tumor necrosis factor receptors

Summary

Summary: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.

Top Publications

  1. ncbi Targeting death and decoy receptors of the tumour-necrosis factor superfamily
    Avi Ashkenazi
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Rev Cancer 2:420-30. 2002
  2. ncbi Osteoprotegerin: a novel secreted protein involved in the regulation of bone density
    W S Simonet
    Department of Molecular Genetics, Amgen Inc, Thousand Oaks, California 91320, USA
    Cell 89:309-19. 1997
  3. pmc Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, 519 Ishibashi machi, Shimotsuga gun, Tochigi 329 0512, Japan
    Proc Natl Acad Sci U S A 95:3597-602. 1998
  4. ncbi The receptor for the cytotoxic ligand TRAIL
    G Pan
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 276:111-3. 1997
  5. pmc osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
    N Bucay
    Department of Molecular Genetics, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Genes Dev 12:1260-8. 1998
  6. ncbi A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function
    D M Anderson
    Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101, USA
    Nature 390:175-9. 1997
  7. ncbi Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
    Olivier Micheau
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Cell 114:181-90. 2003
  8. ncbi Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand
    Y Y Kong
    Amgen Institute, Toronto, Ontario, Canada
    Nature 402:304-9. 1999
  9. pmc Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand
    H Hsu
    Department of Cell Biology, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
    Proc Natl Acad Sci U S A 96:3540-5. 1999
  10. ncbi Apoptosis by death factor
    S Nagata
    Department of Genetics, Osaka University Medical School, Japan
    Cell 88:355-65. 1997

Detail Information

Publications275 found, 100 shown here

  1. ncbi Targeting death and decoy receptors of the tumour-necrosis factor superfamily
    Avi Ashkenazi
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nat Rev Cancer 2:420-30. 2002
  2. ncbi Osteoprotegerin: a novel secreted protein involved in the regulation of bone density
    W S Simonet
    Department of Molecular Genetics, Amgen Inc, Thousand Oaks, California 91320, USA
    Cell 89:309-19. 1997
    ..These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity...
  3. pmc Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, 519 Ishibashi machi, Shimotsuga gun, Tochigi 329 0512, Japan
    Proc Natl Acad Sci U S A 95:3597-602. 1998
    ..ODF was found to be identical to TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function. ODF seems to be an important regulator in not only osteoclastogenesis but also immune system...
  4. ncbi The receptor for the cytotoxic ligand TRAIL
    G Pan
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 276:111-3. 1997
    ..Thus, the DR4-TRAIL axis defines another receptor-ligand pair involved in regulating cell suicide and tissue homeostasis...
  5. pmc osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
    N Bucay
    Department of Molecular Genetics, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Genes Dev 12:1260-8. 1998
    ....
  6. ncbi A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function
    D M Anderson
    Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101, USA
    Nature 390:175-9. 1997
    ..Thus RANK and RANKL seem to be important regulators of interactions between T cells and dendritic cells...
  7. ncbi Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
    Olivier Micheau
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Cell 114:181-90. 2003
    ..Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated...
  8. ncbi Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand
    Y Y Kong
    Amgen Institute, Toronto, Ontario, Canada
    Nature 402:304-9. 1999
    ..These results show that both systemic and local T-cell activation can lead to OPGL production and subsequent bone loss, and they provide a novel paradigm for T cells as regulators of bone physiology...
  9. pmc Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand
    H Hsu
    Department of Cell Biology, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
    Proc Natl Acad Sci U S A 96:3540-5. 1999
    ..These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells...
  10. ncbi Apoptosis by death factor
    S Nagata
    Department of Genetics, Osaka University Medical School, Japan
    Cell 88:355-65. 1997
  11. ncbi Death receptors: signaling and modulation
    A Ashkenazi
    Department of Molecular Oncology, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Science 281:1305-8. 1998
    ..Certain cells have unique sensors, termed death receptors, on their surface. Death receptors detect the presence of extracellular death signals and, in response, they rapidly ignite the cell's intrinsic apoptosis machinery...
  12. ncbi The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor
    B R Wong
    Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 273:28355-9. 1998
    ..Furthermore, transfection experiments with TRANCE-R deletion mutants revealed that multiple regions of the TRANCE-R can mediate NF-kappaB activation...
  13. ncbi An antagonist decoy receptor and a death domain-containing receptor for TRAIL
    G Pan
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
    Science 277:815-8. 1997
    ..Another death domain-containing receptor for TRAIL (designated as death receptor-5), which preferentially engaged a FLICE (caspase-8)-related death protease, was also identified...
  14. ncbi Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors
    J P Sheridan
    Department of Molecular Oncology, Genentech, South San Francisco, CA 94080 4918, USA
    Science 277:818-21. 1997
    ..DcR1 acted as a decoy receptor that inhibited TRAIL signaling. Thus, a cell surface mechanism exists for the regulation of cellular responsiveness to pro-apoptotic stimuli...
  15. ncbi FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2
    M R Sprick
    Tumor Immunology Program, German Cancer Research Center DKFZ Heidelberg
    Immunity 12:599-609. 2000
    ..FADD/MORT1- and caspase-8-deficient Jurkat cells expressing only TRAIL-R2 were resistant to TRAIL-induced apoptosis. Thus, FADD/MORT1 and caspase-8 are essential for apoptosis induction via TRAIL-R2...
  16. pmc RANK is essential for osteoclast and lymph node development
    W C Dougall
    Immunex Corporation, Seattle, Washington 98101 USA
    Genes Dev 13:2412-24. 1999
    ..These experiments reveal that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation...
  17. ncbi Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro
    H Yasuda
    Research Institute of Life Science, Snow Brand Milk Products Co, Ltd, Tochigi, Japan
    Endocrinology 139:1329-37. 1998
    ..These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites...
  18. ncbi Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway
    P M Chaudhary
    Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA
    Immunity 7:821-30. 1997
    ..Thus, both DR5 and DR4 use FADD, TRADD, and RIP in their signal transduction pathways, and FADD is the common mediator of apoptosis by all known death domain-containing receptors...
  19. ncbi Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?
    M Feldmann
    Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 1 Aspenlea Road, London W6 8LH, United Kingdom
    Annu Rev Immunol 19:163-96. 2001
    ..Infliximab (a mAB), and etanercept (a sTNF-R-Fc fusion protein) have been approved by regulatory authorities in the United States and Europe for treating RA, and they represent a significant new addition to available therapeutic options...
  20. ncbi OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells
    P R Rogers
    Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    Immunity 15:445-55. 2001
    ..Moreover, retroviral transduction of OX40-/- T cells with Bcl-xL or Bcl-2 reverses their survival defect. Thus, a temporal relationship exists between CD28 and OX40, with OX40 being a critical regulator of antigen-driven T cell survival...
  21. ncbi Synaptic scaling mediated by glial TNF-alpha
    David Stellwagen
    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 94304 5485, USA
    Nature 440:1054-9. 2006
    ..We suggest that by modulating TNF-alpha levels, glia actively participate in the homeostatic activity-dependent regulation of synaptic connectivity...
  22. ncbi The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain
    M A Degli-Esposti
    Department of Biochemistry, Immunex Corporation, Seattle, Washington 98101, USA
    Immunity 7:813-20. 1997
    ..Like TRAIL-R1 and TRAIL-R2, this receptor shows widespread tissue expression. The human TRAIL-R4 gene has been mapped to chromosome 8p22-21, clustered with three other TRAIL receptors...
  23. ncbi The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins
    M Rothe
    Department of Molecular Biology Tularik, Incorporated, South San Francisco, California 94080, USA
    Cell 83:1243-52. 1995
    ..The recruitment of c-IAP1 or c-IAP2 to the TNFR2 signaling complex requires a TRAF2-TRAF1 heterocomplex...
  24. ncbi TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways
    H Hsu
    Tularik, Incorporated, South San Francisco, California 94080, USA
    Cell 84:299-308. 1996
    ..Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD...
  25. ncbi Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB
    R Ravi
    Johns Hopkins Oncology Center, The Johns Hopkins University School of Medicine, Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, Maryland 21231, USA
    Nat Cell Biol 3:409-16. 2001
    ..The ability to induce death receptors or Bcl-xL may explain the dual roles of NF-kappaB as a mediator or inhibitor of cell death during immune and stress responses...
  26. ncbi The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation
    H Hsu
    Tularik, Incorporated, South San Francisco, California 94080, USA
    Cell 81:495-504. 1995
    ..However, NF-kappa B activation by TRADD is not inhibited by crmA expression, demonstrating that the signaling pathways for TNF-induced cell death and NF-kappa B activation are distinct...
  27. ncbi Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance
    Jun Shimizu
    Department of Immunopathology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173 0015, Japan
    Nat Immunol 3:135-42. 2002
    ..Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease...
  28. ncbi Control of synaptic strength by glial TNFalpha
    Eric C Beattie
    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA
    Science 295:2282-5. 2002
    ..Through its effects on AMPA receptor trafficking, TNFalpha may play roles in synaptic plasticity and modulating responses to neural injury...
  29. ncbi BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator
    P A Moore
    Human Genome Sciences, 9410 Key West Avenue, Rockville, MD 20850, USA
    Science 285:260-3. 1999
    ..The B cell tropism of BLyS is consistent with its receptor expression on B-lineage cells. The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation...
  30. ncbi Receptor-selective mutants of apoptosis-inducing ligand 2/tumor necrosis factor-related apoptosis-inducing ligand reveal a greater contribution of death receptor (DR) 5 than DR4 to apoptosis signaling
    Robert F Kelley
    Department of Protein Engineering, Genentech, Inc, South San Francisco, California 94080, USA
    J Biol Chem 280:2205-12. 2005
    ..These results suggest that DR5 may contribute more than DR4 to Apo2L/TRAIL-induced apoptosis in cancer cells that express both death receptors...
  31. ncbi The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion
    I Gramaglia
    Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    J Immunol 165:3043-50. 2000
    ..In this way, OX40 signals promote survival of greater numbers of T cells with time and control the size of the memory T cell pool...
  32. ncbi Tumor necrosis factor signaling
    H Wajant
    Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring, Germany
    Cell Death Differ 10:45-65. 2003
    ..In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed...
  33. ncbi Osteoclast differentiation and activation
    William J Boyle
    Protein Pathways, Inc, Woodland Hills, California 91367, USA
    Nature 423:337-42. 2003
    ..Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss...
  34. ncbi Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation
    D L Lacey
    Department of Pathology, Amgen, Inc, Thousand Oaks, California 91320 1789, USA
    Cell 93:165-76. 1998
    ..These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development...
  35. ncbi The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family
    G Mosialos
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    Cell 80:389-99. 1995
    ..The interaction of LMP1 with these TNFR family-associated proteins is further evidence for their role in signaling and links LMP1-mediated transformation to signal transduction from the TNFR family...
  36. ncbi An essential role for Scurfin in CD4+CD25+ T regulatory cells
    Roli Khattri
    Celltech R and D Inc, 1631 220th Street SE, Bothell, Washington 98021, USA
    Nat Immunol 4:337-42. 2003
    ..The forced expression of Foxp3 also delays disease in CTLA-4-/- mice, indicating that the Scurfin and CTLA-4 pathways may intersect and providing further insight into the T(R) cell lineage...
  37. ncbi Granulomatous infectious diseases associated with tumor necrosis factor antagonists
    R S Wallis
    Department of Medicine, University of Medicine and Dentistry of New Jersey New Jersey Medical School, Newark, NJ 07103, USA
    Clin Infect Dis 38:1261-5. 2004
    ..25-fold greater among patients who received infliximab than among those who received etanercept. The clustering of reports shortly after initiation of treatment with infliximab is consistent with reactivation of latent infection...
  38. pmc BCMA is essential for the survival of long-lived bone marrow plasma cells
    BRIAN P O'CONNOR
    Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA
    J Exp Med 199:91-8. 2004
    ..These findings offer new insights into the molecular basis for the long-term survival of PCs...
  39. ncbi A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis
    S R Wiley
    Immunex Corporation, 51 University Street, Seattle, WA 98101, USA
    Immunity 15:837-46. 2001
    ..Soluble TweakR inhibits endothelial cell migration in vitro and corneal angiogenesis in vivo...
  40. ncbi TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells
    B R Wong
    The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 272:25190-4. 1997
    ..These results suggest a role for this TNF-related ligand in the regulation of the T cell-dependent immune response...
  41. ncbi Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice
    J L Flynn
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA
    Immunity 2:561-72. 1995
    ..TNF alpha and the 55 kDa TNF receptor are necessary conditions for protection against murine M. tuberculosis infection, but are not solely responsible for the tissue damage observed...
  42. ncbi Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes
    M F McDermott
    Medical Unit, St Bartholomew s and The Royal London Hospital School of Medicine and Dentistry, Whitechapel, London, England
    Cell 97:133-44. 1999
    ..TNFR1-associated periodic syndromes (TRAPS) establish an important class of mutations in TNF receptors. Detailed analysis of one such mutation suggests impaired cytokine receptor clearance as a novel mechanism of disease...
  43. ncbi An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway
    B Schiemann
    Biogen, 14 Cambridge Center, Cambridge, MA 02142, USA
    Science 293:2111-4. 2001
    ..In contrast, mice lacking BCMA had normal-appearing B lymphocyte compartments. BAFF therefore plays a crucial role in B cell development and can function through receptors other than BCMA...
  44. ncbi GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations
    Simona Ronchetti
    Eur J Immunol 34:613-22. 2004
    ..These results indicate a novel function for GITR as costimulatory molecule of T cell subsets...
  45. pmc TRAIL/Apo-2L: mechanisms and clinical applications in cancer
    R K Srivastava
    Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy Greenebaum Cancer Center, 20 North Pine Street, Baltimore, MD 21201, USA
    Neoplasia 3:535-46. 2001
    ..Nontagged Apo-2L/TRAIL does not cause hepatotoxicity in monkeys and chimpanzees and in normal human hepatocytes. Thus, nontagged Apo-2L/TRAIL appears to be a promising new candidate for use in the treatment of cancer...
  46. ncbi Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial
    Lars Klareskog
    Rheumatology Unit, Department of Medicine, Karolinska Institute Karolinska Hospital, Stockholm 17176, Sweden
    Lancet 363:675-81. 2004
    ..We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis...
  47. ncbi Apo2L/TRAIL and its death and decoy receptors
    H N LeBlanc
    Department of Molecular Oncology, Genetech, Inc, South San Francisco, CA 94080, USA
    Cell Death Differ 10:66-75. 2003
    ..In this review, we focus on the apoptotic signalling pathways stimulated by Apo2L/TRAIL and summarise what is known about its physiological role...
  48. ncbi LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator
    D N Mauri
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    Immunity 8:21-30. 1998
    ..This characterizes herpesvirus gD as a membrane-bound viokine and establishes LIGHT-HVEM as integral components of the lymphotoxin cytokine-receptor system...
  49. ncbi Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family
    R I Montgomery
    Northwestern University Medical School, Department of Microbiology Immunology, Chicago, Illinois 60611, USA
    Cell 87:427-36. 1996
    ..The contribution of HVEM to HSV entry into human cells was demonstrable in activated T cells. HVEM, the first identified mediator of HSV entry, is a new member of the TNF/NGF receptor family...
  50. pmc BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth
    P Schneider
    Institute of Biochemistry, University of Lausanne, Switzerland
    J Exp Med 189:1747-56. 1999
    ..These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function...
  51. pmc The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor
    M Grell
    Institute of Cell Biology and Immunology, University of Stuttgart, Germany
    Proc Natl Acad Sci U S A 95:570-5. 1998
    ..In accordance with this reasoning, the lower signaling capability of homotrimeric lymphotoxin, compared with TNF, correlates with a lower stability of the lymphotoxin-TNF-R1 complex at 37 degrees C...
  52. ncbi Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum
    Juanita H Vernooy
    Nutrition and Toxicology Research Institute Maastricht, Department of Pulmonology, Maastricht University, The Netherlands
    Am J Respir Crit Care Med 166:1218-24. 2002
    ....
  53. ncbi Tumor necrosis factor receptor and Fas signaling mechanisms
    D Wallach
    Department of Biological Chemistry, Weizmann Institute, Rehovot, Israel
    Annu Rev Immunol 17:331-67. 1999
    ....
  54. pmc Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family
    M A Degli-Esposti
    Department of Biochemistry and the Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101, USA
    J Exp Med 186:1165-70. 1997
    ..Moreover, unlike TRAIL-R1 and -R2, in a transient overexpression system TRAIL-R3 does not induce apoptosis...
  55. ncbi Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses
    Mercedesz Balazs
    Division of Developmental and Clinical Immunology, Department of Microbiology, University of Alabama, Birmingham, AL 35294, USA
    Immunity 17:341-52. 2002
    ..In the absence of soluble TACI ligands, Ag-activated MZ- and B1-derived blasts lack survival signals and undergo apoptosis, resulting in severely impaired antibody responses...
  56. ncbi Apoptotic pathways: paper wraps stone blunts scissors
    D R Green
    La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
    Cell 102:1-4. 2000
  57. ncbi Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activation
    Daniel F Legler
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH 1066 Epalinges, Switzerland
    Immunity 18:655-64. 2003
    ..We suggest that lipid rafts are crucial for the outcome of TNFalpha-activated signaling pathways...
  58. ncbi TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor
    Steven R Wiley
    Amgen Corporation, Seattle, WA 98101, USA
    Cytokine Growth Factor Rev 14:241-9. 2003
    ..Although these studies have contributed a significant amount of new information, numerous questions still remain regarding the role of TWEAK in both normal physiology and the pathogenesis of human disease...
  59. pmc Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells
    Kuibeom Ko
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan
    J Exp Med 202:885-91. 2005
    ..Agonistic anti-GITR mAb is therefore instrumental in treating advanced cancers...
  60. ncbi Differential expression, cytokine modulation, and specific functions of type-1 and type-2 tumor necrosis factor receptors in rat glia
    J M Dopp
    Department of Neurology, UCLA 90095, USA
    J Neuroimmunol 75:104-12. 1997
    ..Different patterns of TNFR expression by glia at sites of CNS inflammation may be critical in determining whether TNF has activational, proliferative, or cytotoxic effects on these cells...
  61. ncbi Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families
    T Suda
    Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
    Endocr Rev 20:345-57. 1999
    ....
  62. ncbi TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40
    M Rothe
    Molecular Biology Department, Tularik, Inc, South San Francisco, CA 94080, USA
    Science 269:1424-7. 1995
    ..A truncated derivative of TRAF2 lacking an amino-terminal RING finger domain was a dominant-negative inhibitor of NF-kappa B activation mediated by TNF-R2 and CD40. Thus, TRAF2 is a common mediator of TNF-R2 and CD40 signaling...
  63. ncbi TWEAK attenuates the transition from innate to adaptive immunity
    Heather Maecker
    Department of Molecular Oncology, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell 123:931-44. 2005
    ..Thus, TWEAK suppresses production of IFN-gamma and IL-12, curtailing the innate response and its transition to adaptive TH1 immunity...
  64. ncbi Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy
    Alexandru Almasan
    Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Cytokine Growth Factor Rev 14:337-48. 2003
    ..In this review, we focus on the apoptosis signaling pathways stimulated by Apo2L/TRAIL, summarize what is known to date about the physiological role of this ligand and the potential for its application to cancer therapy...
  65. ncbi Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels
    R Nimmanapalli
    Moffitt Cancer Center and Research Institute, University of South Florida, Tampa 33612, USA
    Cancer Res 61:759-63. 2001
    ..These findings indicate that up-regulation of DR4 and DR5 protein levels by treatment with paclitaxel enhances subsequent Apo-2L/TRAIL-induced apoptosis of human prostate cancer cells...
  66. pmc Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis
    Y Lin
    Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genes Dev 13:2514-26. 1999
    ..Further more, RIP cleavage was also detected in other death receptor-mediated apoptosis. Therefore, our study provides a potential mechanism to convert cells from life to death in death receptor-mediated apoptosis...
  67. ncbi An essential role for NF-kappaB in preventing TNF-alpha-induced cell death
    A A Beg
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 274:782-4. 1996
    ..These results have implications for the treatment of inflammatory and proliferative diseases...
  68. ncbi Expression and function of OX40 ligand on human dendritic cells
    Y Ohshima
    University of Montreal, Centre de Recherche Louis Charles Simard, Notre Dame Hospital, Quebec, Canada
    J Immunol 159:3838-48. 1997
    ..Thus, the expression of OX40L on DC suggests a physiologic role of this molecule during T cell priming by virtue of its ability to costimulate both T cell and DC activation and differentiation...
  69. ncbi Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG(35-55)-induced experimental autoimmune encephalomyelitis
    G C Suvannavejh
    Department of Microbiology Immunology, Interdepartmental Immunology Center, Northwestern University Medical School, 303 E Chicago Avenue, Illinois 60611, USA
    Cell Immunol 205:24-33. 2000
    ..These results have important implications for therapies targeting p55 and p75 receptors for treating autoimmune diseases...
  70. pmc A regulatory role for TRAF1 in antigen-induced apoptosis of T cells
    D E Speiser
    Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, Toronto, Ontario M5G 2M9, Canada
    J Exp Med 185:1777-83. 1997
    ....
  71. pmc TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL
    H Walczak
    Immunex Corporation, 51 University Street, Seattle, WA 98101, USA
    EMBO J 16:5386-97. 1997
    ..The existence of two distinct receptors for the same ligand suggests an unexpected complexity to TRAIL biology, reminiscent of dual receptors for TNF, the canonical member of this family...
  72. pmc Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor
    Y Yamada
    Department of Pathology, University of Washington, Seattle 98195, USA
    Proc Natl Acad Sci U S A 94:1441-6. 1997
    ..The results indicate that TNF, signaling through the TNFR-I, can initiate liver regeneration and acts by activating an interleukin 6-dependent pathway that involves the STAT3 transcription factor...
  73. ncbi Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins
    M Takeuchi
    Yamanouchi Pharmaceutical Co Ltd, Tsukuba, Ibaraki 305, Japan
    J Biol Chem 271:19935-42. 1996
    ..Thus, distinct domains of TRAF2 are involved in recruitment and signaling functions...
  74. ncbi Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95
    A M Chinnaiyan
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA Sciences Inc, 9620 Medical Center Driv
    Science 274:990-2. 1996
    ..DR3 signal transduction is mediated by a complex of intracellular signaling molecules including TRADD, TRAF2, FADD, and FLICE. Thus, DR3 likely plays a role in regulating lymphocyte homeostasis...
  75. ncbi TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2
    Xiaoming Li
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nature 416:345-7. 2002
    ..These findings identify a physiologic role for c-IAP1 and define a mechanism by which TNF-RII-regulated ubiquitin protein ligase activity can potentiate TNF-induced apoptosis...
  76. ncbi Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8
    Mariola Fotin-Mleczek
    Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
    J Cell Sci 115:2757-70. 2002
    ..Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level...
  77. ncbi The promise of 4-1BB (CD137)-mediated immunomodulation and the immunotherapy of cancer
    David H Lynch
    Bainbridge Biopharma Consulting, Bainbridge Island, WA, USA
    Immunol Rev 222:277-86. 2008
    ..The results of the studies cited in this review highlight the potentials of 4-1BB-mediated immunotherapy...
  78. ncbi A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors
    Jong Bae Park
    Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Neuron 45:345-51. 2005
    ..Our results implicate TROY in mediating myelin inhibition, offering new insights into the molecular mechanisms of regeneration failure in the adult nervous system...
  79. ncbi TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex
    H Hsu
    Tularik, Incorporated, South San Francisco, California 94080, USA
    Immunity 4:387-96. 1996
    ..These results suggest that distinct domains of RIP participate in the TNF signaling cascades leading to apoptosis and NF-kappa B activation...
  80. pmc Tumor necrosis factor-alpha mediates orthopedic implant osteolysis
    K D Merkel
    Department of Orthopedic Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Am J Pathol 154:203-10. 1999
    ..Finally, the protective effect of deletion of both TNF receptors is recapitulated in mice lacking only the p55 receptor. Thus, targeting TNF and/or its p55 receptor may arrest wear particle osteolysis...
  81. ncbi A novel receptor for Apo2L/TRAIL contains a truncated death domain
    S A Marsters
    Department of Molecular Oncology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080 4918, USA
    Curr Biol 7:1003-6. 1997
    ..Upon overexpression, DcR2 did not activate apoptosis or nuclear factor-kappaB; however, it substantially reduced cellular sensitivity to Apo2L-induced apoptosis. These results suggest that DcR2 functions as an inhibitory Apo2L receptor...
  82. ncbi BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells
    Estefania Claudio
    Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1876, USA
    Nat Immunol 3:958-65. 2002
    ..This NEMO-independent cascade is physiologically relevant for the survival and, hence, progression of maturing splenic B cells...
  83. pmc A novel role for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the development of cardiac dysfunction and failure
    Mohit Jain
    Division of Cardiology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Circulation 119:2058-68. 2009
    ..Although many of the processes and downstream signals regulated by the TWEAK/Fn14 pathway have been implicated in the development of cardiac dysfunction, the role of TWEAK in the cardiovascular system is completely unknown...
  84. ncbi Anti-TNFalpha therapy in rheumatoid arthritis and autoimmunity
    Paola Caramaschi
    Dipartimento di Medicina Clinica e Sperimentale, Universita di Verona, Verona, Italy
    Rheumatol Int 26:209-14. 2006
    ..Both CRP and Blys do not seem to participate in this phenomenon. Other autoantibodies were detected in a few patients, but no case of onset of new autoimmune disorders was observed...
  85. ncbi TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation
    J J Peschon
    Department of Molecular Immunology, Immunex Corp, Seattle, WA 98101, USA
    J Immunol 160:943-52. 1998
    ..In summary, these data help clarify the biologic roles of p55 and p75 in mediating and modulating the biologic activity of TNF and provide genetic evidence for an antagonistic role of p75 in vivo...
  86. ncbi Neutralization of tumor necrosis factor (TNF) by antibody but not TNF receptor fusion molecule exacerbates chronic murine tuberculosis
    Hillarie L Plessner
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    J Infect Dis 195:1643-50. 2007
    ..These findings begin to clarify the mechanistic difference between anti-TNF agents and their role in the exacerbation of tuberculosis...
  87. ncbi Generation of highly suppressive adaptive CD8(+)CD25(+)FOXP3(+) regulatory T cells by continuous antigen stimulation
    Milada Mahic
    Biotechnology Centre and Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Norway
    Eur J Immunol 38:640-6. 2008
    ..However, neither blocking antibodies to CTLA-4, CD80 nor CD86 could reverse CD8(+) T(R)-mediated suppression, indicating that other mechanism(s) must be employed by these cells...
  88. ncbi TWEAK mediates signal transduction and differentiation of RAW264.7 cells in the absence of Fn14/TweakR. Evidence for a second TWEAK receptor
    Tara C Polek
    Department of Bioimmunotherapy, Section of Cytokine Research, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 278:32317-23. 2003
    ..We propose that the biological effects of TWEAK are mediated by binding to one of at least two distinct receptors that induce differential activation of downstream signaling pathways...
  89. ncbi CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor
    Rebecca S McHugh
    Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 16:311-23. 2002
    ..Importantly, antibodies to GITR abrogated suppression, demonstrating a functional role for this receptor in regulating the CD4(+)CD25(+) T cell subset...
  90. ncbi BAFF: a fundamental survival factor for B cells
    Fabienne Mackay
    Garvan Institute of Medical Research, Department of Arthritis and Inflammation, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia
    Nat Rev Immunol 2:465-75. 2002
    ..The elucidation of the role of BAFF has set the stage for a new approach to the treatment of autoimmune disease...
  91. pmc TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha
    James E Vince
    Department of Biochemistry, La Trobe University, Kingsbury Drive, Melbourne, VIC 3086, Australia
    J Cell Biol 182:171-84. 2008
    ..Lysosomal degradation of cIAP1-TRAF2 by TWEAK/FN14 therefore critically alters the balance of life/death signals emanating from TNF-R1 in immortalized cells...
  92. ncbi Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction
    Jagan R Muppidi
    Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 21:461-5. 2004
    ..Here, we discuss how receptor submembrane localization and the formation of alternate signaling complexes can alter the fate of cells stimulated through TNFRs with a death domain, also known as "death receptors."..
  93. pmc Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: the ADORE study
    P L C M van Riel
    Radboud University Nijmegen Medical Centre, Department of Rheumatology, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands
    Ann Rheum Dis 65:1478-83. 2006
    ..The response was defined by the presence of Disease Activity Score-28 joint count (DAS28) >or=3.2 or a combination of >or=5 swollen joints, >or=5 painful joints and erythrocyte sedimentation rate >or=10 mm/h.)..
  94. ncbi Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes
    Long Jin
    Atopy Allergy Research Center, Juntendo University School of Medicine, Tokyo, Japan
    J Invest Dermatol 122:1175-9. 2004
    ..Because RANTES has been implicated in inflammation, TWEAK/Fn14 interaction in human keratinocytes may be involved in the pathophysiology of inflammatory skin disorders...
  95. 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
    ..Thus, we can exclude RIP3 as an essential modulator of NF-kappa B signaling downstream of several receptor systems...
  96. ncbi The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
    David L Boone
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
    Nat Immunol 5:1052-60. 2004
    ..The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells...
  97. ncbi Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B
    I K Jang
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202 5120, USA
    Biochem Biophys Res Commun 242:613-20. 1998
    ..4-1BB-mediated NF-kappa B activation was inhibited by a dominant negative-TRAF2 or -NF-kappa B-inducing kinase (NIK). These data suggest that 4-1BB functions may be mediated by NF-kappa B activation, which requires a TRAF2/NIK pathway...
  98. ncbi B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells
    Lai Guan Ng
    Arthritis and Asthma Research Program, The Garvan Institute of Medical Research, Sydney, New South Wales, Australia
    J Immunol 173:807-17. 2004
    ..Thus, BAFF-R is important not only for splenic B cell maturation, but is the major mediator of BAFF-dependent costimulatory responses in peripheral B and T cells...
  99. ncbi Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif
    B G Darnay
    Cytokine Research Laboratory, Department of Molecular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 274:7724-31. 1999
    ....
  100. ncbi Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells
    Norihiro Harada
    Department of Immunology, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo, Japan
    Biochem Biophys Res Commun 299:488-93. 2002
    ..These results indicated that TWEAK could induce pro-inflammatory reactions via Fn14 on HUVEC...
  101. pmc CD4+CD25+ T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion
    Ann E Herman
    Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, MA 02215, USA
    J Exp Med 199:1479-89. 2004
    ..Thus, CD4+CD25+69- Tregs operate directly in the autoimmune lesion and are dependent on ICOS to keep it in a nondestructive state...

Research Grants73

  1. RANK-Associated Inhibitor (RAIN) in Osteoclast Formation
    Bryant Darnay; Fiscal Year: 2007
    ..abstract_text> ..
  2. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ....
  3. Mitochondrial Mechanisms of Programmed Necrosis in the Aged Female Heart
    Alexandra M Machikas; Fiscal Year: 2013
    ..The findings from this study will be invaluable in establishing the phenotype of cell death characteristic of I/R injury in the aged female heart and may supply clear evidence of the mitochondria as a therapeutic target for AMI. ..
  4. Regulation of Signaling Receptor Activity by LRP-1
    Steven L Gonias; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: Low density lipoprotein receptor-related protein has emerged as an important regulator of inflammation and atherosclerosis. This proposal seeks to elucidate the responsible mechanisms. ..
  5. TNF-Mediated Tumor Promotion: The Role of Vascular Leukocytes
    Pampee P Young; Fiscal Year: 2011
    ..Cancer continues to be a pervasive and prevalent health problem among our aging Veterans and critical to the biomedical research mission of the Veterans Affairs. ..
  6. Effect of constitutive Type 2 NF-kB on adipogenesis
    LOTUS KYI LOO; Fiscal Year: 2010
    ....
  7. DIETARY PATTERNS AND RISK OF CARDIOVASCULAR DISEASE
    Frank B Hu; Fiscal Year: 2013
    ....
  8. Heat Shock-Induced Apoptosis
    Shawn B Bratton; Fiscal Year: 2012
    ..Thus, it is anticipated that the work proposed herein will significantly improve our understanding of how heat shock works in the clinic and may shed light on new pathways that can be exploited therapeutically in the future. ..
  9. Tc-99m-Labled Cytokine Ligands and SPECT Inflammation Imaging of Ischemic Hearts
    Zhonglin Liu; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Development of highly specific imaging agents for noninvasive detection of inflammation induced by heart attacks. ..
  10. TNRF1 Signaling Resistance in Ischemic Human Female Myocardium
    Daniel R Meldrum; Fiscal Year: 2010
    ..Female and male myocardium from the following study subjects will be tested: humans, wild type mice, STATS knockout mice, TNFR1 and TNFR2 knockout mice, and alpha and beta estrogen receptor knockout mice. ..
  11. mt-Nd2 and Resistance to Autoimmune Diabetes
    Clayton E Mathews; Fiscal Year: 2013
    ..The studies, as proposed, will provide meaningful data on both the early apoptotic signals that result in human beta cell death as well as insights into how ND2a protects human beta cells. ..
  12. MECHANICAL STIMULATION OF IVD CELLS
    Lori A Setton; Fiscal Year: 2013
    ....
  13. CYTOPROTECTIVE EFFECTS OF INFLAMMATION MEDIATED MEMBRANE REPAIR
    DOUGLAS LOWELL MANN; Fiscal Year: 2013
    ..abstract_text> ..
  14. mt-Nd2 and Resistance to Autoimmune Diabetes
    Clayton E Mathews; Fiscal Year: 2011
    ..The studies, as proposed, will provide meaningful data on both the early apoptotic signals that results in beta cell death as well as insights into how ND2a protects beta cells. ..
  15. Molecular Markers in Discoid Lupus Erythematous
    BENJAMIN FRANKLIN CHONG; Fiscal Year: 2013
    ..Moreover, knowledge of genes associated with systemic involvement in DLE subjects will enhance understanding of disease course. ..
  16. Respiratory Muscle Weakness in Chronic Inflammation
    Francisco H Andrade; Fiscal Year: 2013
    ..The goal of this project is to identify new therapies that preserve respiratory muscle function in order to lessen illness and prolong life. ..
  17. New Strategies to Prevent Death from Influenza
    Kendall A Smith; Fiscal Year: 2010
    ..If successful, this research effort will provide the foundation for the development of a universal approach to the prevention and treatment of one of the world's most dangerous microbes, one that kills hundreds of thousands yearly. ..
  18. Role and Mechanism of NLRX1-mediated Cell Stress Response in Insulin Resistance
    Haitao Wen; Fiscal Year: 2013
    ..Further studies could lead to the identification of new therapeutic targets and ultimately help develop rational, mechanism-based treatment strategies that target obesity and diabetes. ..
  19. NGF Receptor Regulates Prostate Growth
    Daniel Djakiew; Fiscal Year: 2009
    ..By lead compound optimization, we anticipate the development of novel chemotherapeutics with a novel mechanism of action for the treatment of prostate cancer. ..
  20. Cytoprotective cytokine signaling and reperfusion injury
    DOUGLAS LOWELL MANN; Fiscal Year: 2010
    ....
  21. TNF-like weak inducer of apoptosis (TWEAK) signaling in lupus nephritis
    Chaim Putterman; Fiscal Year: 2013
    ..Determine the effect of TWEAK signaling in resident kidney cells, and particularly podocytes, in the development of LN, including albuminuria and glomerulosclerosis. ..
  22. Sensitizing Leukemia Stem Cells to NF-kB Inhibition by Blocking TNF Signaling
    Andrew Volk; Fiscal Year: 2013
    ..The expected results of this study will significantly contribute to furthering the understanding of leukemia, an may also point the way toward novel strategies for future therapies. ..
  23. Modeling monocyte and macrophage based gene therapy for neuroAIDS
    Yuanan Lu; Fiscal Year: 2013
    ..Successful completion of this study is expected to provide significant insight into new approaches for combating neuroAIDS and other neurologic disorders. ..
  24. CpnA's role in cAMP signaling and the actin cytoskeleton in Dictyostelium
    Cynthia K Damer; Fiscal Year: 2013
    ..Increasing our scientific knowledge of how copines function could lead to a better understanding of cancer and immune cell-related diseases. ..
  25. Bridging Pediatric and Adult Biomarkers of Graft-Versus-Host-Disease
    Jamie L Renbarger; Fiscal Year: 2013
    ..Ultimately, we propose the discovery of a GVHD-specific drug to increase efficacy and lower toxicity. ..
  26. TRADD as a Regulator of Cytokine Signaling in Glia
    ETTY BENVENISTE; Fiscal Year: 2009
    ..Our studies will provide a comprehensive assessment of TRADD function in cytokine signaling, thereby advancing our understanding of this novel signaling pathway in the context of macrophage/microglial activation and neuroinflammation. ..
  27. TNF Signaling in Neurodegeneration
    MARIALOURDES G TANSEY; Fiscal Year: 2010
    ....
  28. BTK SIGNALING IN B CELL SURVIVAL BY BAFF-R
    Wasif N Khan; Fiscal Year: 2011
    ..The proposed research will illuminate novel mechanisms by which Btk regulates B cell survival critical for normal B cell survival in the healthy immune system as well as B cell autoimmune and immunodeficiency diseases. ..
  29. Extra-translational roles of aminoacyl tRNA synthetases in connection to disease
    Xiang Lei Yang; Fiscal Year: 2013
    ..The knowledge we gain in this study will also shed light on other neurological diseases such as Amyotrophic Lateral Sclerosis (Lou Gehrig's disease) and Parkinson's disease. ..
  30. Anti Herpesvirus Signaling by LTab and LIGHT
    Carl F Ware; Fiscal Year: 2013
    ..We have established a highly interactive group of virologists and autoimmune disease specialists as collaborators to assist in the experimental approach and data analysis. ..
  31. Role of CD40 in Obesity-Induced Adipose Tissue Inflammation &Insulin Resistance
    David L Morris; Fiscal Year: 2013
    ....
  32. The role of MCPIP1 in regulating NF-kB signaling and macrophage activation
    Mingui Fu; Fiscal Year: 2012
    ..abstract_text> ..
  33. Mechanism(s) of CD8 T cell-mediated Chlamydia-induced reproductive pathology
    ASHLESH KRISHNA MURTHY; Fiscal Year: 2013
    ..We will test this hypothesis by: Aim 1. Determine the role of TNF-a receptors in CD8+ T cell mediated chlamydial pathogenesis, and Aim 2. Determine the role of connexin 43 in CD8+ T cell mediated chlamydial pathogenesis ..
  34. Viral Mediated Type I Interferon Induction
    Genhong Cheng; Fiscal Year: 2013
    ..We will also develop novel therapeutic agents to treat disease models associated with DNA virus infections such as genital herpes. ..
  35. The role of Fas-associated death domain in necroptosis in vivo
    Astar Winoto; Fiscal Year: 2013
    ..Successful completion of these aims will greatly enhance our understanding of the host- pathogen interaction and the physiological role of necroptosis. ! ! ! ..
  36. Structure-Function Relationships in the IL-17 Receptor
    Sarah L Gaffen; Fiscal Year: 2012
    ..Moreover, using that information, we aim to design specific blockers of the IL-17 receptor that might ultimately be used therapeutically to treat autoimmune conditions. ..
  37. VEGI-192 As An Anticancer Therapeutic Agent
    LUYUAN LI; Fiscal Year: 2010
    ....
  38. LIGHT_HVEM_BTLA axis in protective anti_viral immunity
    Shahram Salek-Ardakani; Fiscal Year: 2013
    ..Collectively, these studies will provide new insight into the development of anti-viral CD8 T cell responses and facilitate the translational research development of novel adjuvant and vaccine strategies. ..
  39. IAP Family Proteins and Cancer
    Guy S Salvesen; Fiscal Year: 2013
    ....
  40. Fatty acids-mediated inflammation and ethnic disparity in pregnancy outcome
    Xinhua Chen; Fiscal Year: 2013
    ....
  41. ADPKD: Understanding mechanisms, Discovering treatments.
    Xiaogang Li; Fiscal Year: 2013
    ..The information from our studies will be likely to open new avenues in the research of ADPKD and establish the foundation for developing effective therapies of the disease. ..
  42. Role of NF-kB activation in acute allograft rejection
    Maria Luisa Alegre; Fiscal Year: 2009
    ..To determine the mechanism by which CARMA1 regulates the thymic development of nTregs. Specific Aim 2. To delineate the mechanism by which CARMA1-NF-[unreadable]B reciprocally regulates iTreg versus Th17 differentiation. ..
  43. Protection of vaccine immunity by inhibiting Fas/FasL signaling
    Maria S Salvato; Fiscal Year: 2010
    ..Our studies propose to test inhibitors of cell-death signals that would have short-term effects and highly-specific targets, yet would not interfere with the development of strong responses against cancers or infections. ..
  44. Role of NF-kB activation in acute allograft rejection
    Maria Luisa Alegre; Fiscal Year: 2013
    ..In this application we propose to investigate the mechanisms by which TCR-CARMA1-NF-?B regulates formation of nTregs, iTregs and Th17 cells and how these effects impact allograft fate. ..
  45. Progranulin Intervention in Inflammatory Bowel Diseases
    Chuanju Liu; Fiscal Year: 2013
    ....
  46. Pathways of plasma cell differentiation in autoimmunity
    Loren D Erickson; Fiscal Year: 2013
    ....
  47. CYTOKINES AND INFLAMMATORY BOWEL DISEASE
    Fabio Cominelli; Fiscal Year: 2009
    ..abstract_text> ..
  48. RIPK1: A new target for traumatic brain injury?
    Michael J Whalen; Fiscal Year: 2013
    ..The proposed drug therapy might reduce brain cell death as well as improve learning and memory in survivors, and thereby improve their quality of life. ..
  49. Pathogenesis and Therapy of HIV-Related Neuropathic Pain
    Shuanglin Hao; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: proposal will investigate the mechanism of HIV-related neuropathic pain. The study may provide a new approach to treatment of HIV-related pain. ..
  50. Plasma Osteoprotegerin and Adverse Outcomes in CHD Patients
    Iftikhar J Kullo; Fiscal Year: 2013
    ..Incremental predictive utility will be assessed by the c-statistic, net reclassification index, and integrated discriminaton improvement (IDI). ..
  51. Redox Mechanisms of Ischemia Reperfusion Injury in the Liver
    John F Engelhardt; Fiscal Year: 2013
    ..Such studies may lead to therapeutic interventions that make it possible to reduce liver injury following I/R by modulating the redox-dependent responses most deleterious to the liver. ..
  52. Mechanisms of CD8+ T Cell Apoptosis During Acute and Chronic Viral Infections
    JASON MITCHELL GRAYSON; Fiscal Year: 2010
    ..abstract_text> ..
  53. Pro & Anti-Inflammatory Cytokines in Colorectal Cancer
    GLORIA YF HO; Fiscal Year: 2010
    ..These high-risk individuals may benefit from prophylactic NSAIDS for prevention of colorectal cancer. ..
  54. ATHEROSCLEROSIS AND VASCULAR BIOLOGY TRAINING CENTER
    CHRISTIE MITCHELL BALLANTYNE; Fiscal Year: 2012
    ....
  55. TNF receptor-2 signaling in arteriogenesis/angiogenesis
    Wang Min; Fiscal Year: 2010
    ..Growth and maturation of blood vessels are critical for the repair of ischemic heart, brain and extremity. We will study the role of a membrane receptor TNFR2 in the process. Our work may lead to better treatments for ischemic diseases. ..
  56. ANALYSIS OF BIDIRECTIONAL SIGNALING MECHANISMS FOR BTLA AND HVEM IN AUTOIMMUNITY
    Kenneth M Murphy; Fiscal Year: 2010
    ..Importantly, BTLA has recently been reported to be involved in the susceptibility in humans to rheumatoid arthritis. Thus, our proposed studies into this newly identified but poorly understood molecule are particularly timely. ..
  57. Role of the M1 macrophage response in the progression of chronic kidney disease
    Steven D Crowley; Fiscal Year: 2013
    ..Examining these pathways should lead to more effective strategies for preventing progressive CKD. ..
  58. Regulation of Apoptosis in Renal Ischemia
    Babu J Padanilam; Fiscal Year: 2013
    ..The latter outcome could have a dramatic impact on the quality of life and reducing the health care cost associated with acute kidney injury. ..
  59. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..
  60. Hyperthermia-augmented epithelial apoptosis and acute lung injury
    Jeffrey D Hasday; Fiscal Year: 2013
    ..The pharmacologic studies in aim 4 will provide new preclinical data that may lead to future therapies in patients with ALI. ..
  61. CMV-encoded TNF receptor and viral dissemination
    RAVIT BOGER; Fiscal Year: 2010
    ..Understanding the role of UL144 in allowing viral dissemination and immune evasion, may open a new strategy for drug and vaccine development. ..
  62. 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. ..
  63. Selective and dual-acting Hsp90 and TRAP1 inhibitors
    Duncan McRee; Fiscal Year: 2010
    ....
  64. Decoy receptor 3 and liver cirrhosis
    Sunghee Kim; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  65. Conjunctival Mast Cells in Allergic Eye Disease
    NEAL BARNEY; Fiscal Year: 2007
    ..abstract_text> ..
  66. Soluble Decoy Receptor 3 in Bacterial Infection and Sepsis
    Sunghee Kim; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  67. Inflammation and Infection as Risk Factors in Stroke
    Mitchell Elkind; Fiscal Year: 2006
    ..Nationally recognized experts in stroke epidemiology and basic vascular biology will serve as mentors for these studies. ..
  68. MOLECULAR MECHANISMS OF TUMOR NECROSIS FACTOR
    David Spriggs; Fiscal Year: 1991
    ....
  69. Regulation of lymphocyte survival by NF-kB proteins
    Amer Beg; Fiscal Year: 2004
    ..These studies may also provide insights into development of strategies for enhancing lymphopoiesis under therapeutic settings. ..
  70. REGULATION OF CD8 T CELL IMMUNITY BY TNF RECEPTORS
    Marulasiddappa Suresh; Fiscal Year: 2001
    ....
  71. CD40 SIGNAL TRANSDUCTION
    Claudius Vincenz; Fiscal Year: 1999
    ..Specific Aim 3: Determine if CD40bp and TRAF2 modulate other CD40 signaling events including activation of cytoplasmic src-like kinases and PI3 kinase. ..
  72. Herpes simplex virus receptors and signal transduction
    PATRICIA SPEAR; Fiscal Year: 2003
    ..The studies described in this proposal are distinct from those supported by the parent grant but address questions that arise from findings made in the parent project. ..
  73. Cell-Based Assays for Identifying Anti-RANK Signaling Agents
    Xu Feng; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..