hmgb1 protein

Summary

Summary: A 24-kDa HMGB protein that binds to and distorts the minor grove of DNA.

Top Publications

  1. ncbi Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
    Paola Scaffidi
    DIBIT, Istituto Scientifico San Raffaele, 20132 Milano, Italy
    Nature 418:191-5. 2002
  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 DAMPs, PAMPs and alarmins: all we need to know about danger
    Marco E Bianchi
    San Raffaele University, Chromatin Dynamics Unit, Via Olgettina 58, 20132 Milan, Italy
    J Leukoc Biol 81:1-5. 2007
  4. ncbi High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
    Michael T Lotze
    University of Pittsburgh School of Medicine, Room 411, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    Nat Rev Immunol 5:331-42. 2005
  5. ncbi HMGB1 and RAGE in inflammation and cancer
    Gary P Sims
    Department of Respiratory, Inflammation and Autoimmune Disease, MedImmune, Gaithersburg, Maryland 20878, USA
    Annu Rev Immunol 28:367-88. 2010
  6. ncbi Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
    Jane Tian
    Inflammation and Autoimmune Group, Research Department, MedImmune, Gaithersburg, Maryland 20878, USA
    Nat Immunol 8:487-96. 2007
  7. pmc High-mobility group box 1 and cancer
    Daolin Tang
    The DAMP Laboratory, Department of Surgery, G 27 Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Ave, Pittsburgh, PA 15213, USA
    Biochim Biophys Acta 1799:131-40. 2010
  8. ncbi Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein
    Jong Sung Park
    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Biol Chem 279:7370-7. 2004
  9. ncbi Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1)
    Judy R van Beijnum
    Angiogenesis Laboratory, Department of Pathology, Research Institute for Growth and Development GROW, Maastricht University, P O Box 5800, 6202 AZ, Maastricht, The Netherlands
    Angiogenesis 11:91-9. 2008
  10. pmc Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
    Tiziana Bonaldi
    DIBIT, San Raffaele Scientific Institute, San Raffaele University, Via Olgettina 58, 20132 Milan, Italy
    EMBO J 22:5551-60. 2003

Research Grants

  1. Regulation of LPS-mediated HMGB1 Release by Poly (ADP-ribose) Polymerase-1
    RAJESH K ANEJA; Fiscal Year: 2013
  2. CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGS
    Stephen J Lippard; Fiscal Year: 2013
  3. MOLECULAR BIOLOGY OF HEMORRHAGIC SHOCK
    Timothy R Billiar; Fiscal Year: 2013
  4. The Role of Sex in Self Antigen Generation in SLE
    David Stephen Pisetsky; Fiscal Year: 2010
  5. HMG in Post Operative and Traumatic Stress
    Kevin J Tracey; Fiscal Year: 2013
  6. DAMP-RAGE Signaling and Fetal Injury in Inflammation-Induced Preterm Birth
    Irina A Buhimschi; Fiscal Year: 2013
  7. Regulation of HMGB1 Release in Endotoxemia
    Haichao Wang; Fiscal Year: 2013
  8. MECHANISMS OF AUTOIMMUNITY IN SLE
    David Stephen Pisetsky; Fiscal Year: 2013
  9. Endogenous regulators of inflammation in liver ischemia/reperfusion
    Allan Tsung; Fiscal Year: 2013
  10. The role of cell death in Lupus Nephritis
    Roberto Caricchio; Fiscal Year: 2013

Detail Information

Publications378 found, 100 shown here

  1. ncbi Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
    Paola Scaffidi
    DIBIT, Istituto Scientifico San Raffaele, 20132 Milano, Italy
    Nature 418:191-5. 2002
    ..Thus, cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma...
  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 DAMPs, PAMPs and alarmins: all we need to know about danger
    Marco E Bianchi
    San Raffaele University, Chromatin Dynamics Unit, Via Olgettina 58, 20132 Milan, Italy
    J Leukoc Biol 81:1-5. 2007
    ..Endogenous alarmins and exogenous PAMPs therefore convey a similar message and elicit similar responses; they can be considered subgroups of a larger set, the damage-associated molecular patterns (DAMPs)...
  4. ncbi High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
    Michael T Lotze
    University of Pittsburgh School of Medicine, Room 411, 300 Technology Drive, Pittsburgh, Pennsylvania 15219, USA
    Nat Rev Immunol 5:331-42. 2005
    ..Here, we discuss these features of HMGB1 and summarize recent advances that have led to the preclinical development of therapeutics that modulate HMGB1 release and activity...
  5. ncbi HMGB1 and RAGE in inflammation and cancer
    Gary P Sims
    Department of Respiratory, Inflammation and Autoimmune Disease, MedImmune, Gaithersburg, Maryland 20878, USA
    Annu Rev Immunol 28:367-88. 2010
    ..While HMGB1 through interactions with TLRs may also be important, this review focuses on the role of the HMGB1-RAGE axis in inflammation and cancer...
  6. ncbi Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE
    Jane Tian
    Inflammation and Autoimmune Group, Research Department, MedImmune, Gaithersburg, Maryland 20878, USA
    Nat Immunol 8:487-96. 2007
    ..Our data demonstrate a mechanism by which HMGB1 and RAGE activate plasmacytoid dendritic cells and B cells in response to DNA and contribute to autoimmune pathogenesis...
  7. pmc High-mobility group box 1 and cancer
    Daolin Tang
    The DAMP Laboratory, Department of Surgery, G 27 Hillman Cancer Center, University of Pittsburgh Cancer Institute, 5117 Centre Ave, Pittsburgh, PA 15213, USA
    Biochim Biophys Acta 1799:131-40. 2010
    ..Here, we focus on the role of HMGB1 in cancer, the mechanisms by which it contributes to carcinogenesis, and therapeutic strategies based on targeting HMGB1...
  8. ncbi Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein
    Jong Sung Park
    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    J Biol Chem 279:7370-7. 2004
    ..Interactions of HMGB1 with TLR 2 and TLR 4 may provide an explanation for the ability of HMGB1 to generate inflammatory responses that are similar to those initiated by LPS...
  9. ncbi Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1)
    Judy R van Beijnum
    Angiogenesis Laboratory, Department of Pathology, Research Institute for Growth and Development GROW, Maastricht University, P O Box 5800, 6202 AZ, Maastricht, The Netherlands
    Angiogenesis 11:91-9. 2008
    ..In this review, we discuss signaling cascades that HMGB1 can induce via TLRs and RAGE, as well as its contribution to pathologies involving endothelial cells...
  10. pmc Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
    Tiziana Bonaldi
    DIBIT, San Raffaele Scientific Institute, San Raffaele University, Via Olgettina 58, 20132 Milan, Italy
    EMBO J 22:5551-60. 2003
    ..Cytosolic HMGB1 is then concentrated by default into secretory lysosomes, and secreted when monocytic cells receive an appropriate second signal...
  11. ncbi The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system
    O Hori
    Department of Physiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 270:25752-61. 1995
    ....
  12. pmc HMGB1: endogenous danger signaling
    John R Klune
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Mol Med 14:476-84. 2008
    ..The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions...
  13. pmc The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 201:1135-43. 2005
    ..Together, these results demonstrate that HMGB1 is an early mediator of injury and inflammation in liver I/R and implicates TLR4 as one of the receptors that is involved in the process...
  14. 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...
  15. ncbi Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells
    Carmen Fiuza
    Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
    Blood 101:2652-60. 2003
    ..002). Thus, rhHMGB1 elicits proinflammatory responses on endothelial cells and may contribute to alterations in endothelial cell function in human inflammation...
  16. ncbi HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses
    Hideyuki Yanai
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 462:99-103. 2009
    ..These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders...
  17. pmc TLR4 activation mediates kidney ischemia/reperfusion injury
    Huiling Wu
    Collaborative Transplant Research Group, Royal Prince Alfred Hospital and Bosch Institute, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia
    J Clin Invest 117:2847-59. 2007
    ....
  18. pmc CD24 and Siglec-10 selectively repress tissue damage-induced immune responses
    Guo Yun Chen
    Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
    Science 323:1722-5. 2009
    ..Our results reveal that the CD24-Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns...
  19. pmc A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release
    Huan Yang
    Laboratory of Biomedical Science and Department of Medicinal Chemistry, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA
    Proc Natl Acad Sci U S A 107:11942-7. 2010
    ..These results have implications for rationale, design, and development of experimental therapeutics for use in sterile and infectious inflammation...
  20. pmc Redox modification of cysteine residues regulates the cytokine activity of high mobility group box-1 (HMGB1)
    Huan Yang
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America
    Mol Med 18:250-9. 2012
    ..These results reveal critical posttranslational redox mechanisms that control the proinflammatory activity of HMGB1 and its inactivation during pathogenesis...
  21. ncbi HMGB1 is a therapeutic target for sterile inflammation and infection
    Ulf Andersson
    Department of Women s and Children s Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
    Annu Rev Immunol 29:139-62. 2011
    ..Experimental strategies that selectively target HMGB1 and TLR4 effectively reverse and prevent activation of innate immunity and significantly attenuate damage in diverse models of sterile and infection-induced threat...
  22. pmc Reversing established sepsis with antagonists of endogenous high-mobility group box 1
    Huan Yang
    Laboratory of Biomedical Science, North Shore Long Island Jewish Research Institute, 350 Community Drive, Manhasset, NY 11030, USA
    Proc Natl Acad Sci U S A 101:296-301. 2004
    ..These observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating that HMGB1 inhibitors can be administered in a clinically relevant time frame...
  23. pmc A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA
    Stanimir Ivanov
    Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
    Blood 110:1970-81. 2007
    ..However, lack of intracellular TLR9-associated HMGB1 can be compensated by extracellular HMGB1. Thus, the DNA-binding protein HMGB1 shuttles in and out of immune cells and regulates inflammatory responses to CpG-DNA...
  24. 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)...
  25. pmc HMGB1 is an endogenous immune adjuvant released by necrotic cells
    Patrizia Rovere-Querini
    Cancer Immunotherapy and Gene Therapy Program, Clinical Immunology Unit H San Raffaele Scientific Institute and Vita Salute San Raffaele University, DIBIT 3A1, Chromatin Dynamics Unit, Via Olgettina 58, 20132 Milano, Italy
    EMBO Rep 5:825-30. 2004
    ..In vivo, HMGB1 enhances the primary antibody responses to soluble antigens and transforms poorly immunogenic apoptotic lymphoma cells into efficient vaccines...
  26. pmc Blockade of high mobility group box-1 protein attenuates experimental severe acute pancreatitis
    Hidehiro Sawa
    Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Kobe 650 0017, Japan
    World J Gastroenterol 12:7666-70. 2006
    ..To examine the effects of anti-high mobility group box 1 (HMGB1) neutralizing antibody in experimental severe acute pancreatitis (SAP)...
  27. ncbi HMGB1 signals through toll-like receptor (TLR) 4 and TLR2
    Man Yu
    Laboratories of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA
    Shock 26:174-9. 2006
    ..Taken together, our data suggest that there is a differential usage of TLR2 and TLR4 in HMGB1 signaling in primary cells and in established cell lines, adding complexity to studies of HMGB1 signaling which was not previously expected...
  28. ncbi High mobility group box 1 protein interacts with multiple Toll-like receptors
    Jong Sung Park
    Division of Pulmonary Sciences and Critical Care Medicine, Box C272, University of Colorado Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262, USA
    Am J Physiol Cell Physiol 290:C917-24. 2006
    ....
  29. pmc The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway
    Stefania Gardella
    National Cancer Research Institute, Genoa, Italy
    EMBO Rep 3:995-1001. 2002
    ..Thus, in monocytes, non-classical secretion can occur through vescicle compartments that are at least partially distinct...
  30. pmc High-mobility group box 1, oxidative stress, and disease
    Daolin Tang
    The DAMP Laboratory, Department of Surgery, G 27 Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
    Antioxid Redox Signal 14:1315-35. 2011
    ....
  31. pmc HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling
    Allan Tsung
    Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA
    J Exp Med 204:2913-23. 2007
    ..Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling...
  32. ncbi Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities
    Luca Mollica
    Biomolecular NMR Laboratory, Dulbecco Telethon Institute, San Raffaele Scientific Institute, Via Olgettina 58, 20133 Milan, Italy
    Chem Biol 14:431-41. 2007
    ..Our results explain in part the anti-inflammatory properties of glycyrrhizin, and might direct the design of new derivatives with improved HMGB1-binding properties...
  33. pmc HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4
    Milena Schiraldi
    Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland
    J Exp Med 209:551-63. 2012
    ..Thus, inflammatory cell recruitment and activation both depend on HMGB1 via different mechanisms...
  34. ncbi High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity
    Marco E Bianchi
    Faculty of Medicine, San Raffaele University, Milano, Italy
    Immunol Rev 220:35-46. 2007
    ..These immune responses will also be directed against self-antigens that DCs process at the time of injury and can lead to autoimmunity...
  35. ncbi The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation
    Hulda Sigridur Hreggvidsdottir
    Department of Medicine, Rheumatology Research Unit, Karolinska Hospital, Karolinska Institutet, S 171 76 Stockholm, Sweden
    J Leukoc Biol 86:655-62. 2009
    ..HMGB1 thus acts broadly with many but not all immunostimulatory molecules to amplify their activity in a synergistic manner...
  36. ncbi Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures
    Mattia Maroso
    Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy
    Nat Med 16:413-9. 2010
    ..Thus, HMGB1-TLR4 signaling may contribute to generating and perpetuating seizures in humans and might be targeted to attain anticonvulsant effects in epilepsies that are currently resistant to drugs...
  37. pmc High-mobility group box-1 and biomarkers of inflammation in the vitreous from patients with proliferative diabetic retinopathy
    Ahmed M Abu El-Asrar
    Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
    Mol Vis 17:1829-38. 2011
    ..In addition, we examined the expression of HMGB1 in the retinas of diabetic mice...
  38. pmc HMGB1 release and redox regulates autophagy and apoptosis in cancer cells
    D Tang
    The DAMP Laboratory, Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
    Oncogene 29:5299-310. 2010
    ..HMGB1 release, as well as its redox state, thus links autophagy and apoptosis, representing a suitable target when coupled with conventional tumor treatments...
  39. ncbi High-mobility group box-1 in ischemia-reperfusion injury of the heart
    Martin Andrassy
    Department of Medicine III, University of Heidelberg, Heidelberg, Germany
    Circulation 117:3216-26. 2008
    ..Although HMGB1 has been implicated in ischemia/reperfusion (I/R) injury of the liver and lung, its role in I/R injury of the heart remains unclear...
  40. ncbi HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain
    Jung Bin Kim
    Department of Anatomy and Center for Advanced Medical Education BK21 project, Inha University School of Medicine, Jung Gu, Inchon 400 712, Republic of Korea
    J Neurosci 26:6413-21. 2006
    ..Together, these results indicate that HMGB1 functions as a novel proinflammatory cytokine-like factor that connects excitotoxicity-induced acute damage processes and delayed inflammatory processes in the postischemic brain...
  41. ncbi Novel strategies for the treatment of sepsis
    Niels C Riedemann
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Nat Med 9:517-24. 2003
    ..quot; That is now set to change, as research provides hope for new approaches that will be therapeutically effective in humans with sepsis...
  42. ncbi The HMGB1 receptor RAGE mediates ischemic brain damage
    Sajjad Muhammad
    Pharmacological Institute, University of Heidelberg, 69120 Heidelberg, Germany
    J Neurosci 28:12023-31. 2008
    ..RAGE deficiency in bone marrow-derived cells significantly reduced the infarct size. Thus, HMGB1-RAGE signaling links necrosis with macrophage activation and may provide a target for anti-inflammatory therapy in stroke...
  43. ncbi The cytokine activity of HMGB1
    Huan Yang
    Laboratory of Biomedical Science, Institute for Medical Research at North Shore Long Island Jewish System, Manhasset, NY 11030, USA
    J Leukoc Biol 78:1-8. 2005
    ..Finally, the therapeutic potential of blocking HMGB1 in the treatment of inflammatory diseases is discussed...
  44. ncbi The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity
    Michael T Lotze
    Department of Surgery, G 27A Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
    Immunol Rev 220:60-81. 2007
    ....
  45. pmc Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands
    Dachun Yao
    Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
    Diabetes 59:249-55. 2010
    ..Since hyperglycemia-induced reactive oxygen species (ROS) activate many pathways of diabetic tissue damage, the effect of these ROS on RAGE and RAGE ligand expression was evaluated...
  46. ncbi Immunogenic death of colon cancer cells treated with oxaliplatin
    A Tesniere
    INSERM, U848, Villejuif, France
    Oncogene 29:482-91. 2010
    ..In conclusion, OXP induces immunogenic death of CRC cells, and this effect determines its therapeutic efficacy in CRC patients...
  47. ncbi Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-kappaB require the cytoplasmic domain of the receptor but different downstream signaling pathways
    H J Huttunen
    Laboratory of Molecular Neurobiology, Institute of Biotechnology, and Department of Biosciences, Division of Biochemistry, University of Helsinki, Finland
    J Biol Chem 274:19919-24. 1999
    ..These data suggest that distinct signaling pathways are used by RAGE to induce neurite outgrowth and regulate gene expression through NF-kappaB...
  48. pmc High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity
    John Evankovich
    Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 285:39888-97. 2010
    ..Together, these findings suggest that decreased nuclear HDAC1 and HDAC4 activities in hepatocytes following liver I/R is a mechanism that promotes the hyperacetylation and subsequent release of HMGB1...
  49. pmc Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASC
    Stephen B Willingham
    Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell Host Microbe 2:147-59. 2007
    ..While similar proteins mediate pathogen-induced cell death in plants, this report identifies cryopyrin as an important host regulator of programmed pathogen-induced necrosis in animals, a process we term pyronecrosis...
  50. ncbi Masquerader: high mobility group box-1 and cancer
    Jessica E Ellerman
    Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Clin Cancer Res 13:2836-48. 2007
    ..This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy...
  51. pmc The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival
    R Kang
    Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA
    Cell Death Differ 17:666-76. 2010
    ..Our data suggest that targeted inhibition of RAGE or its ligands may serve as novel targets to enhance current cancer therapies...
  52. ncbi Hyperlipidemia stimulates the extracellular release of the nuclear high mobility group box 1 protein
    Raluca Haraba
    Institute of Cellular Biology and Pathology N Simionescu, Bucharest, Romania
    Cell Tissue Res 346:361-8. 2011
    ..The cell culture experiments demonstrated the relocation of HMGB1 protein from the nucleus to cytoplasm under hyperlipidemic stress...
  53. ncbi HMGB1 inhibits cell death in yeast and mammalian cells and is abundantly expressed in human breast carcinoma
    Marie Luise Brezniceanu
    Chemotherapeutisches Forschungsinstitut, Georg Speyer Haus, Paul Ehrlich Strasse 42 44, 60596 Frankfurt, Germany
    FASEB J 17:1295-7. 2003
    ..We found high HMGB1 protein levels in human primary breast carcinoma...
  54. ncbi High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo
    G Faraco
    Department of Preclinical and Clinical Pharmacology, University of Florence, Italy
    J Neurochem 103:590-603. 2007
    ..Together, data underscore the neuropathological role of nuclear HMGB1, and point to the protein as a mediator of post-ischemic brain damage...
  55. ncbi Immunogenic cancer cell death: a key-lock paradigm
    Antoine Tesniere
    INSERM, U848, F 94805 Villejuif, France
    Curr Opin Immunol 20:504-11. 2008
    ..Nonetheless, numerous details on the molecular events that define immunogenicity remain to be defined, both at the level of the dying cancer cells and at the level of the responding innate effectors...
  56. ncbi High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin
    De Yang
    Laboratory of Molecular Immunoregulation, Center for Cancer Research, and Basic Research Program, Rm 31 19 Bldg 560, 1050 Boyles Street, Frederick, MD 21702, USA
    J Leukoc Biol 81:59-66. 2007
    ..Based on its dual DC-attracting and -activating activities as well as its reported capacity to promote an antigen-specific immune response, we consider HMGB1 to have the properties of an immune alarmin...
  57. ncbi Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products
    Ingrid E Dumitriu
    Cancer Immunotherapy and Gene Therapy Program, Clinical Immunology Unit, H San Raffaele Scientific Institute, Milan, Italy
    J Immunol 174:7506-15. 2005
    ..The use of an ancient signal of necrosis, HMGB1, by dendritic cells to sustain their own maturation and for activation of T lymphocytes represents a profitable evolutionary mechanism...
  58. pmc Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice
    Evis Harja
    Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, New York 10032, USA
    J Clin Invest 118:183-94. 2008
    ..These data highlight unifying mechanisms whereby endothelial RAGE and its ligands mediate vascular and inflammatory stresses that culminate in atherosclerosis in the vulnerable vessel wall...
  59. ncbi High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivo
    Daniel J Antoine
    MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L693GE, UK
    Toxicol Sci 112:521-31. 2009
    ..Based on these findings, potential exists for the qualification and measurement of these proteins to further assist in vitro, in vivo, and clinical bridging in toxicological research...
  60. ncbi The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy
    Lionel Apetoh
    Institut Gustave Roussy IGR, Villejuif, France
    Immunol Rev 220:47-59. 2007
    ..This knowledge may be clinically exploited to predict the immunogenicity and hence the efficacy of chemotherapeutic regimens...
  61. ncbi Early release of HMGB-1 from neurons after the onset of brain ischemia
    Jianhua Qiu
    Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 28:927-38. 2008
    ..In conclusion, HMGB-1 is released early after ischemic injury from neurons and may contribute to the initial stages of the inflammatory response...
  62. pmc Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE
    Vilma Urbonaviciute
    Interdisciplinary Center of Clinical Research IZKF, research group N2, Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, University of Erlangen Nuremberg, Erlangen, Germany
    J Exp Med 205:3007-18. 2008
    ..In conclusion, HMGB1-nucleosome complexes activate antigen presenting cells and, thereby, may crucially contribute to the pathogenesis of SLE via breaking the immunological tolerance against nucleosomes/dsDNA...
  63. ncbi HMGB1 as a DNA-binding cytokine
    Ulf Andersson
    Department of Medicine, Rheumatology Research Unit, Karolinska Hospital, Stockholm, Sweden
    J Leukoc Biol 72:1084-91. 2002
    ....
  64. ncbi The "cytokine profile": a code for sepsis
    Luis Ulloa
    Center of Immunology and Inflammation, North Shore LIJ Research Institute, 350 Community Drive, Manhasset, NY 11030, USA
    Trends Mol Med 11:56-63. 2005
    ..Future clinical trials might define patient populations and therapeutic strategies according to the profile of expression of cytokines...
  65. ncbi Tail-mediated collapse of HMGB1 is dynamic and occurs via differential binding of the acidic tail to the A and B domains
    Katherine Stott
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, UK
    J Mol Biol 403:706-22. 2010
    ....
  66. ncbi HMGB1 loves company
    Marco E Bianchi
    San Raffaele University and San Raffaele Research Institute, Department of Genetics and Cell Biology, 20132 Milano, Italy
    J Leukoc Biol 86:573-6. 2009
    ..Thus, HMGB1 has dual activities, solo or in company; I speculate that this may serve our body's necessity to sacrifice or reconstruct tissues as required by the presence or absence of pathogens...
  67. ncbi Nucleocytoplasmic shuttling of HMGB1 is regulated by phosphorylation that redirects it toward secretion
    Ju Ho Youn
    Department of Microbiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon dong, Seodaemoon Gu, Seoul 120 752, Korea
    J Immunol 177:7889-97. 2006
    ..These data support the hypothesis that HMGB1 could be phosphorylated and that the direction of transport is regulated by phosphorylation of both NLS regions...
  68. pmc Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma
    Sandro Jube
    University of Hawai i Cancer Center, John A Burns School of Medicine, University of Hawai i, Honolulu, Hawaii 96813, USA
    Cancer Res 72:3290-301. 2012
    ....
  69. ncbi Activation of gene expression in human neutrophils by high mobility group box 1 protein
    Jong Sung Park
    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
    Am J Physiol Cell Physiol 284:C870-9. 2003
    ..These findings indicate that HMGB1 is an effective stimulus of neutrophil activation that can contribute to development of a proinflammatory phenotype in diseases characterized by excessively high levels of HMGB1...
  70. ncbi High-mobility group box 1 activates integrin-dependent homing of endothelial progenitor cells
    Emmanouil Chavakis
    Molecular Cardiology, Department of Internal Medicine III, J W Goethe University of Frankfurt, Frankfurt, Germany
    Circ Res 100:204-12. 2007
    ..These results may provide a platform for the development of novel therapeutic approaches to improve EPC homing...
  71. ncbi HMGB1 activates nuclear factor-κB signaling by RAGE and increases the production of TNF-α in human umbilical vein endothelial cells
    Zheng Gang Luan
    Department of Intensive Care Unit, The First Hospital, China Medical University, Bei Er Road 92, Shenyang 110001, Liaoning Province, China
    Immunobiology 215:956-62. 2010
    ..In the present study, we investigated the effects of HMGB1 on the activation of human umbilical vein endothelial cells (HUVECs) and defined pathways activated by HMGB1...
  72. pmc Inhibitor of NF-kappa B kinases alpha and beta are both essential for high mobility group box 1-mediated chemotaxis [corrected]
    Marianna Penzo
    Vita Salute San Raffaele University, School of Medicine, San Raffaele Scientific Institute, Milano, Italy
    J Immunol 184:4497-509. 2010
    ..Thus, proinflammatory HMGB1 chemotactic responses mechanistically require the differential collaboration of both IKK-dependent NF-kappaB signaling pathways...
  73. ncbi Upregulation of RAGE and its ligands in proliferative retinal disease
    Sophia I Pachydaki
    Department of Ophthalmology, College of Physician and Surgeons, Columbia University, New York, NY 10032, USA
    Exp Eye Res 82:807-15. 2006
    ..These findings suggest a role for the proinflammatory RAGE axis in the pathogenesis of proliferative retinal diseases...
  74. pmc Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein
    Hirotaka Kazama
    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO 631101, USA
    Immunity 29:21-32. 2008
    ..Similarly, blocking sites of oxidation in HMGB1 prevented tolerance induction by apoptotic cells. These results suggest that caspase-orchestrated mitochondrial events determine the impact of apoptotic cells on the immune response...
  75. pmc Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation
    Roberta Palumbo
    Department of Molecular Biology and Functional Genomics, San Raffaele Research Institute, Milan, Italy
    J Cell Biol 164:441-9. 2004
    ..Although the role of endogenous HMGB1 in the reconstruction of dystrophic muscle remains to be clarified, injected HMGB1 may be used to promote tissue regeneration...
  76. pmc HMGB1 induces human lung endothelial cell cytoskeletal rearrangement and barrier disruption
    Rachel K Wolfson
    University of Chicago, Department of Pediatrics, IL, USA
    Microvasc Res 81:189-97. 2011
    ..These studies add to the understanding of HMGB1-induced inflammatory events and vascular barrier disruption and offer the potential for clinical intervention in sepsis-induced ALI...
  77. ncbi Glycyrrhizic acid affords robust neuroprotection in the postischemic brain via anti-inflammatory effect by inhibiting HMGB1 phosphorylation and secretion
    Seung Woo Kim
    Department of Anatomy and Center for Advanced Medical Education by BK21 project, Inha University School of Medicine, Inchon, Republic of Korea
    Neurobiol Dis 46:147-56. 2012
    ....
  78. pmc High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism
    Federico Biscetti
    Laboratory of Vascular Biology and Genetics, Department of Medicine, A Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy
    Diabetes 59:1496-505. 2010
    ..To test the hypothesis that HMGB1 enhances ischemia-induced angiogenesis in diabetes, we administered HMGB1 protein in a mouse hind limb ischemia model using diabetic mice.
  79. ncbi High-mobility group box protein 1 neutralization reduces development of diet-induced atherosclerosis in apolipoprotein e-deficient mice
    Peter Kanellakis
    BakerIDI Heart and Diabetes Institute, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
    Arterioscler Thromb Vasc Biol 31:313-9. 2011
    ..We investigated its role in the development of atherosclerosis in ApoE-/- mice...
  80. ncbi Effects of hyperglycemia and insulin therapy on high mobility group box 1 in endotoxin-induced acute lung injury in a rat model
    Satoshi Hagiwara
    Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, Oita, Japan
    Crit Care Med 36:2407-13. 2008
    ....
  81. ncbi High-mobility group box 1 (HMGB1) as a master regulator of innate immunity
    Alessandra Castiglioni
    Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute and Vita Salute San Raffaele University, DIBIT 3A1, Via Olgettina 58, 20132 Milan, Italy
    Cell Tissue Res 343:189-99. 2011
    ..Evidence suggests that HMGB1 acts as a key molecule of innate immunity, downstream of persistent tissue injury, orchestrating inflammation, stem cell recruitment/activation, and eventual tissue remodeling...
  82. ncbi HMGB1 in systemic lupus Erythematosus: Its role in cutaneous lesions development
    D A Abdulahad
    Department of Rheumatology and Clinical Immunology, University Medical Center, University of Groningen, The Netherlands
    Autoimmun Rev 9:661-5. 2010
    ..In this review the general characteristics and activities of HMGB1 are highlighted and its role in SLE will be discussed with special attention to its involvement in the pathogenesis of skin lesions...
  83. ncbi High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes
    Ju Ho Youn
    Department of Microbiology, Brain Korea 21 Project for Medical Science, National Core Research Center for Nanomedical Technology, Yonsei University College of Medicine, Seoul, Republic of Korea
    J Immunol 180:5067-74. 2008
    ..Thus, we propose that HMGB1 plays an important role in Gram-negative sepsis by catalyzing movement of LPS monomers from LPS aggregates to CD14 to initiate a TLR4-mediated proinflammatory response...
  84. ncbi Molecular interactions between dying tumor cells and the innate immune system determine the efficacy of conventional anticancer therapies
    Lionel Apetoh
    Institut National de la Sante et de la Recherche Medicale, U805, Villejuif, France
    Cancer Res 68:4026-30. 2008
    ..These data suggests that HMGB1- and TLR4-dependent immune responses elicited by conventional cancer treatment may increase the probability to achieve a durable therapeutic success...
  85. ncbi The role of high mobility group box1 in pulmonary fibrosis
    Naoki Hamada
    Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
    Am J Respir Cell Mol Biol 39:440-7. 2008
    ..BALF HMGB1 levels were significantly increased in IPF and HP compared with control subjects. HMGB1 protein was predominantly detected in inflammatory cells and hyperplasic epithelial cells in IPF...
  86. ncbi Intraocular expression and release of high-mobility group box 1 protein in retinal detachment
    Noboru Arimura
    Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
    Lab Invest 89:278-89. 2009
    ..Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response...
  87. pmc Expression of high-mobility groups box-1/receptor for advanced glycation end products/osteopontin/early growth response-1 pathway in proliferative vitreoretinal epiretinal membranes
    Ahmed M Abu El-Asrar
    Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
    Mol Vis 17:508-18. 2011
    ..We investigated the expression of the components of this pathway in proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR) epiretinal membranes...
  88. ncbi Osteopontin expression is required for myofibroblast differentiation
    Yair Lenga
    Faculty of Dentistry, University of Toronto, 124 Edward St, Toronto, Ontario M5G 1G6, Canada
    Circ Res 102:319-27. 2008
    ..analysis of proteins in focal adhesions formed on collagen type I beads revealed an enrichment of HMGB1 protein in wild-type cells, whereas HMGB1 was not detected in OPN-null cells...
  89. ncbi Cutting edge: extracellular high mobility group box-1 protein is a proangiogenic cytokine
    Stefania Mitola
    Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brecia, Brescia, Italy
    J Immunol 176:12-5. 2006
    ..Taken together, the data identify HMGB1/RAGE interaction as a potent proangiogenic stimulus...
  90. pmc High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease
    David S Pisetsky
    Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, USA
    Arthritis Res Ther 10:209. 2008
    ..New approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling...
  91. pmc Angiogenetic signaling through hypoxia: HMGB1: an angiogenetic switch molecule
    Claudia Schlueter
    Center for Human Genetics, University of Bremen, Leobenerstr ZHG, D 28359 Bremen, Germany
    Am J Pathol 166:1259-63. 2005
    ..Thus, this is the first report showing strong evidence for HMGB1-induced sprouting of endothelial cells...
  92. ncbi Ethyl pyruvate induces necrosis-to-apoptosis switch and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells
    Sung Chul Lim
    Research Center for Resistant Cells, Department of Pathology, College of Medicine, Chosun University, Gwangju 501 759, Korea
    Int J Mol Med 20:187-92. 2007
    ....
  93. pmc High mobility group box protein 1 (HMGB1)-partner molecule complexes enhance cytokine production by signaling through the partner molecule receptor
    Hulda Sigridur Hreggvidsdottir
    Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden
    Mol Med 18:224-30. 2012
    ..Elucidating HMGB1 receptor usage in processes where HMGB1 acts alone or in complex with other molecules is essential for the understanding of basic HMGB1 biology and for designing HMGB1-targeted therapies...
  94. ncbi High mobility group box protein-1 inhibits microglial Abeta clearance and enhances Abeta neurotoxicity
    Kazuyuki Takata
    Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan
    J Neurosci Res 78:880-91. 2004
    ..These results suggest that HMGB1 released from dying neurons may inhibit microglial Abeta42 clearance and enhance the neurotoxicity of Abeta42. HMGB1 may thus be another target in the investigation of a therapeutic strategy for AD...
  95. pmc Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome
    Joseph A Duncan
    Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Immunol 182:6460-9. 2009
    ..Our findings indicate that activation of NLRP3-mediated inflammatory response pathways is an important venue associated with host response and pathogenesis of N. gonorrhoeae...
  96. pmc Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release
    Emilie Venereau
    Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy
    J Exp Med 209:1519-28. 2012
    ..Thus, HMGB1 orchestrates both key events in sterile inflammation, leukocyte recruitment and their induction to secrete inflammatory cytokines, by adopting mutually exclusive redox states...
  97. pmc Prognostic value of HMGB1 overexpression in resectable gastric adenocarcinomas
    Guoqiang Bao
    Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi an 710038, China
    World J Surg Oncol 8:52. 2010
    ..In the present study, HMGB1 overexpression and its correlation with the clinicopathologic characteristics and recurrence-free survival were evaluated in gastric adenocarcinomas...
  98. ncbi Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac C-kit+ cell proliferation and differentiation
    Federica Limana
    Laboratorio di Patologia Vascolare, Istituto Dermopatico dell Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy
    Circ Res 97:e73-83. 2005
    ..Thus, HMGB1 appears to be a potent inducer of myocardial regeneration following myocardial infarction...
  99. ncbi High-mobility group box 1 promotes early acute allograft rejection by enhancing IL-6-dependent Th17 alloreactive response
    Lihua Duan
    Laboratory of Transplantation, Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Lab Invest 91:43-53. 2011
    ....
  100. ncbi Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance
    Yong Liu
    Department of Otolaryngology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China
    Eur J Cancer 46:3007-15. 2010
    ..The aim of the present investigation was to analyse HMGB1 protein expression in both SCCHN tissue and cell levels and to assess its prognostic significance in SCCHN.
  101. pmc High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus
    Deena A Abdulahad
    Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, PO Box 30 001, 9700 RB Groningen, The Netherlands
    Arthritis Res Ther 13:R71. 2011
    ..In this study we determined levels of HMGB1 and anti-HMGB1 in SLE patients in comparison to healthy controls (HC) and analysed their relation with disease activity...

Research Grants68

  1. Regulation of LPS-mediated HMGB1 Release by Poly (ADP-ribose) Polymerase-1
    RAJESH K ANEJA; Fiscal Year: 2013
    ..Additional studies will be performed to determine the therapeutic window for use of PARP-1 inhibitors in murine sepsis. ..
  2. CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGS
    Stephen J Lippard; Fiscal Year: 2013
    ..The knowledge acquired will be used to design, synthesize, and evaluate new anticancer drug candidates for targeting and destroying tumors. ..
  3. MOLECULAR BIOLOGY OF HEMORRHAGIC SHOCK
    Timothy R Billiar; Fiscal Year: 2013
    ..Based on our progress thus far, we are fully confident that our approach will continue to lead to productive collaboration and effective testing of a novel and important hypotheses. ..
  4. The Role of Sex in Self Antigen Generation in SLE
    David Stephen Pisetsky; Fiscal Year: 2010
    ..Understanding these mechanisms should lead to new approaches to diagnosis and treatment as well as the development of novel biomarkers relevant to both lupus and other immune-mediated diseases. ..
  5. HMG in Post Operative and Traumatic Stress
    Kevin J Tracey; Fiscal Year: 2013
    ....
  6. DAMP-RAGE Signaling and Fetal Injury in Inflammation-Induced Preterm Birth
    Irina A Buhimschi; Fiscal Year: 2013
    ..abstract_text> ..
  7. Regulation of HMGB1 Release in Endotoxemia
    Haichao Wang; Fiscal Year: 2013
    ....
  8. MECHANISMS OF AUTOIMMUNITY IN SLE
    David Stephen Pisetsky; Fiscal Year: 2013
    ..Successful completion of these experiments will provide new insights in the pathogenic role in SLE of nuclear molecules in the form of microparticles as well as provide new biomarkers and potential targets of therapy. ..
  9. Endogenous regulators of inflammation in liver ischemia/reperfusion
    Allan Tsung; Fiscal Year: 2013
    ..g. myocardial infarction and cerebral ischemia). ..
  10. The role of cell death in Lupus Nephritis
    Roberto Caricchio; Fiscal Year: 2013
    ..The rationale for our project is that a better understanding of the pathways regulating the tissue damage in lupus GN pathophysiologies in males and females will lead to a tailored and better treatment for each gender. ..
  11. HMGB1 and neutrophil efferocytosis.
    JAROSLAW WALDEMAR ZMIJEWSKI; Fiscal Year: 2012
    ....
  12. Metastatic protein network in BRAFV600E positive human thyroid cancers
    Carmelo Nucera; Fiscal Year: 2013
    ....
  13. Epigenetics of Severe Systemic Inflammation
    CHARLES EMORY MCCALL; Fiscal Year: 2013
    ..From these results, novel therapeutic interventions or preventions may be designed to improve the poor outcomes associated with SSI. ..
  14. The Role of HMGB1 in Acute Lung Injury-Induced Endothelial Cell Permeability
    Rachel K Wolfson; Fiscal Year: 2012
    ..This proposal aims to define the mechanism by which HMGB1 disrupts lung endothelial cell barrier function and contributes to ALI, opening the door for potential therapeutic intervention in the future. ..
  15. HO1 AND TLR4 IN LIVER ISCHEMIA/REPERFUSION INJURY IN TRANSPLANT RECIPIENTS
    Jerzy W Kupiec-Weglinski; Fiscal Year: 2013
    ..By modulating oxidant (HO-1 siRNA) and inflammatory (anti-HMGB1/rHMGB1) responses, we will study the regulatory function of Nrf2 upon (i) HO-1 vs (ii) TLR4 signaling pathways during IRI in OLT recipients. ..
  16. Thrombomodulin Receptors on Immune Cells
    John Morser; Fiscal Year: 2013
    ..In addition, delineating the mechanism by which TM modulates DCs and other immune cells would allow identification of alternative targets and assays by which drugs for inflammatory diseases could be discovered. ..
  17. Mechanisms of Novel Herbal Therapies for Sepsis.
    Haichao Wang; Fiscal Year: 2013
    ....
  18. Targeting host response to DAMP for therapy of Rheumatoid Arthritis
    Dexing Fang; Fiscal Year: 2011
    ....
  19. CaMK: central regulators of the inflammatory response to surgical sepsis
    MATTHEW RANDALL ROSENGART; Fiscal Year: 2013
    ....
  20. Critical roles of endogenous TLR signaling in driving Th17 effector responses
    JOSEPH MICHAEL REYNOLDS; Fiscal Year: 2013
    ..abstract_text> ..
  21. The role of HMGB-1 and innate immunity in promoting angiogenesis after ischemia
    Ulka Sachdev; Fiscal Year: 2013
    ..The second aim is to determine the function of HMGB-1 and autophagy in skeletal muscle angiogenesis in vivo. The third aim is to identify a role for the TLRs in mediating the angiogenic actions of HMGB1. ..
  22. Immunity in alcoholic hepatitis.
    Zhang Xu Liu; Fiscal Year: 2013
    ....
  23. Mechanism of action and therapeutic potential of HMGB1 A box in sepsis
    Huan Yang; Fiscal Year: 2013
    ..In structure-function analyses, we observed that A box (amino acids 1-85 on HMGB1 protein), has an antagonistic effect to HMGB1...
  24. Central cholinergic regulation of inflammation
    VALENTIN ATANASSOV PAVLOV; Fiscal Year: 2013
    ..The effect of galantamine on the systemic cytokine response and survival and its dependence on specific brain dysfunction will be evaluated in therapeutic settings. ..
  25. Innate Immune Response and Intestinal Inflammation
    Sang Hoon Rhee; Fiscal Year: 2010
    ..During the time of the award I will continue basic research to study liver fibrosis with an emphasis on "translational medicine" - taking the latest research and translating it into clinical therapies. ..
  26. Mechansim of activation of innate immunity by ISS-DNA
    Wen Ming Chu; Fiscal Year: 2013
    ....
  27. The Role of HMGB1 in the Pathogenesis of Mesothelioma
    Haining Yang; Fiscal Year: 2013
    ..Finally, we will determine the effects of HMGB1 and HMGB1 inhibitors on the migration, invasion and colony formation of MM cells and assess the potential of inhibiting HMGB1 for MM therapy. ..
  28. FADD Signaling in Cancer Cells
    Andrew M Thorburn; Fiscal Year: 2013
    ....
  29. Blocking toll-like receptor 4 signaling as therapy in hepatic fibrosis
    BERND G SCHNABL; Fiscal Year: 2013
    ..During the time of the award I will continue basic research to study liver fibrosis with an emphasis on "translational medicine" - taking the latest research and translating it into clinical therapies. ..
  30. AMPK activation and acute lung injury
    JAROSLAW WALDEMAR ZMIJEWSKI; Fiscal Year: 2013
    ..abstract_text> ..
  31. The structural basis of nucleic acid recognition by Toll-like receptors
    Yorgo Modis; Fiscal Year: 2013
    ....
  32. Cartilage Innate Immunity in Osteoarthritis
    RU BRYAN; Fiscal Year: 2013
    ..There is a pressing need to identify mediators beyond IL-1 that drive OA progression, in order to develop true and effective disease modifying treatment of this disease. ..
  33. CD200 as a monocyte/macrophage switch for brain repair after stroke
    Kazuhide Hayakawa; Fiscal Year: 2013
    ..I will learn the biomaterials and in vivo optical imaging tools from my mentor/consultants. My long term goal is to grow and build my independent lab based on the theme of manipulating inflammation for brain repair. ..
  34. The role of innate immunity in idiopathic pulmonary arterial hypertension
    Philip M Bauer; Fiscal Year: 2012
    ..abstract_text> ..
  35. TLR4 in obesity-driven liver cancer
    Jorge Matias Caviglia; Fiscal Year: 2013
    ..Results from the proposed studies will provide a better understanding of how obesity promotes liver cancer and may point to targets for treatment. ..
  36. Role of autophagy in tumor cell death
    Andrew M Thorburn; Fiscal Year: 2013
    ....
  37. Structure Function Studies of DNA Mismatch Repair
    Dorothy A Erie; Fiscal Year: 2010
    ....
  38. IMMUNOGLOBULIN AND T CELL RECEPTOR GENE ASSEMBLY
    David G Schatz; Fiscal Year: 2013
    ..abstract_text> ..
  39. Epithelial Cell-Derived IL-1-alpha as a Novel Danger Signal in IBD Pathogenesis
    Eleni Stylianou; Fiscal Year: 2013
    ....
  40. Toll-Like Receptor Signaling in Hepatic Fibrogenesis
    Robert F Schwabe; Fiscal Year: 2012
    ....
  41. HMGB1 and Traumatic Brain Injury
    Krishnan M Dhandapani; Fiscal Year: 2013
    ..The results of these studies may support the future development of novel therapeutics directed against this pathway to limit neurological injury following head trauma. ..
  42. Targeting DAMPs in Alcoholic Hepatitis
    Robert F Schwabe; Fiscal Year: 2013
    ..We anticipate to unravel the contribution of DAMPs to hepatic and systemic inflammation in AH, and to establish select DAMPs and their receptors as "druggable" targets in AH. ! ..
  43. Role of Receptor for Advanced Glycation End Product (RAGE) Pathway in Brain Tumor
    Behnam Badie; Fiscal Year: 2013
    ..abstract_text> ..
  44. Molecular Subtypes for Targeted Therapies in Alcoholic Hepatitis
    Ramon Bataller; Fiscal Year: 2013
    ..We anticipate that the systematic approach and translational nature of this consortium will advance the understanding of AH, and provide novel approaches for its prevention and treatment. ..
  45. Targeting HMGB1-mediated Autophagy in Cancer Therapy
    Daolin Tang; Fiscal Year: 2013
    ..These studies will provide new insights into HMGB1 signaling and the role of autophagy in tumor therapy. This deeper understanding will be used to improve the effectiveness of existing pancreatic cancer therapies. ..
  46. Analysis of TLR agonist treated tumor cells
    Robert A Kurt; Fiscal Year: 2012
    ..The results from this project therefore may open the door to new strategies for the treatment of patients with cancer. ..
  47. Role of NLRP3-inflammasome in alum's adjuvanticity
    FABIO C RE; Fiscal Year: 2013
    ..Necrotic cells are known to release danger signals, such as the HMGB1 protein, that possess adjuvant ability...
  48. Protective mechanisms of ischemic postconditioning
    Heng Zhao; Fiscal Year: 2013
    ..Specific Aim 3. To examine the protective effects of the Akt/PRAS40 pathway on the pro-inflammatory response of HMGB1 and Cox-2, and the galectin-9/Tim-3 inflammatory pathway. ..
  49. Astrocyte-endothelial crosstalk after cerebral ischemia and hemorrhage
    Eng H Lo; Fiscal Year: 2013
    ..Dissecting these cell-cell signaling pathways may lead to new therapeutic approaches for promoting functional recovery in patients after ischemic and hemorrhagic strokes. ..
  50. HMGB1-Derived Peptides As Vaccine Adjuvants
    Bradley T Messmer; Fiscal Year: 2012
    ..These studies will provide the basis for testing its broad applicability to other clinically relevant antigens. ..
  51. MRSA Activation of Human Keratinocyte Signaling
    Alice S Prince; Fiscal Year: 2013
    ..This project will determine if keratinocyte signaling, which we postulate is responsible for much of the pathology evoked by these organisms, provides therapeutic targets to prevent staphylococcal infection. ..
  52. Regulation of Immunity by Dead Cells
    THOMAS ALMON FERGUSON; Fiscal Year: 2012
    ..abstract_text> ..
  53. CD24 in Cancer Resistance and Immunotherapy
    Yang Liu; Fiscal Year: 2013
    ..To understand the molecular basis for the opposite function of CD24, we will carry out a thorough structural analysis of saccharide associated with DC and T cells by state-of-art mass-spectrometry. ..
  54. Ductal preservation solutions and quantity and quality of isolated human islets
    MARLON FRANTZ LEVY; Fiscal Year: 2012
    ..This proposed study will focus on identifying the best ductal preservation solution in order to maximize the quantity and quality of isolated islets. ..
  55. HIV-Induced Immune Activation in Humanized MIce
    MANJUNATH NARASIMHA SWAMY; Fiscal Year: 2013
    ..In the second aim we will test if silencing HMGB1 or downstream cytokines by targeted delivery of siRNA to macrophages and dendritic cells can reduce immune activation and disease progression in infected mice. ..
  56. Checkpoints of Host Response to Cellular Injuries
    Yang Liu; Fiscal Year: 2013
    ..Since CD24 defects block the development of autoimmune diseases, our study provides a molecular basis linking inflammation to immunity to cancer or infection without provoking autoimmune diseases. ..
  57. Stress, Glucocorticoids and Neuroinflammatory Priming
    Steven F Maier; Fiscal Year: 2013
    ..Thus, the present research may lead to a reconceptualization of stress/GCs as neuroinflammatory predisposing factors in the etiology of psychiatric disorders (i.e. major depression, PTSD). ..
  58. Biomarker and Metabolomic Investigations in ALI
    Annette M Esper; Fiscal Year: 2013
    ..The long- term goal is to develop an affordable approach that can be used for predicting disease susceptibility, diagnosis, risk stratification, response to therapy and prognosis. ..
  59. HMGB1/2 and Cellular Response to Fraudulent Nucleosides
    Evgeny Krynetskiy; Fiscal Year: 2007
    ..abstract_text> ..
  60. Mechanism of PCNA-dependent 5'->3' Mismatch Excision
    Guo Min Li; Fiscal Year: 2010
    ..g., the EXO1 gene, are associated with cancer development, identifying the components required for the novel 5'excision pathway will provide new diagnostic markers for HNPCC and other MMR deficient cancer syndromes. ..
  61. Induction of Th 17 immunity by different cutaneous dendritic cell populations
    Alicia R Mathers; Fiscal Year: 2011
    ..Therefore, a better understanding of how Th17 immunity is initiated and sustained will have a positive impact on rational vaccine design and for the development of new therapeutic targets for cutaneous autoimmune diseases. ..
  62. Ethyl Pyruvate: A Novel Treatment for Sepsis
    RUSSELL DELUDE; Fiscal Year: 2006
    ..Achieving a better understanding of the mechanisms responsible for the anti-inflammatory and therapeutic effects of EP may permit identification of novel cellular pathways involved in the innate immune response. ..
  63. Sepsis syndrome and adenosine A2A receptor activation
    WILLIAM SCHELD; Fiscal Year: 2007
    ..abstract_text> ..
  64. RAGE and a Novel Tumor Axis
    Ann Schmidt; Fiscal Year: 2005
    ....
  65. RAGE and modulation of tumor properties
    Emina Huang; Fiscal Year: 2006
    ..A range of tools will be employed in order to accomplish these goals, both in in vitro assay systems, and in vivo, using RAGE null mice and a murine model of familial adenomatous polyposis (FAP). ..
  66. The role of HMGB1-RAGE in hepatic fibrosis
    Zaki Megeed; Fiscal Year: 2006
    ..abstract_text> ..
  67. A Filter to Remove HMGB1
    YEHUDA TAMARI; Fiscal Year: 2009
    ..We propose to bring to the clinical market an extracorporeal system that removes HMGB1 protein from the plasma of septic patients unresponsive to standard treatment...
  68. Novel Carboxylated Glycans in Cell Adhesion
    Hudson Freeze; Fiscal Year: 2006
    ....