potential of SIGIRR as a target for developing anti-inflammatory drugs. ..