interleukin 6 receptors

Summary

Summary: Receptors present on T cells, mitogen-activated B cells, peripheral monocytes, and some macrophage- and B cell-derived tumor cell types. The receptor is a strongly glycosylated protein of 80 kDa and a length of 468 amino acids. (Ibelgaufts, Dictionary of Cytokines, 1995)

Top Publications

  1. ncbi Interleukin-6 and its receptor in cancer: implications for translational therapeutics
    David S Hong
    Phase I Program, Division of Cancer Medicine, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 110:1911-28. 2007
  2. ncbi Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation
    S M Hurst
    Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, United Kingdom
    Immunity 14:705-14. 2001
  3. ncbi IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation
    Gilles Kaplanski
    INSERM U387, Hopital Sainte Marguerite, 270 Boulevard de Sainte Marguerite, 13009 Marseille, France
    Trends Immunol 24:25-9. 2003
  4. pmc IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial
    P Emery
    Leeds Teaching Hospitals Trust, University of Leeds, Leeds, UK
    Ann Rheum Dis 67:1516-23. 2008
  5. ncbi Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug the
    Mark C Genovese
    Division of Rheumatology, Stanford University Medical Center, Palo Alto, California 94304, USA
    Arthritis Rheum 58:2968-80. 2008
  6. ncbi The soluble interleukin 6 receptor: mechanisms of production and implications in disease
    S A Jones
    Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, UK
    FASEB J 15:43-58. 2001
  7. ncbi Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
    T Taga
    Division of Immunology, Osaka University, Japan
    Cell 58:573-81. 1989
  8. ncbi Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    J Leukoc Biol 80:227-36. 2006
  9. ncbi Interleukin-6 and its receptor: from bench to bedside
    Jürgen Scheller
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, 24098 Kiel, Germany
    Med Microbiol Immunol 195:173-83. 2006
  10. pmc Principles of interleukin (IL)-6-type cytokine signalling and its regulation
    Peter C Heinrich
    Institut fur Biochemie, RWTH Aachen, Universitatsklinikum, Pauwelsstrasse 30, D 52074 Aachen, Germany
    Biochem J 374:1-20. 2003

Research Grants

Detail Information

Publications249 found, 100 shown here

  1. ncbi Interleukin-6 and its receptor in cancer: implications for translational therapeutics
    David S Hong
    Phase I Program, Division of Cancer Medicine, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer 110:1911-28. 2007
    ..Therapeutic targeting of IL-6 and its receptor in cancer has strong biologic rationale, and there is preliminary evidence suggesting that targeting of the IL-6 system may be beneficial in the treatment of cancer...
  2. ncbi Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation
    S M Hurst
    Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, United Kingdom
    Immunity 14:705-14. 2001
    ....
  3. ncbi IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation
    Gilles Kaplanski
    INSERM U387, Hopital Sainte Marguerite, 270 Boulevard de Sainte Marguerite, 13009 Marseille, France
    Trends Immunol 24:25-9. 2003
    ..Furthermore, we suggest that the first Toll-like family receptors that arose in evolution might have acted in both development and immunity by recognizing the degradation of endogenous macromolecules...
  4. pmc IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial
    P Emery
    Leeds Teaching Hospitals Trust, University of Leeds, Leeds, UK
    Ann Rheum Dis 67:1516-23. 2008
    ..The phase III RADIATE study examined the efficacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist therapy...
  5. ncbi Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug the
    Mark C Genovese
    Division of Rheumatology, Stanford University Medical Center, Palo Alto, California 94304, USA
    Arthritis Rheum 58:2968-80. 2008
    ..To examine the efficacy and safety of the humanized anti-interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA)...
  6. ncbi The soluble interleukin 6 receptor: mechanisms of production and implications in disease
    S A Jones
    Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, UK
    FASEB J 15:43-58. 2001
    ..We want to convey, therefore, that when thinking about the inflammatory capability of IL-6, it is essential to consider not only the action of IL-6 itself, but also the effect sIL-6R may have on cellular processes...
  7. ncbi Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130
    T Taga
    Division of Immunology, Osaka University, Japan
    Cell 58:573-81. 1989
    ..These findings indicate that the complex of IL-6 and IL-6-R can interact with a non-ligand-binding membrane glycoprotein, gp130, extracellularly and can provide the IL-6 signal...
  8. ncbi Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, D 24098 Kiel, Germany
    J Leukoc Biol 80:227-36. 2006
    ..The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed...
  9. ncbi Interleukin-6 and its receptor: from bench to bedside
    Jürgen Scheller
    Institut fur Biochemie, Christian Albrechts Universitat zu Kiel, Olshausenstr 40, 24098 Kiel, Germany
    Med Microbiol Immunol 195:173-83. 2006
    ..These designer cytokines have been shown to be extremely useful to in therapeutic applications ranging from the long-term culture of stem cells and enhancing liver regeneration up to the blockade of chronic inflammation and cancer...
  10. pmc Principles of interleukin (IL)-6-type cytokine signalling and its regulation
    Peter C Heinrich
    Institut fur Biochemie, RWTH Aachen, Universitatsklinikum, Pauwelsstrasse 30, D 52074 Aachen, Germany
    Biochem J 374:1-20. 2003
    ..Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed...
  11. ncbi Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate
    R N Maini
    Kennedy Institute of Rheumatology Division, Imperial College, London, UK
    Arthritis Rheum 54:2817-29. 2006
    ....
  12. ncbi Inhibition of IL-6 for the treatment of inflammatory diseases
    Norihiro Nishimoto
    Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, 1 3 Yamada oka, Suita City, Osaka, 565 0871, Japan
    Curr Opin Pharmacol 4:386-91. 2004
    ..Humanized anti-IL-6 receptor antibody has been developed as a therapeutic agent for these diseases, and therapeutic benefits have been revealed in clinical studies...
  13. ncbi Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy
    N Nishimoto
    Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Suita City, Osaka, Japan
    Blood 95:56-61. 2000
    ..Blood. 2000;95:56-61)..
  14. pmc Anti-interleukin 6 receptor antibody treatment in rheumatic disease
    N Nishimoto
    Department of Medical Science I, School of Health and Sport Sciences, Osaka University, 2 1 Yamada oka, Suita City, Osaka 565 0871, Japan
    Ann Rheum Dis 59:i21-7. 2000
    ..In this review, the new therapeutic strategy for Castleman's disease and RA using humanized antibody to human IL6 receptor, MRA, is discussed...
  15. ncbi Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils
    Athena Chalaris
    Department of Biochemistry, Christian Albrechts University, Kiel, Germany
    Blood 110:1748-55. 2007
    ....
  16. ncbi Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor
    Kamilla Malinowska
    Department of Urology, Innsbruck Medical University, Anichstrasse 35, A 6020 Innsbruck, Austria
    Endocr Relat Cancer 16:155-69. 2009
    ..Taken together, data in the present study demonstrate that IL-6 may cause growth of androgen receptor-positive tumours in vitro and in vivo through activation of the androgen receptor...
  17. ncbi Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis
    S F Shariat
    Baylor Prostate Center, Scott Department of Urology, Baylor College of Medicine and Methodist Hospital, Houston, Texas, USA
    Urology 58:1008-15. 2001
    ....
  18. ncbi Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease
    Norihiro Nishimoto
    Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, 1 3 Yamada oka, Suita, Osaka 565 0871, Japan
    Blood 106:2627-32. 2005
    ..Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD...
  19. ncbi Characterization of the role of IL-6 in the progression of prostate cancer
    T D Chung
    Department of Radiation and Cellular Oncology, University of Chicago, Illinois, USA
    Prostate 38:199-207. 1999
    ..In the present study, we investigated the expression of members of the IL-6 supergene family and related cytokines and the potential role of IL-6 in prostate cancer growth regulation...
  20. ncbi JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of SOX9 expression
    Florence Legendre
    Laboratoire de Biochimie du Tissu Conjonctif, Faculte de Medecine, 14032 Caen Cedex, France
    J Biol Chem 278:2903-12. 2003
    ..These IL-6 effects might contribute to the phenotype loss of chondrocytes in joint diseases and the alteration of articular cartilage associated with this pathology...
  21. ncbi Interleukin-6 is a growth factor for nonmalignant human plasmablasts
    G Jego
    , Institut de Biologie, Nantes, France
    Blood 97:1817-22. 2001
    ..Finally, IL-6 enhanced the proliferation (2-fold increase) of IL-2-generated plasmablasts. In conclusion, the data indicate that IL-6 is a growth factor for nonmalignant human plasmablasts...
  22. ncbi Characterization of anti-mouse interleukin-6 receptor antibody
    Makoto Okazaki
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co Ltd, 135 Komakado 1 chome, Gotemba shi, Shizuoka 412 8513, Japan
    Immunol Lett 84:231-40. 2002
    ..These lines of evidence demonstrate that MR16-1 is useful to investigate the physiological and pathological roles of IL-6 and sIL-6R in mice...
  23. ncbi The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer
    Michael W Kattan
    Scott Department of Urology, Baylor College of Medicine, 6535 Fannin St, Houston, TX 77030, USA
    J Clin Oncol 21:3573-9. 2003
    ....
  24. ncbi Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo
    R Atreya
    Lab of Immunology and Section Pathophysiology, I Medical Clinic, University of Mainz, 55131 Mainz, Germany
    Nat Med 6:583-8. 2000
    ..These data indicate that a pathway of T-cell activation driven by IL-6-sIL-6R contributes to the perpetuation of chronic intestinal inflammation. Specific targeting of this pathway may be a promising new approach for the treatment of CD...
  25. ncbi Molecular cloning and expression of an IL-6 signal transducer, gp130
    M Hibi
    Division of Immunology, Osaka University, Japan
    Cell 63:1149-57. 1990
    ..A cloned gp130 could associate with a complex of IL-6 and soluble IL-6-R and transduce the growth signal when expressed in a murine IL-3-dependent cell line...
  26. pmc Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition t
    Norihiro Nishimoto
    Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
    Mod Rheumatol 19:12-9. 2009
    ..All serious adverse events improved by adequate treatment. Tocilizumab monotherapy was well tolerated and provided an excellent clinical benefit in active RA patients with an inadequate response to low dose MTX...
  27. pmc The paradigm of IL-6: from basic science to medicine
    Tetsuji Naka
    Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan
    Arthritis Res 4:S233-42. 2002
    ..On the basis of the findings, a new therapeutic approach to block the IL-6 signal using humanized anti-IL-6R antibody for rheumatoid arthritis, Castleman's disease, and multiple myeloma has been attempted...
  28. pmc Interleukin-6 and soluble interleukin-6 receptor levels as markers of disease extent and prognosis in neuroblastoma
    Rachel A Egler
    Department of Pediatrics, Texas Children s Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA
    Clin Cancer Res 14:7028-34. 2008
    ..To explore the relationships between interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) levels and disease extent and clinical outcome in childhood neuroblastoma...
  29. ncbi Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites
    Yasmin H Hamid
    Steno Diabetes Center, Hagedorn Research Institute, Gentofte, Copenhagen, Denmark
    Diabetes 53:3342-5. 2004
    ..In conclusion, the Asp358Ala polymorphism of the IL6R associates with type 2 diabetes in Danish whites...
  30. pmc 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling
    W Somers
    Small Molecule Drug Discovery, Genetics Institute, Inc, Cambridge, MA 02140, USA
    EMBO J 16:989-97. 1997
    ..Based on this model, we predict a fourth binding site on IL-6, a low affinity IL-6-IL-6 interaction, which may be necessary for the sequential assembly of a functional hexameric IL-6 receptor complex...
  31. ncbi In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of hIL-6-transgenic mice with a hIL-6 receptor antagonist
    F De Benedetti
    Dipartimento di Scienze Pediatriche, Instituto di Ricerca e Cura a Carattere Scientifico Policlinico San Matteo, Universita' degli Studi di Pavia, Pavia, Italy
    J Immunol 166:4334-40. 2001
    ..Immunization with Sant1 could therefore represent a novel and simple therapeutic approach for the specific neutralization of IL-6 in humans...
  32. ncbi The IL-6/sIL-6R complex as a novel target for therapeutic approaches
    Stefan Rose-John
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Kiel, Germany
    Expert Opin Ther Targets 11:613-24. 2007
    ..An optimised variant of the recently described fusion protein sgp30Fc is now heading towards its clinical evaluation...
  33. ncbi IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae
    Py Palmqvist
    Department of Oral Cell Biology, Umea University, Umea, Sweden
    J Immunol 169:3353-62. 2002
    ....
  34. ncbi Interleukin 6 and its receptor: ten years later
    T Hirano
    Department of Molecular Oncology, Osaka University Medical School, Japan
    Int Rev Immunol 16:249-84. 1998
    ..The deregulated expression of IL-6 and its receptor is involved in a variety of diseases...
  35. ncbi Technology evaluation: MRA, Chugai
    Changhai Ding
    Menzies Centre for Population Health Research, University of Tasmania, 17 Liverpool Street, Hobart, 7000 TAS, Australia
    Curr Opin Mol Ther 5:64-9. 2003
    ..MRA is currently undergoing phase II clinical trials for these indications...
  36. pmc Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells
    L Snyers
    Department of Virology, Institut Pasteur du Brabant, Brussels, Belgium
    Proc Natl Acad Sci U S A 87:2838-42. 1990
    ....
  37. ncbi Do we need new treatment that goes beyond tumor necrosis factor blockers for rheumatoid arthritis?
    Reinhard E Voll
    Department of Internal Medicine III, Friedrich Alexander University of Erlangen Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany
    Ann N Y Acad Sci 1051:799-810. 2005
    ....
  38. ncbi Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial
    Shumpei Yokota
    Department of Paediatrics, Yokohama City University School of Medicine, Yokohama, Japan
    Lancet 371:998-1006. 2008
    ..We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder...
  39. ncbi TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling
    Christoph Becker
    Laboratory of Immunology, I Medical Clinic, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
    Immunity 21:491-501. 2004
    ..Taken together, our data provide novel insights into TGF-beta signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on inhibition of TGF-beta-dependent IL-6 trans-signaling...
  40. ncbi Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin 6 receptor antibody MRA in rheumatoid arthritis. Phase I/II clinical study
    Norihiro Nishimoto
    Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Suita City, Japan
    J Rheumatol 30:1426-35. 2003
    ..To evaluate the safety and pharmacokinetics of multiple infusions of a humanized anti-interleukin-6 (IL-6) receptor antibody, MRA, in patients with rheumatoid arthritis (RA)...
  41. ncbi Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment
    M Romano
    Istituto Ricerche Farmacologiche Mario Negri, Milan, Italy
    Immunity 6:315-25. 1997
    ..Hence, in vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment...
  42. ncbi Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor
    K Yamasaki
    Division of Immunology, Osaka University, Japan
    Science 241:825-8. 1988
    ..The cytoplasmic domain of approximately 82 amino acids lacks a tyrosine/kinase domain, unlike other growth factor receptors...
  43. ncbi Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis
    Hideko Nakahara
    Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Osaka, Japan
    Arthritis Rheum 48:1521-9. 2003
    ..To investigate whether interleukin-6 (IL-6) is a regulator of vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA)...
  44. ncbi IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase
    M Murakami
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Science 260:1808-10. 1993
    ..Thus, a general first step in IL-6-related cytokine signaling may be the dimerization of signal-transducing molecules and activation of associated tyrosine kinases...
  45. pmc Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6
    T Tamura
    Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
    Proc Natl Acad Sci U S A 90:11924-8. 1993
    ..This may play an important physiological or pathological role in conditions associated with increased osteoclastic bone resorption...
  46. ncbi Interleukin-6 trans-signalling in chronic inflammation and cancer
    J Scheller
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Kiel, Germany
    Scand J Immunol 63:321-9. 2006
    ..The pathophysiologic mechanisms by which the IL-6/soluble IL-6R complex perpetuates the inflammatory state are discussed...
  47. ncbi Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells
    Harald Staiger
    Department of Endocrinology, Metabolism and Pathobiochemistry, Medical Clinic, Eberhard Karls University, Tubingen, Germany
    Diabetes 53:3209-16. 2004
    ..29, P < 0.05). We show here that the common plasma FFA palmitate induces high levels of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This points to a potential contribution of palmitate to vascular inflammation...
  48. ncbi IL-6 signal transduction and its physiological roles: the signal orchestration model
    D Kamimura
    Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
    Rev Physiol Biochem Pharmacol 149:1-38. 2003
    ....
  49. ncbi Signaling mechanisms through gp130: a model of the cytokine system
    T Hirano
    Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan
    Cytokine Growth Factor Rev 8:241-52. 1997
    ....
  50. ncbi Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial
    Norihiro Nishimoto
    Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Suita City, Osaka, Japan
    Arthritis Rheum 50:1761-9. 2004
    ..This study was undertaken to evaluate the safety and efficacy of a humanized anti-IL-6 receptor antibody, MRA, in patients with RA...
  51. ncbi Humanized antibody to human interleukin-6 receptor inhibits the development of collagen arthritis in cynomolgus monkeys
    M Mihara
    Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan
    Clin Immunol 98:319-26. 2001
    ..Our results demonstrate that IL-6 plays an important role in monkey CIA and that MRA may be an attractive agent for the treatment of rheumatoid arthritis...
  52. ncbi A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease
    Hiroaki Ito
    Department of Molecular Medicine, Graduate School of Medicine, Osaka University, Suita
    Gastroenterology 126:989-96; discussion 947. 2004
    ..We carried out a pilot placebo-controlled study to investigate the efficacy, pharmacokinetics, and safety of MRA, a humanized monoclonal antibody to IL-6 receptor, in patients with active Crohn's disease...
  53. ncbi Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism
    S Horiuchi
    Department of Microbiology, Faculty of Medicine, Tokyo Medical and Dental University, Japan
    Eur J Immunol 24:1945-8. 1994
    ..Our results indicate that active deletion of the TM domain by alternative splicing of mRNA represents one mechanism for release of sIL-6R into the culture supernatants of cells, or into serum or urine...
  54. ncbi Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130
    M Narazaki
    Division of Immunology, Osaka University, Japan
    Blood 82:1120-6. 1993
    ..Recombinant sgp130 showed inhibitory effect on the biologic function of such cytokines. This work implies physiologic roles of naturally produced serum sgp130 in modulating signals through gp130...
  55. ncbi IL-6 transsignaling: the in vivo consequences
    Simon A Jones
    Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, UK
    J Interferon Cytokine Res 25:241-53. 2005
    ..The mechanism by which the IL-6/sIL-6R complex regulates the inflammatory or neoplastic state is discussed...
  56. ncbi Interleukin-6 receptor gene variations, plasma interleukin-6 levels, and type 2 diabetes in U.S. Women
    Lu Qi
    Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA
    Diabetes 56:3075-81. 2007
    ..To examine the associations between common variations in the IL6R gene and circulating interleukin (IL)-6 levels and diabetes risk...
  57. ncbi Molecular screening and association analyses of the interleukin 6 receptor gene variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity
    Hua Wang
    Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Clin Endocrinol Metab 90:1123-9. 2005
    ..IL-6R is not likely to explain the linkage to diabetes in this region, but our work supports a minor role of variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA levels and possibly levels of soluble IL-6R...
  58. ncbi IL-6 signaling promotes tumor growth in colorectal cancer
    C Becker
    Lab of Immunology, I Medical Clinic, University of Mainz, Mainz, Germany
    Cell Cycle 4:217-20. 2005
    ..In summary, our data provide novel insights into the role of TGF-beta signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on an inhibition of TGF-beta-dependent IL-6 trans-signaling...
  59. ncbi Investigation of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130) in sera of cancer patients
    E Kovacs
    Society for Cancer Research, Arlesheim, Switzerland
    Biomed Pharmacother 55:391-6. 2001
    ..This is the first report to investigate sgp130 in cancer patients with different types of tumour...
  60. ncbi Tocilizumab: an interleukin-6 receptor inhibitor for the treatment of rheumatoid arthritis
    Susyn L Plushner
    Clinical Pharmacy Specialist in Rheumatology and Therapeutic Initiatives, 2045 Franklin St, Denver, CO 80205, USA
    Ann Pharmacother 42:1660-8. 2008
    ..To review the pharmacology, pharmacokinetics, clinical trial data, and safety profile of tocilizumab, a new biologic agent targeting the interleukin-6 cytokine receptor...
  61. pmc Interleukin-6 receptor gene, plasma C-reactive protein, and diabetes risk in women
    Lu Qi
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
    Diabetes 58:275-8. 2009
    ..Because IL6R variants were previously associated with IL-6 levels, we tested whether the associations with CRP were independent of IL-6 and the interactions between IL6R variants and CRP in relation to diabetes risk...
  62. pmc Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels
    David Reich
    Department of Genetics, Harvard Medical School, New Research Building, Boston, MA 02115, USA
    Am J Hum Genet 80:716-26. 2007
    ..0x10-12 for IL-6 SR, and P<2.0x10-9 for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant...
  63. ncbi Induction of neuronal and myelin-related gene expression by IL-6-receptor/IL-6: a study on embryonic dorsal root ganglia cells and isolated Schwann cells
    Pei Lin Zhang
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
    Exp Neurol 208:285-96. 2007
    ..On the contrary, we observed that IL6RIL6 inhibited the genes related to TGF-beta family as well as the production of smooth muscle actin...
  64. pmc Exacerbation of chronic active Epstein-Barr virus infection in a patient with rheumatoid arthritis receiving humanised anti-interleukin-6 receptor monoclonal antibody
    J Ogawa
    Ann Rheum Dis 65:1667-9. 2006
  65. ncbi sIL-6R: more than an agonist?
    Heike Knüpfer
    Institute of Clinical Pharmacology, University of Leipzig, Härtelstrasse 16 18, Leipzig, Germany
    Immunol Cell Biol 86:87-91. 2008
    ..Knowledge about additional properties of sIL-6R will enlarge the biologic understanding of this molecule and might give an explanation for the sometimes contrasting effects of the cytokine IL-6...
  66. ncbi The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases
    Karl Josef Kallen
    Biochemisches Institut, Christian Albrechts Universitat zu Kiel, Germany
    Biochim Biophys Acta 1592:323-43. 2002
    ..A specific treatment option for diseases influenced by the sIL-6R could be based on gp130-Fc, a soluble gp130 (sgp130) linked to the Fc-fragment of IgG1. gp130-Fc has shown efficacy in vivo in animal models of Crohn's disease...
  67. ncbi The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-alpha-induced apoptosis
    Yadav Wagley
    Department of Anatomy, College of Medicine, Chosun University, 375 Seosuk dong, Dong Gu, Gwangju, Republic of Korea
    Biochem Biophys Res Commun 354:985-91. 2007
    ..These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-alpha-resistant melanoma cells to TNF-alpha-induced apoptosis, may provide a new target for immunotherapy...
  68. ncbi Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130
    Mari A Nowell
    Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
    J Immunol 171:3202-9. 2003
    ..Specific blockade of soluble IL-6R signaling in wild-type mice using soluble gp130 ameliorated disease. Consequently, soluble IL-6R-mediated signaling represents a promising therapeutic target for the treatment of rheumatoid arthritis...
  69. ncbi Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis
    Shumpei Yokota
    Yokohama City University School of Medicine, Kanagawa, Japan
    Arthritis Rheum 52:818-25. 2005
    ....
  70. ncbi Novel role of IL-6/SIL-6R signaling in the expression of inducible nitric oxide synthase (iNOS) in murine B16, metastatic melanoma clone F10.9, cells
    Keon Wook Kang
    College of Pharmacy, Chosun University, Gwangju 501 759, Korea
    Free Radic Biol Med 42:215-27. 2007
    ..These results suggest that IL-6/sIL-6R/gp130 complex signaling has an unexpected positive effect on iNOS gene expression through JNK/p38 MAPK mediated-AP-1 activation in melanoma cells...
  71. ncbi Interleukin-6 directly influences proliferation and invasion potential of head and neck cancer cells
    Takeharu Kanazawa
    Department of Otolaryngology, Jichi Medical University, Omiya Medical Center, 857 1 Amanuma, Omiya Saitama City, Saitama, 330 8503, Japan
    Eur Arch Otorhinolaryngol 264:815-21. 2007
    ..These results suggest that IL-6 can directly influence cell proliferation and the invasion potential as the first step of tumor metastasis...
  72. ncbi Interleukin-6 trans-signaling in inflammatory bowel disease
    Keiichi Mitsuyama
    Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi machi 67, Kurume 830 0011, Japan
    Cytokine Growth Factor Rev 17:451-61. 2006
    ..These studies suggest that IL-6 trans-signaling may play a role in the development of IBD; they therefore imply the possibility of a selective therapeutic strategy to target this signaling...
  73. pmc Interleukin-6/soluble interleukin-6 receptor signaling attenuates proliferation and invasion, and induces morphological changes of a newly established pleomorphic malignant fibrous histiocytoma cell line
    Hirofumi Nakanishi
    Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1 3 3 Nakamichi, Higashinari ku, Osaka 537 8511, Japan
    Am J Pathol 165:471-80. 2004
    ....
  74. pmc Interleukin-6: discovery of a pleiotropic cytokine
    Tadamitsu Kishimoto
    Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
    Arthritis Res Ther 8:S2. 2006
    ..When taking into account all the accumulated basic research on the various aspects of this molecule, it appeared that blocking the activity of IL-6 was a feasible, new therapeutic approach for chronic inflammatory diseases...
  75. ncbi The designer cytokine hyper-IL-6 mediates growth inhibition and GM-CSF-dependent rejection of B16 melanoma cells
    S Ozbek
    Department of Medicine, Section of Pathophysiology, University of Mainz, Obere Zahlbacher Strasse 63, D-55101 Mainz, Germany
    Oncogene 20:972-9. 2001
    ..These results demonstrate that the anti-tumor effect of cytokines like IL-6 which are secreted by transfected melanoma cells at least in part depends on GM-CSF activity...
  76. ncbi Serum interleukin-6, soluble interleukin-6 receptor and soluble gp130 exhibit different patterns of age- and menopause-related changes
    N Giuliani
    Dipartimento di Medicina Interna e Scienze Biomediche, , Via Gramsci 14, 43100, Parma, Italy
    Exp Gerontol 36:547-57. 2001
    ....
  77. ncbi IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage
    C R Flannery
    Connective Tissue Biology Research Group, Cardiff School of Biosciences, Cardiff University, Museum Avenue, CF10 3US, Cardiff, UK
    Matrix Biol 19:549-53. 2000
    ..This catabolism was associated with aggrecanase (but not MMP) activity, with correlative mRNA expression for aggrecanase-2...
  78. ncbi Effects of IL-6 and its soluble receptor on proteoglycan synthesis and NO release by human articular chondrocytes: comparison with IL-1. Modulation by dexamethasone
    P A Guerne
    Division of Rheumatology, Hopital Cantonal Universitaire, Geneva, Switzerland
    Matrix Biol 18:253-60. 1999
    ..In conclusion, sIL-6Ralpha potentiates the inhibitory effect of IL-6 on PG synthesis by articular chondrocytes, but the overall effect of IL-6 + IL-6sR is moderate compared to the effects of IL-1...
  79. ncbi IL-6 as an intracrine growth factor for renal carcinoma cell lines
    Laurent Alberti
    Equipe Cytokine et Cancer, Unité Inserm 590, Lyon, France
    Int J Cancer 111:653-61. 2004
    ..IL-6 ASON inhibited the proliferation of the 8 RCC cell lines tested additively with IL-4 or IL-13. IL-6 is an intracrine growth factor in renal cell carcinoma cell lines...
  80. ncbi Increased levels of plasma interleukin-6 soluble receptor in patients with essential thrombocythemia
    Rosana Marta
    Sección Hematología Investigación, Instituto de Investigaciones Medicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina
    Haematologica 89:657-63. 2004
    ..We also evaluated IL-6R on leukocyte membrane and IL-6R/IL-6sR mRNA expression in mononuclear cells...
  81. ncbi Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis
    Shumpei Yokota
    Department of Pediatrics, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan
    Clin Rev Allergy Immunol 28:231-8. 2005
    ..A confirmation of the role of tocilizumab in the treatment of sJIA will be provided by the results of the ongoing phase III study in Japan...
  82. ncbi The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation: an experimental model involving thrombin
    V Marin
    , , and Immunotech, a Beckman Coulter Company, Marseille, France
    J Immunol 167:3435-42. 2001
    ..sIL-6Ralpha may then complex with IL-6 and increase the amount of MCP-1 produced by thrombin-activated endothelium, favoring monocyte infiltration, and the transformation of acute into chronic inflammation...
  83. pmc Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis
    T Sugita
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    J Exp Med 171:2001-9. 1990
    ..Since IL-6 functions as a potent growth factor for murine plasmacytomas, over-expression of abnormal IL-6-R may function as a positive selection element for the development of certain plasmacytomas...
  84. ncbi IL-6/sIL-6R trans-signalling, but not TNF-alpha induced angiogenesis in a HUVEC and synovial cell co-culture system
    Misato Hashizume
    Product Research Department, Chugai Pharmaceutical Co, Ltd, Gotemba, Shizuoka 412 8513, Japan
    Rheumatol Int 29:1449-54. 2009
    ..In conclusion, IL-6/sIL-6R complex showed angiogenic activity via the production of VEGF from RA-FLS, but TNF-alpha was anti-angiogenic in our experimental system...
  85. ncbi CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130
    N Y Ip
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591
    Cell 69:1121-32. 1992
    ..Thus, the receptor system for CNTF is surprisingly unlike those used by the nerve growth factor family of neurotrophic factors, but is instead related to those used by a subclass of hematopoietic cytokines...
  86. pmc Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs
    Stephan W Lindemann
    Program in Human Molecular Biology and Genetics, University of Utah, 15 North, 20230 East, Building 533, Room 4220, Salt Lake City, UT 84112, USA
    Proc Natl Acad Sci U S A 101:7076-81. 2004
    ..Signal-dependent translation in activated neutrophils may be a critical mechanism for alteration of the inflammatory milieu and a therapeutic target...
  87. ncbi Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease
    Norihiro Nishimoto
    Laboratory of Immune Regulation, Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan
    Blood 112:3959-64. 2008
    ..We also concluded that the increased level of free IL-6 during tocilizumab treatment closely reflects the actual endogenous IL-6 production and true disease activity...
  88. ncbi [Interleukin-6 in pathogenesis of rheumatoid arthritis]
    Masahiko Mihara
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co Ltd
    Nihon Rinsho 63:158-62. 2005
  89. ncbi Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons
    O Obreja
    Institut fur Physiologie und Experimentelle Pathophysiologie, Friedrich Alexander Universitat, Erlangen Nurnberg, Germany
    Brain 128:1634-41. 2005
    ..Together, the results suggest that IL-6-sIL-6R acts directly on sensory neurons. It increases their susceptibility to noxious heat via the gp130/Jak/PKCdelta signalling pathway...
  90. ncbi Central role of IL-6 receptor signal-transducing chain gp130 in activation of L-selectin adhesion by fever-range thermal stress
    Qing Chen
    Department of Immunology, Roswell Park Cancer Institute, Carlton and Elm Streets, Buffalo, NY 14263, USA
    Immunity 20:59-70. 2004
    ..These results highlight a role for gp130-linked IL-6/sIL-6Ralpha transsignaling in amplifying lymphocyte trafficking during febrile inflammatory responses...
  91. ncbi TNF-alpha induces tyrosine phosphorylation and recruitment of the Src homology protein-tyrosine phosphatase 2 to the gp130 signal-transducing subunit of the IL-6 receptor complex
    Johannes G Bode
    Klinik fur Gastroenterologie, Hepatologie und Infektiologie, Medizinische Klinik der Heinrich Heine Universität, Dusseldorf, Germany
    J Immunol 171:257-66. 2003
    ..Furthermore, activation of p38 mitogen-activated protein kinase is shown to be essential for the inhibitory effect of TNF-alpha on IL-6 signaling and TNF-alpha-dependent recruitment of SHP2 to gp130...
  92. ncbi Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor
    Georgios Skiniotis
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Struct Mol Biol 12:545-51. 2005
    ..Variation in the receptor bend angles suggests a possible conformational transition from open to closed states upon ligand binding; this transition is probably representative of the other tall cytokine receptors...
  93. ncbi Bow to your partner for signaling
    Heike M Hermanns
    Nat Struct Mol Biol 12:476-8. 2005
  94. ncbi Norepinephrine-induced interleukin-6 increase in rat hearts: differential signal transduction in myocytes and non-myocytes
    W Briest
    Carl Ludwig Institute of Physiology, University of Leipzig, Liebigstrasse 27, 04103 Leipzig, Germany
    Pflugers Arch 446:437-46. 2003
    ..In contrast, the IL6R protein and the downstream regulator STAT3 were increased only in MCs after 24 h of NE infusion. The mRNA of C/EBP-delta, which is regulated by STAT3, was elevated only in myocytes...
  95. ncbi In vivo modulation of soluble "antagonistic" IL-6 receptor synthesis and release in ESRD
    Bruno Memoli
    Department of Nephrology, University Federico II of Naples, Via Tasso 91 B, Napoli 80127, Italy
    J Am Soc Nephrol 16:1099-107. 2005
    ..This release is seemingly due to a shedding of membrane-bound gp130 receptor. The increased sgp130 release may partially counteract the inflammatory effects caused by IL-6...
  96. ncbi Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation
    Cecile Ancey
    Laboratoire des Biomembranes et Signalisation Cellulaire, UMR CNRS 6558, Universite de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France
    Cardiovasc Res 59:78-85. 2003
    ..The present study aims to analyse the capacity of human atrial cardiac cells (i.e., cardiomyocytes and fibroblasts) to display the gp130 receptor subunit, and to evaluate its functionality...
  97. ncbi Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate
    Mar Royuela
    Department of Cell Biology and Genetics, University of Alcala, Madrid, Spain
    J Pathol 202:41-9. 2004
    ..The role of OSM mainly in high Gleason grade carcinomas makes OSM a putative target for prostate cancer therapy...
  98. ncbi Enhancement of oligodendrocyte differentiation from murine embryonic stem cells by an activator of gp130 signaling
    Peilin Zhang
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Stem Cells 22:344-54. 2004
    ..We conclude that this cytokine can significantly enhance the derivation of oligodendrocytes from ES cells...
  99. ncbi A combination of interleukin-6 and its soluble receptor impairs sperm motility: implications in infertility associated with endometriosis
    Souichi Yoshida
    Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago 683 8504, Japan
    Hum Reprod 19:1821-5. 2004
    ..This study was undertaken to assess the effects of IL-6 and soluble IL-6 receptor (sIL-6R) on in vitro sperm motility...
  100. ncbi Molecular mechanisms for viral mimicry of a human cytokine: activation of gp130 by HHV-8 interleukin-6
    Martin J Boulanger
    Department of Microbiology and Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94305 5124, USA
    J Mol Biol 335:641-54. 2004
    ..Viral IL-6 appears to utilize an elegant combination of both convergent, and unexpectedly divergent, molecular strategies to oligomerize gp130 and activate similar downstream signaling cascades as its human counterpart...
  101. pmc The role of the inhibitors of interleukin-6 signal transduction SHP2 and SOCS3 for desensitization of interleukin-6 signalling
    Patrick Fischer
    Department of Biochemistry, Faculty of Medicine, RWTH Aachen, Pauwelsstrasse 30, D 52074 Aachen, Germany
    Biochem J 378:449-60. 2004
    ..Furthermore, cells lacking SOCS3 show constitutive STAT3 activation which is not affected by pre-stimulation with IL-6. All these observations suggest that desensitization and inhibition of signalling are mechanistically distinct...

Research Grants62

  1. Reperfusion and Neurovascular Injury in Stroke
    Pak H Chan; Fiscal Year: 2013
    ....
  2. 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. ..
  3. Central Mechanisms of Orofacial Pain
    Jianren Mao; Fiscal Year: 2012
    ..The outcome of this study could lead to the development of new therapeutic tools to treat often intractable and debilitating clinical orofacial pain. ..
  4. Characterizing Inflammation And Downstream Effects During Chronic Viral Infection
    Elina I Zuniga; Fiscal Year: 2012
    ..Furthermore, since LCMV is considered a prototypic arenavirus the proposed studies will increase our understanding of the pathogenesis of human arenaviruses, which cause fatal hemorrhagic fevers. ..
  5. The Role of IL-6 Receptor in Irritant Dermatitis
    RANDLE MICHAEL GALLUCCI; Fiscal Year: 2013
    ..This research may also provide the rational for IL-6 based therapies that may find use in the prophylaxis or treatment of occupational dermatitis. ..
  6. ADAM17 in pancreatic cancer and pancreatitis
    Howard C Crawford; Fiscal Year: 2013
    ....
  7. The role of IL-6 in jet fuel irritant dermatitis
    RANDLE MICHAEL GALLUCCI; Fiscal Year: 2010
    ....
  8. Effects of IL-6 blockade in treated HIV infection
    Benigno Rodriguez; Fiscal Year: 2013
    ..We will examine the effects of IL-6 receptor blockade on the peripheral blood leukocyte transcriptome and plasma metabolome and relate these to functional assays of immune pathogenesis and cardiovascular risk. ..
  9. Genotypic Interactions in Brain Cancer Heterogeneity
    Frank B Furnari; Fiscal Year: 2013
    ....
  10. Pain and Well-being in Older Women: The Roles of Activity and Motivation
    Suzanne C Segerstrom; Fiscal Year: 2013
    ..The study will advance understanding of how a common, age-relevant experience - physical pain - affects EWB and physical health. ..
  11. Development of a Novel RA/Atherosclerosis Mouse Model
    HARRIS R PERLMAN; Fiscal Year: 2013
    ..We predict that amelioration of both diseases will correlate with a reduction in tissue macrophages. ..
  12. Translational Regulation of Gene Expression in Neonatal PMNs
    Christian Con Yost; Fiscal Year: 2010
    ..Results of these experiments will provide new and important mechanistic insight into the pathogenesis of NEC, and may lead to improvements in the prevention and treatment of this common and often devastating disease of prematurity. ..
  13. Regulation of hemopoietic stem cell expansion by calciotrophic hormones
    Roberto Pacifici; Fiscal Year: 2013
    ..New data about the role of T lymphocytes in the mechanism by which estrogen and PTH regulate HSCs will increase the scope and the depth of osteoimmunology, a novel field of multidisciplinary research. ..
  14. Blocking of IL-6 function to prevent Pg mediated Th17 response
    JAN S POTEMPA; Fiscal Year: 2013
    ..Positive findings will establish the regulation of human Th17 cells by P. gingivalis adhesins and gingipains. Results of the present investigation will be useful in design of novel therapeutic targets. ..
  15. NMR approaches to STAT3 structural characterization and inhibitor design
    ANDREW TAYANJANA NAMANJA; Fiscal Year: 2013
    ..abstract_text> ..
  16. Small-Molecule Antibody Recruiting Therapeutics for Treating Human Disease
    David Spiegel; Fiscal Year: 2009
    ..If successful, the proposed method would represent a novel therapeutic approach to a variety of human diseases. ..
  17. Cytokine control of Red Blood Cell Alloimmunization
    CHANCE MARION JOHN LUCKEY; Fiscal Year: 2013
    ..In the fullness of time, we anticipate that identification of the molecular circuitry driving RBC antibody production will provide therapeutic and diagnostic targets for further clinical development. ..
  18. INHIBITION OF IL-6 AND STAT3 IN RHEUMATOID ARTHRITIS
    Lionel Ivashkiv; Fiscal Year: 1999
    ..3) Characterize the functional consequences of ERK-mediated inhibition of IL-6 signal transduction using the M1 myeloid cell differentiation system. ..
  19. Transplantation: Graft Cell Promotion of Rejection
    David Perkins; Fiscal Year: 2004
    ..Aim 2 will identify cells in the peripheral lymphoid tissue with IL-6 dependent activation. And, Aim 3 will determine the mechanisms of IL-6 dependent activation of alloimmune responses by modulation of regulatory T cells. ..
  20. Normal and UV-Induced cutaneous antigen presenting cells
    Kevin Cooper; Fiscal Year: 2007
    ..Aim III translates these findings in vivo to confirm their role in integrated immune response regulation, leading to novel immunotherapeutic strategies with clinical impact. ..
  21. Inflammatory factors, genes and stress induced pressure natriuresis in youth
    Haidong Zhu; Fiscal Year: 2007
    ..Understanding the connections between stress, inflammation, and genes will provide a fresh approach into evaluating risk factors for high blood pressure. [unreadable] [unreadable] [unreadable]..
  22. Health Effects of Air Pollution in an Elderly Population
    Jeffrey Sullivan; Fiscal Year: 2006
    ..Elucidating molecular mechanisms of susceptibility to air pollution induced morbidity will aid in designing public health policy to prevent morbidity and mortality from air pollution. ..
  23. Integrin CD11b and its role in immune suppression
    Li Zhang; Fiscal Year: 2010
    ....
  24. IN VIVO REGULATION OF IL6 AND IL6R GENE EXPRESSION
    CHARLES O BRIEN; Fiscal Year: 2002
    ..Finally, cis-acting regulatory elements in the IL-6 promoter that are the targets for estrogen and PTH actions in vivo will be identified. ..
  25. ERBB KINASE ACTIVATION AND TRANSFORMATION
    Hsing Jien Kung; Fiscal Year: 2004
    ..The present proposal is based on the above three novel findings and intends to study: 1) the mechanisms involved in receptor cross talk between erbB2 and IL6 receptor and 2) the NED signal pathways mediated by erbB2 and Etk. ..
  26. IL-6 & SIL-6R GROWTH INHIBITION OF BREAST CARCINOMA
    NITA MAIHLE; Fiscal Year: 1999
    ....
  27. Cell-targeting peptide nucleic acids for hormone-refractory prostate cancer
    Beverly Barton; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  28. role of adipokines in colon epithelial cell homeostasis
    JENIFER FENTON; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  29. Skeletal muscle contractile dysfunction in heart failure
    MICHAEL TOTH; Fiscal Year: 2009
    ..Our findings will also provide information regarding the utility of resistance exercise training to improve single muscle fiber function, as well as whole muscle performance and whole body physical function in heart failure patients. ..
  30. Role of IL-6 and estrogen in PTH-induced bone resorption
    Urszula Masiukiewicz; Fiscal Year: 2003
    ..3. Examine the molecular mechanism underlying PTH-induced increases in IL-6 production by bone cells and the modulating effect of estrogen on this process. ..
  31. Effects of ovarian suppression on substrate metabolism
    MICHAEL TOTH; Fiscal Year: 2007
    ..Our findings will have direct relevance to understanding the fundamental role of ovarian hormone deficiency in the physiologic and metabolic changes that occur with menopause. ..
  32. SKELETAL MUSCLE PROTEIN METABOLISM IN HEART FAILURE
    MICHAEL TOTH; Fiscal Year: 2001
    ..These experiments will provide new information regarding the pathophysiological mechanisms responsible for the loss of skeletal muscle protein quality and quantity in heart failure patients. ..
  33. SKELETAL MUSCLE PROTEIN METABOLISM IN HEART FAILURE
    MICHAEL TOTH; Fiscal Year: 2003
    ..These experiments will provide new information regarding the pathophysiological mechanisms responsible for the loss of skeletal muscle mass and strength in heart failure patients. ..
  34. THROMBOTIC, INFLAMMATORY & GENE MARKERS OF CVD IN WOMEN
    Paul Ridker; Fiscal Year: 2002
    ....
  35. SECONDARY PREVENTION TRIAL OF VENOUS THROMBOSIS
    Paul Ridker; Fiscal Year: 2002
    ....
  36. IL-6 AND ESTROGEN AND PTH INDUCED BONE RESORPTION
    Urszula Masiukiewicz; Fiscal Year: 2002
    ..3) We will study the molecular mechanism of the PTH-induced increase in IL-6 production by bone cells and the modulating effect of estrogen on this process. ..
  37. Phase II Trial of Thalidomide in Primary Amyloidosis
    Angela Dispenzieri; Fiscal Year: 2002
    ..The ultimate goal of the proposed studies is to improve the prognosis of patient with this fatal disease. ..
  38. Oncostatin M and Leukemia Inhibitory Factor Biology
    Heinz Baumann; Fiscal Year: 2004
    ..Understanding the cell type-specific regulation of IL-6-type cytokine receptor activities will assist in designing treatments that will manipulate beneficial IL-6 cytokine effects during inflammation and tissue repair. ..
  39. CYTOKINE REGULATION OF MATURE MYELIN-SPECIFIC T CELLS
    Benjamin Segal; Fiscal Year: 2004
    ..These studies may have therapeutic relevance to MS as well as provide insights into the pathways by which IL-12 regulates differentiated effector T cells. ..
  40. CELL ADHESION IN TISSUE MORPHOGENESIS
    William Carter; Fiscal Year: 2001
    ..these results will define the molecular mechanism through which cell adhesion regulates gene expression and wound repair in epithelium. ..
  41. MOLECULAR AND BIOLOGICAL FUNCTION OF CD40 IN MYELOMA
    Diane Jelinek; Fiscal Year: 2002
    ....
  42. CELLULAR PHYSIOLOGY OF STAT3
    PRAVIN SEHGAL; Fiscal Year: 2002
    ..Establishing the basic subunit structure of the cytosolic 200-400 kDa and 1-2 MDa STAT3-containing complexes in IL-6-free and IL-6-treated cells is a sine qua non for further progress in this field. ..
  43. DEVELOPMENT OF A NOVEL BIOARTIFICIAL LIVER
    Jacek Rozga; Fiscal Year: 2002
    ..S. lone to keep liver failure patients alive until an organ becomes available for transplantation or the native liver recovers from injury ($1.5-billion market). ..
  44. MITOGENIC SIGNALING BY ENDOTHELIN PEPTIDES
    Michael Simonson; Fiscal Year: 2002
    ..Finally, whether rho is in the Src pathway or not, will be examined by cotransfection with constitutively active v-Src/dominant negative RhoA and vice versa and evaluation of c-fos induction/ DNA synthesis. ..
  45. AGING, GENE EXPRESSION AND OXIDATIVE STRESS
    Evan Keller; Fiscal Year: 2002
    ....
  46. Lung epithelium-derived IL-6 in CD4+ T cell immune resp*
    Mercedes Rincon; Fiscal Year: 2004
    ..abstract_text> ..
  47. VEGF and bone remodeling in skeletal metastases
    Evan Keller; Fiscal Year: 2005
    ..In this aim, we will test which VEGF isoform contributes to CaP cells' osteoblastic activity. We will also evaluate if VEGF induces this activity through MAPK. ..
  48. Cytokine Polymorphisms and Hodgkin Lymphoma Risk
    Wendy Cozen; Fiscal Year: 2006
    ..This study is important since it may will lead to identification of causal genetic factors which may offer alternative therapeutic strategies or prevention. ..
  49. Intimate Partner Violence and Inflammatory Processes
    Tamara Newton; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  50. Associating genetic variation to resistance to severe malaria in East Africa
    David Reich; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  51. Differential Gene Expression in the Cochlear Nucleus
    David Friedland; Fiscal Year: 2008
    ..These data will also provide a powerful template upon which to test and design novel treatments for improving hearing, discrimination and tinnitus in a significant portion of the population. ..
  52. Identification of an IL-6 induced keratinocyte motogen
    RANDLE GALLUCCI; Fiscal Year: 2008
    ..The results of these experiments will hopefully lead to the eventual development of a useful treatment for chronic wounds. ..
  53. Gene-Environment Interactions in Obesity and Diabetes
    Tracy Nelson; Fiscal Year: 2007
    ..Environment: Dr. Nelson will have an outstanding environment in which to carry out the proposed study, as well as, the necessary resources and support to successfully complete her training. ..
  54. Monocyte / Macrophage TLR4 Expression and Signaling: A Link between Obesity and C
    Brian McFarlin; Fiscal Year: 2008
    ..The primary purpose of this investigation is to determine if obesity status alters TLR4 signaling and/or inflammatory cytokine production in blood monocyte and adipose tissue macrophage. [unreadable] [unreadable] [unreadable]..
  55. Genetic Studies of Substance Abuse in Iowa Adoptees
    Robert Philibert; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  56. Advanced Training in Clinical Investigation
    Bruce Cronstein; Fiscal Year: 2008
    ..We strongly believe that creation of this new program to prepare the next generation of clinician-investigators to bring the remarkable advances made at the bench to the patient. ..
  57. MECHANISMS OF AUTOREACTIVITY IN SLE
    Robert Eisenberg; Fiscal Year: 2009
    ..Such insights should be readily translatable to human autoimmune diseases. ..
  58. PLACENTAL FUNCTION IN PREECLAMPSIA
    Yuping Wang; Fiscal Year: 2009
    ..Results obtained from the proposed work should enhance our knowledge and establish a direct link of placental TC activity and EC dysfunction in PE. ..
  59. Gender differences in liver IL-6R expression
    RANDLE GALLUCCI; Fiscal Year: 2007
    ..By exposing ethanol- consuming rats to IL-6R agonists, it should be possible to correlate damage with receptor activation. [unreadable] [unreadable] [unreadable]..
  60. Raft/Caveolar Mechanisms in Pulmonary Hypertension
    PRAVIN SEHGAL; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  61. Pro & Anti-Inflammatory Cytokines in Colorectal Cancer
    GLORIA YF HO; Fiscal Year: 2010
    ..These high-risk individuals may benefit from prophylactic NSAIDS for prevention of colorectal cancer. ..
  62. PHARMACOLOGIC PROMOTION OF WOUND HEALING
    Bruce Cronstein; Fiscal Year: 2007
    ..These studies should provide new insights into the mechanism by which adenosine A2A receptor agonists, a novel therapy undergoing clinical trials for wound healing of diabetic foot ulcers, promote wound healing. ..