tumor necrosis factor alpha

Summary

Summary: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.

Top Publications

  1. ncbi Regulation and function of NF-kappaB transcription factors in the immune system
    Sivakumar Vallabhapurapu
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, Cancer Center, University of California, San Diego, California 93093, USA
    Annu Rev Immunol 27:693-733. 2009
  2. ncbi HMG-1 as a late mediator of endotoxin lethality in mice
    H Wang
    Department of Emergency Medicine and Department of Surgery, North Shore University Hospital New York University School of Medicine, Manhasset, NY 11030, USA
    Science 285:248-51. 1999
  3. ncbi Identification and characterization of a new member of the TNF family that induces apoptosis
    S R Wiley
    Immunex Research and Development Corporation, Seattle, Washington 98101, USA
    Immunity 3:673-82. 1995
  4. ncbi Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation
    Hong Wang
    Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute, 350 Community Drive, Manhasset, New York 11030, USA
    Nature 421:384-8. 2003
  5. ncbi Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo
    H Walczak
    Immunex Corporation, Seattle, Washington 98101, USA
    Nat Med 5:157-63. 1999
  6. 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
  7. pmc An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection
    J L Flynn
    Howard Hughes Medical Institute, Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461
    J Exp Med 178:2249-54. 1993
  8. ncbi Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent
    J Keane
    Pulmonary Center, Department of Medicine, Boston University School of Medicine, MA 02118, USA
    N Engl J Med 345:1098-104. 2001
  9. ncbi Inflammatory bowel disease
    Daniel K Podolsky
    Gastrointestinal Unit and the Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 347:417-29. 2002
  10. 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

Detail Information

Publications336 found, 100 shown here

  1. ncbi Regulation and function of NF-kappaB transcription factors in the immune system
    Sivakumar Vallabhapurapu
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, Cancer Center, University of California, San Diego, California 93093, USA
    Annu Rev Immunol 27:693-733. 2009
    ..This recent progress is covered in this review...
  2. ncbi HMG-1 as a late mediator of endotoxin lethality in mice
    H Wang
    Department of Emergency Medicine and Department of Surgery, North Shore University Hospital New York University School of Medicine, Manhasset, NY 11030, USA
    Science 285:248-51. 1999
    ..Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target...
  3. ncbi Identification and characterization of a new member of the TNF family that induces apoptosis
    S R Wiley
    Immunex Research and Development Corporation, Seattle, Washington 98101, USA
    Immunity 3:673-82. 1995
    ..Both full-length cell surface expressed TRAIL and picomolar concentrations of soluble TRAIL rapidly induce apoptosis in a wide variety of transformed cell lines of diverse origin...
  4. ncbi Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation
    Hong Wang
    Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute, 350 Community Drive, Manhasset, New York 11030, USA
    Nature 421:384-8. 2003
    ..Thus, the nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway...
  5. ncbi Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo
    H Walczak
    Immunex Corporation, Seattle, Washington 98101, USA
    Nat Med 5:157-63. 1999
    ..17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection...
  6. 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...
  7. pmc An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection
    J L Flynn
    Howard Hughes Medical Institute, Department of Microbiology, Albert Einstein College of Medicine, Bronx, New York 10461
    J Exp Med 178:2249-54. 1993
    ..In contrast to control mice, gko mice exhibit heightened tissue necrosis and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN-gamma...
  8. ncbi Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent
    J Keane
    Pulmonary Center, Department of Medicine, Boston University School of Medicine, MA 02118, USA
    N Engl J Med 345:1098-104. 2001
    Infliximab is a humanized antibody against tumor necrosis factor alpha (TNF-alpha) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab...
  9. ncbi Inflammatory bowel disease
    Daniel K Podolsky
    Gastrointestinal Unit and the Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 347:417-29. 2002
  10. 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...
  11. ncbi NF-kappaB at the crossroads of life and death
    Michael Karin
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Nat Immunol 3:221-7. 2002
    ..However, NF-kappaB cannot function alone. A variety of mechanisms exist to modulate its activity and thereby affect the ultimate outcome of a cell's fate...
  12. ncbi A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells
    R A Black
    Immunex Corporation, Seattle, Washington 98101, USA
    Nature 385:729-33. 1997
    ..Our results should facilitate the development of therapeutically useful inhibitors of TNF-alpha release, and they indicate that an important function of adamalysins may be to shed cell-surface proteins...
  13. 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...
  14. ncbi Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family
    R M Pitti
    Department of Molecular Oncology, Genentech, Inc, South San Francisco, California 94080 4990, USA
    J Biol Chem 271:12687-90. 1996
    ..These results suggest that, along with other family members such as Fas/Apo-1 ligand and TNF, Apo-2L may serve as an extracellular signal that triggers programmed cell death...
  15. ncbi NF-kappaB functions as a tumour promoter in inflammation-associated cancer
    Eli Pikarsky
    Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Nature 431:461-6. 2004
    ..Our studies thus indicate that NF-kappaB is essential for promoting inflammation-associated cancer, and is therefore a potential target for cancer prevention in chronic inflammatory diseases...
  16. 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...
  17. ncbi Signalling pathways of the TNF superfamily: a double-edged sword
    Bharat B Aggarwal
    Cytokine Research Section, Department of Bioimmunotherapy, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Box 143, Houston, Texas, USA
    Nat Rev Immunol 3:745-56. 2003
    ..These cytokines either induce cellular proliferation, survival, differentiation or apoptosis. Blockers of TNF have been approved for human use in treating TNF-linked autoimmune diseases in the United States and other countries...
  18. ncbi CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein
    S D Wright
    Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021
    Science 249:1431-3. 1990
    ..Thus, LPS may induce responses by interacting with a soluble binding protein in serum that then binds the cell surface protein CD14...
  19. ncbi TNF-R1 signaling: a beautiful pathway
    Guoqing Chen
    Tularik Inc, Two Corporate Drive, South San Francisco, CA 94080, USA
    Science 296:1634-5. 2002
    ..We provide an overview of current knowledge of TNF signaling and introduce an STKE Connections Map that depicts a canonical view of this process...
  20. ncbi Antigen-specific T cell sensitization is impaired in IL-17-deficient mice, causing suppression of allergic cellular and humoral responses
    Susumu Nakae
    Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo, Japan
    Immunity 17:375-87. 2002
    ..Our findings indicate that IL-17 plays an important role in activating T cells in allergen-specific T cell-mediated immune responses...
  21. 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...
  22. ncbi Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study
    Joachim Spranger
    Department of Endocrinology, Diabetes and Nutrition, Benjamin Franklin Medical Center, Free University Berlin, Berlin, Germany
    Diabetes 52:812-7. 2003
    ..These data strongly support the hypothesis that a subclinical inflammatory reaction has a role in the pathogenesis of type 2 diabetes...
  23. ncbi Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease
    Alain R Simard
    Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, 2705 Laurier Boul, Quebec G1V 4G2, Canada
    Neuron 49:489-502. 2006
    ..Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques...
  24. ncbi TNF-mediated inflammatory disease
    J R Bradley
    NIHR Cambridge Biomedical Research Centre, Addenbrooke s Hospital, Cambridge, UK
    J Pathol 214:149-60. 2008
    ..The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases...
  25. pmc High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes
    U Andersson
    Department of Medicine, Rheumatology Unit, Karolinska Hospital, 17176 Stockholm, Sweden
    J Exp Med 192:565-70. 2000
    ..Together, these results indicate that, like other cytokine mediators of endotoxin lethality (e.g., TNF and IL-1), extracellular HMG-1 is a regulator of monocyte proinflammatory cytokine synthesis...
  26. ncbi An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow
    M B Lutz
    Department of Dermatology, University of Erlangen, Germany
    J Immunol Methods 223:77-92. 1999
    ..This method allows by simple means the generation of high numbers of murine DC with very low B cell or granulocyte contaminations. It will be valuable to study DC biology notably at the molecular level...
  27. ncbi Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function
    K T Uysal
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Nature 389:610-4. 1997
    ..These results indicate that TNF-alpha is an important mediator of insulin resistance in obesity through its effects on several important sites of insulin action...
  28. ncbi NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase
    O N Ozes
    Department of Microbiology and Immunology, Indiana University School of Medicine, The Walther Oncology Center, Indianapolis 46202, USA
    Nature 401:82-5. 1999
    ..Mutation of this amino acid blocks phosphorylation by Akt or TNF and activation of NF-kappaB. These findings indicate that Akt is part of a signalling pathway that is necessary for inducing key immune and inflammatory responses...
  29. ncbi Cellular responses to interferon-gamma
    U Boehm
    Institute for Genetics, University of Cologne, Koln, Germany
    Annu Rev Immunol 15:749-95. 1997
    ..A promising approach to the complexity of the IFN-gamma response is to extend the analysis of the less understood IFN-gamma-regulated genes in terms of molecular programs functional in pathogen resistance...
  30. ncbi In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha
    R T Gazzinelli
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    J Immunol 157:798-805. 1996
    ..Together the data suggest that endogenous IL-10 synthesis plays an important role in vivo in down-regulating monokine and IFN-gamma responses to acute intracellular infection, thereby preventing host immunopathology...
  31. ncbi A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha
    Takayoshi Suganami
    Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101 0062, Japan
    Arterioscler Thromb Vasc Biol 25:2062-8. 2005
    ..Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate...
  32. ncbi beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis
    C K Combs
    Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Neurosci 21:1179-88. 2001
    ..This study demonstrates a functional linkage between beta-amyloid-dependent activation of microglia and several characteristic markers of neuronal death occurring in Alzheimer's disease brains...
  33. ncbi Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options
    C A Gogos
    Department of Medicine, Section of Infectious Diseases, Patras University Medical School, Patras, Greece
    J Infect Dis 181:176-80. 2000
    ....
  34. ncbi TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis
    Y Chicheportiche
    Department of Pathology, University of Geneva, 1211 Geneva 4, Switzerland
    J Biol Chem 272:32401-10. 1997
    ....
  35. pmc Evidence that cytokines play a role in rheumatoid arthritis
    Fionula M Brennan
    Kennedy Institute of Rheumatology, Imperial College London, London, UK
    J Clin Invest 118:3537-45. 2008
    ..In this Review, we discuss the biologic contribution and therapeutic potential of the major cytokine families to RA pathology, focusing on molecules contained within the TNF-alpha, IL-1, IL-6, IL-23, and IL-2 families...
  36. ncbi Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner
    Hideyuki Takeuchi
    Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo cho, Chikusa ku, Japan
    J Biol Chem 281:21362-8. 2006
    ..These drugs may give us a new therapeutic strategy against neurodegenerative diseases with minimum adverse side effects...
  37. ncbi The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation
    Alexander Hoffmann
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Science 298:1241-5. 2002
    ..Bimodal signal-processing characteristics with respect to stimulus duration are revealed by the model and are shown to generate specificity in gene expression...
  38. 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...
  39. 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...
  40. ncbi Duration of nuclear NF-kappaB action regulated by reversible acetylation
    - Chen Lf
    Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco, CA 94141, USA
    Science 293:1653-7. 2001
    ....
  41. 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...
  42. ncbi Expression and regulation of tumor necrosis factor alpha in normal and malignant ovarian epithelium
    Peter W Szlosarek
    Cancer Research UK, Translational Oncology Laboratory, Barts and The London, Queen Mary s School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom
    Mol Cancer Ther 5:382-90. 2006
    ..The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and both its receptors (TNFRI and TNFRII) are expressed in biopsies of this malignancy...
  43. 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...
  44. ncbi TNF-alpha induces two distinct caspase-8 activation pathways
    Lai Wang
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Cell 133:693-703. 2008
    ..These findings revealed that TNF-alpha is able to induce apoptosis via two distinct caspase-8 activation pathways that are differentially regulated by cIAP1/2 and c-FLIP...
  45. ncbi Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha
    David Stellwagen
    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford Medical School, Palo Alto, California 94305, USA
    J Neurosci 25:3219-28. 2005
    ..These results suggest that TNFalpha can regulate neuronal circuit homeostasis in a manner that may exacerbate excitotoxic damage resulting from neuronal insults...
  46. ncbi High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine
    Noboru Taniguchi
    Faculty of Medicine, Kagoshima University, Japan
    Arthritis Rheum 48:971-81. 2003
    ..The purpose of this study was to demonstrate HMGB-1 expression in vivo and to identify the role of HMGB-1 in the pathogenesis of rheumatoid arthritis (RA)...
  47. ncbi A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB
    J A DiDonato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Nature 388:548-54. 1997
    ..A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation...
  48. ncbi Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL
    J G Emery
    Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 273:14363-7. 1998
    ..OPG inhibits TRAIL-induced apoptosis of Jurkat cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These data suggest potential cross-regulatory mechanisms by OPG and TRAIL...
  49. ncbi Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO
    Chee Kwee Ea
    Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Cell 22:245-57. 2006
    ..protein kinase 1 (RIP1) is essential for the activation of nuclear factor kappaB (NF-kappaB) by tumor necrosis factor alpha (TNFalpha)...
  50. ncbi DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL
    Mikhail B Litinskiy
    Division of Molecular Immunology, Department of Pathology and Laboratory Medicine, Joan and Sanford I Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Nat Immunol 3:822-9. 2002
    ..By eliciting CD40-independent Ig class switching and plasmacytoid differentiation, BLyS and APRIL critically link the innate and adaptive immune responses...
  51. pmc T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines
    F Fossiez
    Schering Plough, Laboratory for Immunological Research, Dardilly, France
    J Exp Med 183:2593-603. 1996
    ..These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis...
  52. ncbi Essential role of MD-2 in LPS responsiveness and TLR4 distribution
    Yoshinori Nagai
    Division of Infectious Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Nat Immunol 3:667-72. 2002
    ..Thus, MD-2 is essential for correct intracellular distribution and LPS-recognition of TLR4...
  53. ncbi NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia
    Liya Qin
    Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, NIEHS, NIH, Research Triangle Park, NC 27709, USA
    J Biol Chem 279:1415-21. 2004
    ..Gene expression and release of tumor necrosis factor alpha was much lower in PHOX-/- mice than in control PHOX+/+ mice...
  54. pmc Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration
    Liya Qin
    Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
    Glia 55:453-62. 2007
    ..A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis factor alpha (TNFalpha, 0.25 mg/kg, i.p...
  55. ncbi Essential function for the kinase TAK1 in innate and adaptive immune responses
    Shintaro Sato
    Akira Innate Immunity Project, Exploratory Research for Advanced Technology, Japan Science and Technology Agency
    Nat Immunol 6:1087-95. 2005
    ..However, TAK1-deficient B cells were able to activate NF-kappaB but not the kinase Jnk in response to B cell receptor stimulation. These results collectively indicate that TAK1 is key in the cellular response to a variety of stimuli...
  56. ncbi Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies
    D Kontoyiannis
    Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece
    Immunity 10:387-98. 1999
    ..e., chronic inflammatory arthritis and Crohn's-like inflammatory bowel disease, suggests that defective function of ARE may be etiopathogenic for the development of analogous human pathologies...
  57. ncbi Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study
    Arthur Kavanaugh
    University of California, San Diego, La Jolla, CA 92093 0943, USA
    Arthritis Rheum 60:976-86. 2009
    ..To assess the efficacy and safety of golimumab in patients with active psoriatic arthritis (PsA)...
  58. ncbi Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages
    J Keane
    Pulmonary Center, Boston University School of Medicine, Boston MA 02118, USA
    J Immunol 164:2016-20. 2000
    ....
  59. ncbi Inhibition of JNK activation through NF-kappaB target genes
    G Tang
    Ben May Institute for Cancer Research, Committee on Cancer Biology, University of Chicago, 5841 S. Maryland Avenue, MC 6027, Chicago, Illinois 60637, USA
    Nature 414:313-7. 2001
    ..This negative crosstalk, which is specific to TNF-alpha signalling and does not affect JNK activation by interleukin-1 (IL-1), contributes to inhibition of apoptosis...
  60. ncbi The inflammatory response in myocardial infarction
    Nikolaos G Frangogiannis
    Section of Cardiovascular Sciences, Department of Medicine, Baylor College of Medicine and the DeBakey Heart Center, One Baylor Plaza M S F 602, Houston, TX 77030, USA
    Cardiovasc Res 53:31-47. 2002
    ..Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction...
  61. ncbi A nucleosomal function for IkappaB kinase-alpha in NF-kappaB-dependent gene expression
    Vasiliki Anest
    Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    Nature 423:659-63. 2003
    ..These findings provide additional insight into the role of the IKK complex in NF-kappaB-regulated gene expression...
  62. ncbi Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients
    J Crespo
    Institute of Digestive Diseases, University Hospital Marques de Valdecilla, School of Medicine, Santander, Spain
    Hepatology 34:1158-63. 2001
    The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor alpha (TNF-alpha) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied...
  63. pmc Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression
    Ping Hu
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 702 Light Hall, Nashville, TN 37232 0615, USA
    Mol Cell Biol 26:3071-84. 2006
    ..Gene expression analysis revealed that ER stress-induced expression of tumor necrosis factor alpha (TNF-alpha) was IRE1alpha and NF-kappaB dependent...
  64. 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...
  65. ncbi Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)
    Douglas L Mann
    Winters Center for Heart Failure Research, Baylor College of Medicine and the Houston VA, Houston, Tex 77030, USA
    Circulation 109:1594-602. 2004
    ..Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure...
  66. pmc TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo
    Jae Hyuck Shim
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 19:2668-81. 2005
    ..Therefore, our studies suggests that TAK1 acts as an upstream activating kinase for IKKbeta and JNK, but not IKKalpha, revealing an unexpectedly specific role of TAK1 in inflammatory signaling pathways...
  67. ncbi The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previo
    Ferdinand C Breedveld
    Department of Rheumatology, Leiden University Medical Centre, Albinusdreef 2, C4 R Postbox 9600, Leiden 2300 RC, The Netherlands
    Arthritis Rheum 54:26-37. 2006
    ..To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment...
  68. pmc Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity
    Mauritius Menges
    Department of Dermatology, University of Erlangen, Erlangen 91052, Germany
    J Exp Med 195:15-21. 2002
    ..In conclusion, this study describes that stimulation by TNF-alpha results in incompletely matured DCs (semi-mature DCs) which induce peptide-specific IL-10-producing T cells in vivo and prevent EAE...
  69. 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
    ..Here, we show that a protein produced by glia, tumor necrosis factor alpha (TNFalpha), enhances synaptic efficacy by increasing surface expression of AMPA receptors...
  70. ncbi MAPKAP kinase 2 is essential for LPS-induced TNF-alpha biosynthesis
    A Kotlyarov
    Martin Luther University Halle Wittenberg, Germany
    Nat Cell Biol 1:94-7. 1999
    ..We conclude that MK2 is an essential component in the inflammatory response which regulates biosynthesis of TNF-alpha at a post-transcriptional level...
  71. 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...
  72. ncbi IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain
    H Sakurai
    Discovery Research Laboratory, Tanabe Seiyaku Co, Ltd, 16 89 Kashima 3 chome, Yodogawa ku, Osaka 532 8505, Japan
    J Biol Chem 274:30353-6. 1999
    ..Furthermore, activation of IKKs by NF-kappaB-inducing kinase induced phosphorylation of p65 in vivo. Our finding, together with previous observations, suggests dual roles for IKK complex in the regulation of NF-kappaB.IkappaB complex...
  73. pmc Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines
    T W Chun
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Exp Med 188:83-91. 1998
    ....
  74. 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...
  75. pmc Characterization of tumor necrosis factor-deficient mice
    M W Marino
    Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 94:8093-8. 1997
    ..parvum-induced inflammatory process, indicating a strong gene dose requirement for different actions of TNF...
  76. 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...
  77. pmc Tumor necrosis factor alpha represses bone morphogenetic protein (BMP) signaling by interfering with the DNA binding of Smads through the activation of NF-kappaB
    Masato Yamazaki
    Departments of Biosciences, Center for Oral Biological Research, Kyushu Dental College, Kitakyushu shi, Fukuoka 803 8580
    J Biol Chem 284:35987-95. 2009
    ..b>Tumor necrosis factor alpha (TNFalpha) inhibits both osteoblast differentiation and bone formation induced by BMPs...
  78. pmc Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord
    Yasuhiko Kawasaki
    Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 28:5189-94. 2008
    ..PICs may further induce long-term synaptic plasticity through CREB-mediated gene transcription. Blockade of PIC signaling could be an effective way to suppress central sensitization and alleviate chronic pain...
  79. pmc Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis
    Christopher T Ritchlin
    Allergy, Immunology and Rheumatology Unit, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Clin Invest 111:821-31. 2003
    ..This leads to osteoclastogenesis at the erosion front and in subchondral bone, resulting in a bidirectional assault on psoriatic bone...
  80. ncbi Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes
    D E Moller
    Departments of Molecular Endocrinology and Metabolic Disorders, Merck Research Laboratories, Rahway, NJ 07065, USA
    Trends Endocrinol Metab 11:212-7. 2000
    b>Tumor necrosis factor alpha (TNF-alpha) has well-described effects on lipid metabolism in the context of acute inflammation, as in sepsis...
  81. ncbi TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB
    Harald Ehrhardt
    Dr von Haunersches Kinderspital, Department of Hematology Oncology, Lindwurmstr 4, Munich 80337, Germany
    Oncogene 22:3842-52. 2003
    ..Given the promising therapeutic potential of TRAIL as a novel anticancer drug, TRAIL-mediated survival or proliferation of target cells may restrict its use to apoptosis-sensitive tumors...
  82. pmc Tumor necrosis factor alpha protects against lethal West Nile virus infection by promoting trafficking of mononuclear leukocytes into the central nervous system
    Bimmi Shrestha
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St Louis, MO 63110, USA
    J Virol 82:8956-64. 2008
    ..However, studies using cell culture offer conflicting answers regarding whether tumor necrosis factor alpha (TNF-alpha) has an anti-WNV function...
  83. 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...
  84. ncbi Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks
    Stanley B Cohen
    Radiant Research, Dallas, Texas 75235, USA
    Arthritis Rheum 54:2793-806. 2006
    ....
  85. 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...
  86. pmc Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release
    K Gronert
    Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Exp Med 187:1285-94. 1998
    ..Taken together, these results identify an endogenous pathway for downregulating mucosal inflammatory events and suggest a potential therapeutic benefit for LXA4 stable analogs...
  87. ncbi TNF-alpha is a predictor of insulin resistance in human pregnancy
    John P Kirwan
    Department of Reproductive Biology, Case Western Reserve University School of Medicine at MetroHealth Medical Center, Bell Greve Building Rm G 232E, 2500 MetroHealth Drive, Cleveland, OH 44109 1998, USA
    Diabetes 51:2207-13. 2002
    ....
  88. ncbi Rheumatoid arthritis
    Lars Klareskog
    Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
    Lancet 373:659-72. 2009
    ..Understanding the cause and pathogenesis of different rheumatoid arthritis subsets will lead not only to individualised treatments during early phases of the illness but also, possibly, to disease prevention...
  89. ncbi An essential role for ectodomain shedding in mammalian development
    J J Peschon
    Immunex Corporation, Seattle, WA 98101, USA
    Science 282:1281-4. 1998
    ..The phenotype of mice lacking TACE suggests an essential role for soluble TGFalpha in normal development and emphasizes the importance of protein ectodomain shedding in vivo...
  90. ncbi The molecular architecture of the TNF superfamily
    Jean Luc Bodmer
    Institute of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066, Epalinges, Switzerland
    Trends Biochem Sci 27:19-26. 2002
    ..Protein folds reminiscent of the THD and CRD are also found in other protein families, raising the possibility that the mode of interaction between TNF and TNF receptors might be conserved in other contexts...
  91. pmc Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy
    Jing Cui
    Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Arthritis Rheum 62:1849-61. 2010
    Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA)...
  92. ncbi Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration
    Z M Ding
    Speros P Martel Laboratory of Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
    J Immunol 163:5029-38. 1999
    ..Neutrophil extravasation in response to TNF-alpha in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased...
  93. ncbi Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines
    A N Vgontzas
    Department of Psychiatry, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Clin Endocrinol Metab 89:2119-26. 2004
    ..Given the potential association of these behavioral and physical alterations with health, well-being, and public safety, the idea that sleep or parts of it are optional should be regarded with caution...
  94. ncbi Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock
    Esmerina Tili
    Ohio State University, Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Columbus, OH 43210, USA
    J Immunol 179:5082-9. 2007
    ..Altogether, our data suggest that the LPS/TNF-alpha-dependent regulation of miR-155 and miR-125b may be implicated in the response to endotoxin shock, thus offering new targets for drug design...
  95. pmc Tumor necrosis factor alpha inhibits signaling from the insulin receptor
    G S Hotamisligil
    Dana Farber Cancer Institute, Boston, MA 02115
    Proc Natl Acad Sci U S A 91:4854-8. 1994
    ..These results show that TNF-alpha directly interferes with the signaling of insulin through its receptor and consequently blocks biological actions of insulin...
  96. pmc Tumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition of human colonic organoids
    Richard C Bates
    Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Mol Biol Cell 14:1790-800. 2003
    ..These results establish a novel role for the stroma in influencing EMT in colon carcinoma, and they identify a selective advantage to the stromal presence of infiltrating leukocytes in regulating malignant tumor progression...
  97. ncbi Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin
    E Carballo
    Office of Clinical Research and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Science 281:1001-5. 1998
    ..These findings identify TTP as a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its messenger RNA. This pathway represents a potential target for anti-TNF-alpha therapies...
  98. ncbi IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology
    Steeve Kwan Tat
    Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculte de Medecine, 1 rue Gaston Veil, BP 53508, 44035 Nantes 1, France
    Cytokine Growth Factor Rev 15:49-60. 2004
    ..The interactions between these three groups are presented within the framework of bone resorption pathophysiology such as tumor associated osteolysis. The central role of the OPG/RANK/RANKL triad is pointed out...
  99. ncbi Oscillations in NF-kappaB signaling control the dynamics of gene expression
    D E Nelson
    Centre for Cell Imaging, School of Biological Sciences, Bioscience Research Building, Crown Street, Liverpool, L69 7ZB, UK
    Science 306:704-8. 2004
    ..The functional consequences of NF-kappaB signaling may thus depend on number, period, and amplitude of oscillations...
  100. ncbi Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability
    E Carballo
    Office of Clinical Research and Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Blood 95:1891-9. 2000
    ..TTP appears to be a physiological regulator of GM-CSF mRNA deadenylation and stability. (Blood. 2000;95:1891-1899)..
  101. ncbi Dual role of tumor necrosis factor alpha in brain injury
    E Shohami
    Department of Pharmacology, Hebrew University School of Pharmacy, Jerusalem, Israel
    Cytokine Growth Factor Rev 10:119-30. 1999
    ..It is suggested that the appropriate context of mediators, at any given time after brain injury may well determine whether the effect of TNF alpha is protective or toxic...

Research Grants71

  1. Autonomic, Endothelial, and Inflammatory Correlates of Sleep Duration
    MERCEDES RENEE CARNETHON; Fiscal Year: 2012
    ..Findings from this study will suggest mechanisms to explain the prior observed associations between sleep duration and CVD risk factors. ..
  2. Effects of Evoked Resistance Training and Testosterone after Spinal Cord Injury
    Ashraf Gorgey; Fiscal Year: 2012
    ..free fatty acids, serum total and free testosterone and IGF-1), and cytokines (c-reactive protein, tumor necrosis factor alpha and IL-6 as inflammatory biomarkers) after 16 weeks of training+Tp and detraining...
  3. Mechanisms of hepcidin effects in the anemia of chronic disease
    Robert T Means; Fiscal Year: 2013
    ..The proposed studies can potentially lead to an enhanced understanding of the mechanisms of ACD, and therefore to more effective therapy. ..
  4. Mitochondrial Dysfunction and Adipose Insulin Resistance
    David A Bernlohr; Fiscal Year: 2013
    ..If the hypothesis is proven to be correct, the study would be immediately translatable to human biology and afford a new view of how type 2 diabetes may be combated. ..
  5. Human Beta-Defensin-1 in HSV-1 Innate Immunity
    LISA KATHLEEN RYAN; Fiscal Year: 2010
    ..The long-range goal of our research is to understand the role of -defensins in the innate immune defense against viruses so that novel therapies can be developed from our findings. ..
  6. The Role of Decidual Innate Immunity in the Pathogenesis of Preeclampsia
    Se Te Joseph Huang; Fiscal Year: 2012
    ..This study of the immunological basis of preeclampsia will result in new therapies to combat this complication during pregnancy. Hence, the welfare of affected families and society will be considerably improved. ..
  7. Inhibition of bone formation by Prx1
    Mark S Nanes; Fiscal Year: 2013
    ..Understanding this mechanism will allow us to find new medications that stimulate new bone formation and regeneration of tissue in veterans who suffer from arthritis, aging, and menopause associated fractures. ..
  8. Mitochondrial Dysfunction and Adipose Insulin Resistance
    DAVID BERNLOHR; Fiscal Year: 2009
    ..Aim 3. Develop and characterize aP2-HA-GSTA4 transgenic mice maintained on low and high fat diets. Aim 4. Characterize the regulation of insulin signaling by the Trx2-ASK1-JNK pathway in animal and cell culture models...
  9. Alcohol, Proteasome Dysfunction in Liver Injury
    Craig J McClain; Fiscal Year: 2013
    ....
  10. Radiation-Induced Osteoporosis in Women with Cancer: Mechanisms and Prevention
    Ted A Bateman; Fiscal Year: 2013
    ....
  11. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ....
  12. Molecular Mechanism of Immune Therapy for Bone Marrow Failures
    Pearlie K Epling-Burnette; Fiscal Year: 2013
    ..Additionally, the efficacy of pharmacological inhibitors to block homing to the bone marrow will be tested to provide critical pre-clinical data for application to clinical studies in patients in the future. ..
  13. Extracellular ubiquitin: role in myocyte apoptosis and myocardial remodeling
    Krishna Singh; Fiscal Year: 2010
    ....
  14. Treatment of Inflammatory Bowel Disease with Ceramidase Inhibitors
    Lynn W Maines; Fiscal Year: 2012
    ..Extensive work, including our Preliminary Studies, suggests that inhibition of neutral ceramidase may provide a new therapy for these diseases. The proposed studies will provide the first test of this hypothesis. ..
  15. Phenotyping Major Depression with Increased Inflammation
    Andrew H Miller; Fiscal Year: 2013
    ..abstract_text> ..
  16. Effects of GSH +/- Arginine on Markers of Inflammation Among Adults with CVD Risk
    Christopher D Gardner; Fiscal Year: 2010
    ....
  17. Nutrition and Anabolic Interventions in Cancer Cachexia
    Melinda Sheffield-Moore; Fiscal Year: 2013
    ..Results from this study may lead to better ways of preventing cancer-related weight loss, and improve the quality of life and survival of those affected by cervical cancer. ..
  18. Mindfulness Based Stress Reduction as an Adjunctive Treatment for Psoriasis
    Jan A Moynihan; Fiscal Year: 2013
    ....
  19. Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Joint Pain
    Karen H Costenbader; Fiscal Year: 2013
    ....
  20. Pathogenesis of Postoperative Cognitive Dysfunction
    Zhongcong Xie; Fiscal Year: 2013
    ..This proposal aims to investigate an understudied topic in an innovative system by testing novel hypotheses. Our efforts would ultimately lead to safer surgical care and better post-operative outcomes for senior patients. ..
  21. A Prospective Study of Adiposity and Subclinical Coronary Artery Disease
    CHRISTINA LYNN WASSEL; Fiscal Year: 2010
    ....
  22. Calorie Restriction &Body Composition, Function, &QoL in Older Adults
    Julie L Locher; Fiscal Year: 2013
    ....
  23. Control of Drug Delivery to the CNS: Modulating P-glycoprotein Activity
    William A Banks; Fiscal Year: 2013
    ..P-gp at the brain endothelial cell is inhibited by lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF)...
  24. Nebraska/Kansas Blood and Marrow Transplant Research Network
    JULIE MARIE VOSE; Fiscal Year: 2013
    ..endothelial growth factor (VEGF), soluble Interleukin-2 receptor (slL2r), lnterleukein-12 (ILI 2), and tumor necrosis factor alpha (TNFa) in the post transplant period and correlate the results with the event-free survival (EFS) and ..
  25. Hepatocyte Nox proteins in the pathogenesis of hepatocellular carcinoma
    Jinah Choi; Fiscal Year: 2013
    ..Toll-like receptor 4 (TLR4) and tumor necrosis factor alpha (TNF?) are elevated in hepatitis C patients...
  26. The biology of blood-testis barrier dynamics
    C Yan Cheng; Fiscal Year: 2013
    ..It also offers new insight into: (i) developing novel approaches for male contraception, and (ii) the causes of unexplained male infertility. ..
  27. Cyclic AMP, Cytokine Modulation and Alcoholic Liver Disease
    Craig J McClain; Fiscal Year: 2013
    ..The major problem to be investigated in this proposal is the mechanism(s) for this dysregulated cytokine metabolism, and our overall goal is the development of novel therapeutic interventions. ..
  28. Caveolins in the Pathogenesis of Idiopathic Pulmonary Fibrosis
    Dan N Predescu; Fiscal Year: 2010
    ..End of Abstract) ..
  29. 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. ..
  30. MECHANISMS OF RETINAL VASCULAR PERMEABILITY IN DIABETES
    DAVID ANTONETTI; Fiscal Year: 2013
    ..Further, the proposal will explore the link between vascular permeability and angiogenesis and the role of the tight junction protein occludin in endothelial cell growth control. ..
  31. Predicting persistent Organ Failure early in Acute Pancreatitis
    Georgios I Papachristou; Fiscal Year: 2013
    ..e. tumor necrosis factor-a inhibitors. ..
  32. Tea Polyphenols in Chemoprevention of Prostate Cancer
    SUSANNE MARGARETE HENNING; Fiscal Year: 2011
    ..we will determine the effect of the six metabolites on apoptosis, Bax/Bcl-2 and NFkB- DNA binding after tumor necrosis factor alpha stimulation in LNCaP cells...
  33. Non-Hodgkin lymphoma in women: reproductive, hormonal and genetic factors
    Paige M Bracci; Fiscal Year: 2011
    ..COMT), and in immune/inflammatory pathways include interleukins (IL), nuclear factor kappa B (NF-:B), tumor necrosis factor alpha (TNF-1) and lymphotoxin alpha (LTA)...
  34. Genes and Hormonal Fetal Antecedents to Sex Differencs in the Brain in Depression
    Jill M Goldstein; Fiscal Year: 2011
    ..An understanding of the fetal mechanisms associated with sex differences in MOD will have etiologic imolications and imoortance for the development of sex-specific treatments and prevention of MOD. ..
  35. 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. ..
  36. Inflammation and Sub-Clinical Renal Damage in Cocaine-Dependent African Americans
    ELIZABETH GROOMS NESMITH; Fiscal Year: 2010
    ....
  37. Vascular Mechanisms in Pregnancy-Induced Hypertension
    Raouf A Khalil; Fiscal Year: 2013
    ....
  38. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
    ..This proposal will provide mechanistic insight into how TAX1BP1, Itch and A20 function together to inactivate key signaling molecules and restrict inflammatory signaling pathways. ..
  39. Pathogenic Mechanisms of Pancreatitis
    Rodger A Liddle; Fiscal Year: 2013
    ..These results should help both elucidate the importance of primary sensory innervation in the pathogenesis of pancreatitis and provide possible new strategies for the treatment of pancreatitis. ..
  40. ACTIVATED MACROPHAGES AND OZONE TOXICITY
    DEBRA LYNN LASKIN; Fiscal Year: 2012
    ....
  41. Abnormal Bone Marrow Cells and Diabetic Neuropathy
    Lawrence Chan; Fiscal Year: 2013
    ..The proposed research on the role and mechanism of high glucose-induced PI-BMDCs and PI-BMDC-neuron cell fusion may lead to a fundamental change in our understanding of the pathogenesis of diabetic neuropathy. ..
  42. Dichotomous Roles of Thrombin in Acetaminophen Hepatotoxicity
    ROBERT ANDREW ROTH; Fiscal Year: 2013
    ..Elucidating mechanisms by which APAP-induced liver injury progresses is essential for defining novel strategies to prevent liver failure in patients and for the general understanding of the pathogenesis of drug-induced liver injury. ..
  43. Establishing the Precursors of Osteoporosis in Children
    Xiping Xu; Fiscal Year: 2010
    ....
  44. Pathogenic Mechanisms of Shiga Toxins
    Vernon L Tesh; Fiscal Year: 2010
    ..An improved understanding of how these toxins cause disease is necessary to formulate effective therapeutic agents to block disease progression. ..
  45. TNF Alpha in PKC Epsilon Signaling to Carcinogenesis
    Ajit K Verma; Fiscal Year: 2013
    ..development of squamous cell carcinoma (SCC) via increased expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF1) and granulocyte colony-stimulating factor (G-CSF) which may directly promote the proliferation ..
  46. Role of Monocyte Chemoattractant Protein (MCP)-1 in Liver Regeneration
    KRISTEN ANDREA MITCHELL; Fiscal Year: 2010
    ..Finally, this project provides an opportunity for undergraduates at Boise State University to participate in biomedical research and gain an appreciation of the complex regulatory mechanisms that govern regeneration. ..
  47. In vivo imaging of encapsulated stem cells in mouse models of tumor resection
    Khalid A Shah; Fiscal Year: 2013
    ..This will have a major impact in saving the lives of many brain cancer patients. ..
  48. Checkpoints of TNF Gene Regulation
    Anne Goldfeld; Fiscal Year: 2013
    ....
  49. Pregnancy, Pre-eclampsia, Anti-oxidants and Endothelial Cell Function
    Gautam Chaudhuri; Fiscal Year: 2010
    ..Results from our studies will indicate to us which anti-oxidants are likely to be more effective than others and which can be used clinically to prevent this condition. ..
  50. Opioidergic System: Its Role(s) in Glaucoma
    Shahid Husain; Fiscal Year: 2013
    ..Outcomes of this project will provide valuable leads in the discovery of more effective therapies that can delay or prevent vision loss associated with neurodegenerative diseases such as glaucoma. 5 ..
  51. Effect of constitutive Type 2 NF-kB on adipogenesis
    LOTUS KYI LOO; Fiscal Year: 2010
    ....
  52. GROWTH CONTROL OF NORMAL AND CIRRHOTIC HEPATOCYTES
    Kevin E Behrns; Fiscal Year: 2010
    ..exhibited markedly decreased apoptosis after treatment with transforming growth factor beta (TGFbeta), tumor necrosis factor alpha (TNFalpha), and ultraviolet radiation...
  53. DIETARY PATTERNS AND RISK OF CARDIOVASCULAR DISEASE
    Frank B Hu; Fiscal Year: 2013
    ....
  54. Molecular Mechanisms of Genistein in the Prevention of Inflammatory Cytokine (TNF
    Zhenquan Jia; Fiscal Year: 2010
    ..The elucidation of the molecular mechanism(s) of action of genistein will provide clinically related strategies in protecting against atherosclerotic vascular disease. ..
  55. Purinergic signaling in sleep apnea
    Elzbieta Kaczmarek; Fiscal Year: 2012
    ..purinergic receptors, decrease high glucose- induced ROS formation, attenuate inflammatory effects of tumor necrosis factor alpha, and rescue eNOS activity in human endothelial cells cultured in high glucose concentrations...
  56. Histone deacetylase 7 and its interacting proteins in endothelial cells
    Hung Ying Kao; Fiscal Year: 2013
    ..Endothelial cells reprogram their transcriptional network in response to cytokine stimulation such as tumor necrosis factor alpha (TNF1), interleukin (IL), lipopolysaccharide (LPS), or interferons (IFNs)...
  57. 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. ..
  58. Effects of Metabolic Disorders on Bone Marrow-Derived Cell Function
    Gina C Schatteman; Fiscal Year: 2012
    ..e., diabetic mice with metabolic syndrome) we identified four molecules, tumor necrosis factor alpha (TNF1), interleukin 12 (IL-12), monocyte chemoattractant factor 1 (MCP-1), and vascular endothelial ..
  59. Sepsis Outcomes and Aging: Role of Sleep Disruption and the Blood Brain Barrier
    Mark R Opp; Fiscal Year: 2013
    ....
  60. Regulation of IL-6 mediated inflammation and tissue destruction by EGCG
    Salah Uddin Ahmed; Fiscal Year: 2013
    ..Successful completion of this study will lay the foundation for testing EGCG as a treatment option for RA and other inflammatory diseases. ..
  61. Proinflammatory Biomarkers and Post-Breast CancerLymphedema
    Mei Rosemary Fu; Fiscal Year: 2012
    ..Findings of the project are fundamental in developing and testing more intense and personalized interventions to prevent and treat LE among the breast cancer survivors. ..
  62. 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. ..
  63. Lead, Cadmium,Arsenic, and cardiovascular risk in children
    Eliseo Guallar; Fiscal Year: 2011
    ..C-reactive protein [CRP], interleukin-6 [IL-6], intercellular adhesion molecule-1 [ICAM-1], and tumor necrosis factor alpha [TNF-alpha]) in children;and 3) Exposures, cadmium, or arsenic are inversely associated with heart rate ..
  64. Blood Brain Barrier Physiology and HIV Dementia
    HOWARD GENDELMAN; Fiscal Year: 2007
    ..neurotoxins (for example, stromal cell derived factor-one- nitric oxide, platelet activating factor, tumor necrosis factor alpha, among others) that influence monocyte migration into the brain; and 3) by utilizing a blood brain ..
  65. Innate immune suppression following experimental injury
    KRISTIN C GREATHOUSE; Fiscal Year: 2012
    ..leukocytes from whole blood, when stimulated by LPS ex vivo, to produce the pro-inflammatory cytokine tumor necrosis factor alpha (TNF?) in critically injured children who develop NI...
  66. Cytoprotective cytokine signaling and reperfusion injury
    DOUGLAS LOWELL MANN; Fiscal Year: 2010
    ....
  67. FUNCTIONS OF ENDOTHELIAL CELL FACTOR IX BINDING PROTEIN
    David Stern; Fiscal Year: 1992
    ....
  68. 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. ..
  69. MECHANISM FOR TNF-INDUCED MYOCARDIAL DYSFUNCTION
    MARC VISNER; Fiscal Year: 1991
    ..e., mechanical work) and metabolism (MVO2, protein synthesis)...
  70. OVARIAN TUMOR NECROSIS FACTOR
    Paul Terranova; Fiscal Year: 2004
    The objective of this application is to delineate the mechanisms by which tumor necrosis factor alpha (TNF) and in receptor system inhibit gonadotropin-stimulated ovarian granulosa cell estradiol secretion using a mouse model...
  71. EXERCISE AS A MEANS OF ENHANCING IMMUNITY IN THE AGED
    Jeffrey Woods; Fiscal Year: 2001
    ....