interleukin 12

Summary

Summary: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity.

Top Publications

  1. ncbi Interleukin-12 and the regulation of innate resistance and adaptive immunity
    Giorgio Trinchieri
    Laboratory for Immunological Research, Schering Plough Research Institute, 27 chemin des Peupliers, B P 11, 69571 Dardilly, France
    Nat Rev Immunol 3:133-46. 2003
  2. ncbi The immunology of susceptibility and resistance to Leishmania major in mice
    David Sacks
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 2:845-58. 2002
  3. pmc IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
    Claire L Langrish
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    J Exp Med 201:233-40. 2005
  4. ncbi Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
    Daniel J Cua
    Department of Immunology, DNAX Research Inc, Palo Alto, California 94304 1104, USA
    Nature 421:744-8. 2003
  5. ncbi Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages
    C S Hsieh
    Department of Pathology, Washington University School of Medicine, St Louis, MO 63110
    Science 260:547-9. 1993
  6. ncbi In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha
    R T Gazzinelli
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    J Immunol 157:798-805. 1996
  7. ncbi T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells
    Maryam Afkarian
    Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 S Euclid Ave, St Louis, MO 63110, USA
    Nat Immunol 3:549-57. 2002
  8. ncbi Interleukin-12 in anti-tumor immunity and immunotherapy
    Mario P Colombo
    Department of Experimental Oncology, Immunotherapy and Gene Therapy Unit, Istituto Nazionale Tumori, Via G Venezian 1, Milan 20133, Italy
    Cytokine Growth Factor Rev 13:155-68. 2002
  9. pmc Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells
    S J Szabo
    Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Exp Med 185:817-24. 1997
  10. ncbi New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions
    Christopher A Hunter
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA
    Nat Rev Immunol 5:521-31. 2005

Detail Information

Publications354 found, 100 shown here

  1. ncbi Interleukin-12 and the regulation of innate resistance and adaptive immunity
    Giorgio Trinchieri
    Laboratory for Immunological Research, Schering Plough Research Institute, 27 chemin des Peupliers, B P 11, 69571 Dardilly, France
    Nat Rev Immunol 3:133-46. 2003
    ....
  2. ncbi The immunology of susceptibility and resistance to Leishmania major in mice
    David Sacks
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Immunol 2:845-58. 2002
    ..major-resistant mice have revealed complexities in the mechanisms responsible for acquired immunity, which necessitate the redesign of vaccines against Leishmania and other pathogens that require sustained cell-mediated immune responses...
  3. pmc IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
    Claire L Langrish
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    J Exp Med 201:233-40. 2005
    ..Using passive transfer studies, we confirm that these IL-23-dependent CD4(+) T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity...
  4. ncbi Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
    Daniel J Cua
    Department of Immunology, DNAX Research Inc, Palo Alto, California 94304 1104, USA
    Nature 421:744-8. 2003
    ..In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages...
  5. ncbi Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages
    C S Hsieh
    Department of Pathology, Washington University School of Medicine, St Louis, MO 63110
    Science 260:547-9. 1993
    ..Therefore, this regulatory pathway may have evolved to enable innate immune cells, through interactions with microbial pathogens, to direct development of specific immunity toward the appropriate TH phenotype...
  6. ncbi In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha
    R T Gazzinelli
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    J Immunol 157:798-805. 1996
    ..Together the data suggest that endogenous IL-10 synthesis plays an important role in vivo in down-regulating monokine and IFN-gamma responses to acute intracellular infection, thereby preventing host immunopathology...
  7. ncbi T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells
    Maryam Afkarian
    Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 S Euclid Ave, St Louis, MO 63110, USA
    Nat Immunol 3:549-57. 2002
    ..Thus, T-bet is induced by IFN-gamma and STAT1 signaling during T cell activation. In addition, T-bet mediates STAT1-dependent processes of T(H)1 development, including the induction of IL-12Rbeta2...
  8. ncbi Interleukin-12 in anti-tumor immunity and immunotherapy
    Mario P Colombo
    Department of Experimental Oncology, Immunotherapy and Gene Therapy Unit, Istituto Nazionale Tumori, Via G Venezian 1, Milan 20133, Italy
    Cytokine Growth Factor Rev 13:155-68. 2002
    ..However, excessive clinical toxicity and modest clinical response observed in the clinical trials point to the necessity to plan protocols that minimize toxicity without affecting the anti-tumor effect of IL-12...
  9. pmc Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells
    S J Szabo
    Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Exp Med 185:817-24. 1997
    ..Thus, IFN-gamma may prevent early Th cells from premature commitment to the Th2 pathway. Controlling the expression of the IL-12R beta 2 subunit could be an important therapeutic target for the redirection of ongoing Th cell responses...
  10. ncbi New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions
    Christopher A Hunter
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA
    Nat Rev Immunol 5:521-31. 2005
    ..By contrast, IL-27 has a role in limiting the intensity and duration of adaptive immune responses...
  11. ncbi The biology of IL-12: coordinating innate and adaptive immune responses
    Wendy T Watford
    Molecular Immunology and Inflammation Branch, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA
    Cytokine Growth Factor Rev 14:361-8. 2003
    ..IL-12 and the recently identified cytokines, IL-23 and IL-27, define a family of related cytokines that induce IFN-gamma production and promote T cell expansion and proliferation...
  12. ncbi Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12
    B Oppmann
    DNAX Research Institute, Palo Alto, CA 94304, USA
    Immunity 13:715-25. 2000
    ..Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells...
  13. ncbi IL-12 and IL-23: master regulators of innate and adaptive immunity
    Claire L Langrish
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    Immunol Rev 202:96-105. 2004
    ..These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression...
  14. pmc Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells
    Giorgio Napolitani
    Institute for Research in Biomedicine, Oncology Institute of Southern Switzerland, CH 6500, Bellinzona, Switzerland
    Nat Immunol 6:769-76. 2005
    ..These results identify a 'combinatorial code' by which DCs discriminate pathogens and suggest new strategies for promoting T helper type 1 responses...
  15. ncbi Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells
    W E Thierfelder
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 382:171-4. 1996
    ..However, all IL-12 functions tested were disrupted, including the induction of IFN-gamma, mitogenesis, enhancement of natural killer cytolytic function and Th1 differentiation...
  16. ncbi IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available
    Shabaana A Khader
    Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983, USA
    J Immunol 175:788-95. 2005
    ....
  17. ncbi Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice
    M H Kaplan
    Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Nature 382:174-7. 1996
    ..These results demonstrate that Stat4 is essential for mediating responses to IL-12 in lymphocytes, and regulating the differentiation of both Th1 and Th2 cells...
  18. pmc Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice
    K Boggio
    Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy
    J Exp Med 188:589-96. 1998
    ....
  19. pmc Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
    Michael Martin
    Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
    Nat Immunol 6:777-84. 2005
    ..These findings demonstrate a regulatory function for GSK3 in modulating the inflammatory response...
  20. ncbi Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency
    F Altare
    INSERM U429, Hopital Necker Enfants Malades, Paris 75015, France
    Science 280:1432-5. 1998
    ..Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion...
  21. pmc Differential tumor surveillance by natural killer (NK) and NKT cells
    M J Smyth
    Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia
    J Exp Med 191:661-8. 2000
    ..This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide...
  22. ncbi Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets
    H Hochrein
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
    J Immunol 166:5448-55. 2001
    ..In contrast, the CD4(-)8(-) DC produced much more IFN-gamma than the CD4(-)8(+) or the CD4(+)8(-) DC under all conditions tested...
  23. ncbi IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses
    J Magram
    Department of Biotechnology, Roche Institute of Molecular Biology, Nutley, New Jersey 07110, USA
    Immunity 4:471-81. 1996
    ..However, other phenomena associated with Th1 responses and cell-mediated immunity, i.e., IL-2 secretion and CTL generation, were not compromised in the absence of IL-12...
  24. ncbi IL-4 instructs TH1 responses and resistance to Leishmania major in susceptible BALB/c mice
    T Biedermann
    Department of Dermatology and Allergology, Ludwig Maximilians University Munich, Frauenlobstr 9 11, 80337 Munich, Germany
    Nat Immunol 2:1054-60. 2001
    Immunity to infection with intracellular pathogens is regulated by interleukin 12 (IL-12), which mediates protective T helper type 1 (TH1) responses, or IL-4, which induces TH2 cells and susceptibility...
  25. ncbi CCR5 provides a signal for microbial induced production of IL-12 by CD8 alpha+ dendritic cells
    J Aliberti
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Nat Immunol 1:83-7. 2000
    The activation of dendritic cells (DC) to produce interleukin 12 (IL-12) is thought to be a key step in the initiation of cell-mediated immunity to intracellular pathogens...
  26. ncbi Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection
    Khuong B Nguyen
    Deparment of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
    J Immunol 169:4279-87. 2002
    ....
  27. ncbi Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist
    S Gillessen
    Department of Inflammation Autoimmune Diseases, Hoffmann La Roche Inc, Nutley, NJ 07110
    Eur J Immunol 25:200-6. 1995
    ..Further studies are required to determine whether or not (p40)2 is produced by normal lymphoid cells and is a physiologic regulator of IL-12 activity...
  28. pmc Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes
    C M Bacon
    Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 92:7307-11. 1995
    b>Interleukin 12 (IL-12) is an important immunoregulatory cytokine whose receptor is a member of the hematopoietin receptor superfamily...
  29. ncbi Role of T-bet in commitment of TH1 cells before IL-12-dependent selection
    A C Mullen
    Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Science 292:1907-10. 2001
    ..We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 effector fate by targeting chromatin remodeling to individual interferon-gamma (..
  30. ncbi CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine
    Julie M Curtsinger
    Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA
    J Immunol 171:5165-71. 2003
    ....
  31. ncbi Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features
    Orchidée Filipe-Santos
    Laboratory of Human Genetics of Infectious Diseases, University of Paris René Descartes INSERM U 550, Necker Medical School, 75015 Paris, France, EU
    Semin Immunol 18:347-61. 2006
    ..We review here the molecular, cellular, and clinical features of patients with inborn errors of the IL-12/23-IFN-gamma circuit...
  32. ncbi Functional interactions between dendritic cells and NK cells during viral infection
    Daniel M Andrews
    Department of Microbiology, School of Biomedical and Chemical Sciences, The University of Western Australia, Nedlands, Perth, Australia
    Nat Immunol 4:175-81. 2003
    ..This study provides evidence for a functional interrelationship between DCs and NK cells during viral infection and defines some of the critical cytokines...
  33. ncbi Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions
    Hedi Harizi
    Laboratoire d Immunologie, Unité Mixte de Recherche Centre National de la Recherche Scientifique, Universite Victor Segalen, Bordeaux 2, 33076 Bordeaux, France
    J Immunol 168:2255-63. 2002
    ..We conclude that COX-2-mediated PGE(2) up-regulates IL-10, which down-regulates IL-12 production and the APC function of BM-DC...
  34. ncbi A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R
    Christi Parham
    Department of Immunology, DNAX Research, Palo Alto, CA 94304, USA
    J Immunol 168:5699-708. 2002
    ..The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2...
  35. ncbi TLR11 activation of dendritic cells by a protozoan profilin-like protein
    Felix Yarovinsky
    Immunobiology Section, Laboratory of Parasitic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
    Science 308:1626-9. 2005
    ..Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens...
  36. ncbi Natural killer cells in antiviral defense: function and regulation by innate cytokines
    C A Biron
    Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA
    Annu Rev Immunol 17:189-220. 1999
    ..Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms...
  37. ncbi Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells
    Julio Aliberti
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Immunol 4:485-90. 2003
    ..The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts...
  38. ncbi The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23-->IL-17 axis
    Amir F Sheibanie
    Department of Physiology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USA
    J Immunol 178:8138-47. 2007
    ..These studies suggest that high levels of PGE(2) exacerbate the inflammatory process through the preferential expression and release of DC-derived IL-23 and the subsequent support of the autoreactive/inflammatory Th17 phenotype...
  39. ncbi Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system
    Guang Xian Zhang
    Department of Neurology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, USA
    J Immunol 170:2153-60. 2003
    ....
  40. pmc Production of interleukin-13 by human dendritic cells after stimulation with protein allergens is a key factor for induction of T helper 2 cytokines and is associated with activation of signal transducer and activator of transcription-6
    Iris Bellinghausen
    Department of Dermatology, University of Mainz, Mainz, Germany
    Immunology 108:167-76. 2003
    ..Taken together, DC-derived IL-13, which is released after exposure to allergens appears to be one of the critical factors for DC to acquire the capability to induce Th2 cytokine production...
  41. ncbi Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma
    Shuntaro Oniki
    Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
    Cancer Res 66:6395-404. 2006
    ..Our data support that IL-23 and IL-27 might play a role in future cytokine-based immunotherapy against poorly immunogenic tumors...
  42. pmc NKG2D recognition and perforin effector function mediate effective cytokine immunotherapy of cancer
    Mark J Smyth
    Cancer Immunology Program, Peter MacCallum Cancer Centre, Locked Bag 1, A Beckett St, 8006, Victoria, Australia
    J Exp Med 200:1325-35. 2004
    ....
  43. pmc Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments
    Ayuko Sato
    Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 101:16274-9. 2004
    ....
  44. ncbi IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells
    P Kalinski
    Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands
    J Immunol 159:28-35. 1997
    ..Since type 2 Th responses are protective in several Th1-related autoimmune disorders, PGE2-DC may be considered for use in immunotherapy...
  45. ncbi The roles of IL-12 in providing a third signal for clonal expansion of naive CD8 T cells
    Javier Valenzuela
    Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
    J Immunol 169:6842-9. 2002
    ....
  46. ncbi Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10
    C Sgadari
    Division of Hematologic Products, Food and Drug Administration, Bethesda, MD 20892, USA
    Blood 87:3877-82. 1996
    b>Interleukin 12 (IL-12), a multifunctional cytokine produced by macrophages and B-cell lines, induces interferon-gamma (IFN-gamma) production, stimulates growth of both T and natural killer cells, promotes Th1-type helper T-cell responses, ..
  47. pmc TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation
    Hidetoshi Takedatsu
    Inflammatory Bowel Disease Center, Cedars Sinai Medical Center, Los Angeles, California, USA
    Gastroenterology 135:552-67. 2008
    ..Expression of TL1A is increased in the mucosa of Crohn's disease patients and murine models of ileitis. The aim of this study was to determine the possible role of TL1A in chronic intestinal inflammation...
  48. pmc Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation
    Craig A Murphy
    Discovery Research, DNAX Research Inc, Palo Alto, CA 94304, USA
    J Exp Med 198:1951-7. 2003
    ..The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation...
  49. ncbi Generation of potent anti-tumor immunity in mice by interleukin-12-secreting dendritic cells
    Katharina Gabriele Hüttner
    Children s Cancer Research Institute, St Anna Children s Hospital, Kinderspitalgasse 6, 1090 Vienna, Austria
    Cancer Immunol Immunother 54:67-77. 2005
    ..Together these data provide evidence for the unique capacity of actively IL-12 secreting DCs to trigger effective anti-tumor immunity using exogenous tumor antigens...
  50. ncbi Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells
    S F Wolf
    Genetics Institute, Inc, Cambridge, MA 02140
    J Immunol 146:3074-81. 1991
    ..The synergistic stimulation by NKSF plus IL-2 of T and NK function supports the possibility that these cytokines might prove useful in cancer therapy...
  51. ncbi NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma
    M J Smyth
    Cancer Immunology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 8006, Australia
    Int Immunol 13:459-63. 2001
    ..In contrast, sarcoma incidence and growth rate were reduced using IL-12 therapy, this effect was mediated in the absence of T cells (including NKT cells), but not NK cells...
  52. ncbi Interleukin 12 induces T-cell recruitment into the atherosclerotic plaque
    Xiaoyu Zhang
    Department of Medicine, Kathleen B and Mason I Lowance Center for Human Immunology, Emory University School of Medicine, Atlanta, GA, USA
    Circ Res 98:524-31. 2006
    ....
  53. ncbi Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae
    Tom H M Ottenhoff
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Nat Genet 32:97-105. 2002
    ..Ten syndromes have thus far been identified. Recent insights in genetically controlled host defense and susceptibility to mycobacterial disease are discussed...
  54. pmc Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin 12 expression
    N A Giese
    Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 0760, USA
    J Exp Med 186:1535-46. 1997
    ..This indicates that ICSBP is a deciding factor in Th responses governing humoral and cellular immunity through its role in regulating IL-12 expression...
  55. ncbi IL-12 prevents mortality in mice infected with Histoplasma capsulatum through induction of IFN-gamma
    P Zhou
    Lymphokine Regulation Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 155:785-95. 1995
    ..Responses could be restored by adding inhibitors of IFN-gamma or of nitric oxide to the in vitro cultures. The above observations suggest that IL-12 may be useful in immunologic intervention against this opportunistic pathogen...
  56. ncbi Mechanism of CD1d-restricted natural killer T cell activation during microbial infection
    Manfred Brigl
    Division of Rheumatology, Immunology, and Allergy, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Immunol 4:1230-7. 2003
    ..Instead, weak responses to CD1d-presented self antigens were amplified by interleukin 12 made by dendritic cells in response to microbial products, resulting in potent interferon-gamma secretion...
  57. ncbi Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: outcome of a phase I study
    W K Kang
    Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    Hum Gene Ther 12:671-84. 2001
    A phase I dose-escalation clinical trial of peritumoral injections of interleukin 12 (IL-12)-transduced autologous fibroblasts was performed in patients with disseminated cancer for whom effective treatment does not exist...
  58. ncbi "Alternatively activated" dendritic cells preferentially secrete IL-10, expand Foxp3+CD4+ T cells, and induce long-term organ allograft survival in combination with CTLA4-Ig
    Yuk Yuen Lan
    Thomas E Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA
    J Immunol 177:5868-77. 2006
    ..These data enhance insight into the regulatory properties of AADC and demonstrate their therapeutic potential in vascularized organ transplantation...
  59. ncbi A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors
    Giuseppe Giaccone
    Department of Medical Oncology, Vrije Universiteit Medical Center, HV 1081 Amsterdam, The Netherlands
    Clin Cancer Res 8:3702-9. 2002
    ..We performed a dose escalation study of KRN7000 in advanced cancer patients...
  60. ncbi The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: effects of psychotropic drugs
    Y K Kim
    Department of Psychiatry, Korea University Ansan Hospital, College of Medicine, Korea
    Mol Psychiatry 7:1107-14. 2002
    ....
  61. ncbi Effect of 6-gingerol on pro-inflammatory cytokine production and costimulatory molecule expression in murine peritoneal macrophages
    Sudipta Tripathi
    Department of Surgery, SUNY Upstate Medical University, Syracuse, New York 13210, USA
    J Surg Res 138:209-13. 2007
    ....
  62. ncbi Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells
    Monica Rimoldi
    Department of Experimental Oncology, European Institute of Oncology, I 20141 Milan, Italy
    Nat Immunol 6:507-14. 2005
    ..Epithelial cell-conditioned dendritic cells released interleukins 10 and 6 but not interleukin 12, and they promoted the polarization of T cells toward a 'classical' noninflammatory T helper type 2 response, ..
  63. ncbi Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection
    Khuong B Nguyen
    Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA
    Science 297:2063-6. 2002
    ..Thus, type 1 IFNs, in addition to interleukin-12, provide pathways for innate regulation of adaptive immunity, and their immunoregulatory functions are controlled by modulating the activity of individual STATs...
  64. ncbi IL-4 and IL-10 antagonize IL-12-mediated protection against acute vaccinia virus infection with a limited role of IFN-gamma and nitric oxide synthetase 2
    M van Den Broek
    Institute for Experimental Immunology, Zurich, Switzerland
    J Immunol 164:371-8. 2000
    ..Thus, our results identify a new role for IL-12 in defense beyond the induction of IFN-gamma and show that IL-4 and IL-10 modulate host protective responses to VV...
  65. ncbi Aberrant production of IL-12 by macrophages from several autoimmune-prone mouse strains is characterized by intrinsic and unique patterns of NF-kappa B expression and binding to the IL-12 p40 promoter
    Jiajian Liu
    Arthritis Section, Department of Medicine, Boston University Medical Center, Boston MA 02118, USA
    J Immunol 169:581-6. 2002
    ....
  66. ncbi Mice with STAT6-targeted gene disruption develop a Th1 response and control cutaneous leishmaniasis
    L M Stamm
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    J Immunol 161:6180-8. 1998
    ..mexicana infection in genetically susceptible mice and demonstrate that in the absence of STAT6, susceptible mice default toward a Th1-like response and control cutaneous L. mexicana infection...
  67. pmc Hepatitis B virus surface antigen impairs myeloid dendritic cell function: a possible immune escape mechanism of hepatitis B virus
    Marjoleine L Op den Brouw
    Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands
    Immunology 126:280-9. 2009
    ..The direct immune regulatory effect of HBV and circulating HBsAg particles on the function of DC can be considered as part of the mechanism by which HBV escapes immunity...
  68. pmc Reciprocal activating interaction between natural killer cells and dendritic cells
    Franca Gerosa
    Department of Pathology, Section of Immunology, University of Verona, 37100 Verona, Italy
    J Exp Med 195:327-33. 2002
    ..These data demonstrated for the first time a bidirectional cross talk between NK cells and DC, in which NK cells activated by IL-2 or by mature DC induce DC maturation...
  69. pmc Recombinant interleukin 12 cures mice infected with Leishmania major
    F P Heinzel
    Department of Medicine, Case Western Reserve University, Cleveland, Ohio
    J Exp Med 177:1505-9. 1993
    ..Because interleukin 12 (IL-12) has potent T cell growth and interferon gamma (IFN-gamma) stimulatory effects, we studied its effect ..
  70. ncbi TLR agonists promote ERK-mediated preferential IL-10 production of regulatory dendritic cells (diffDCs), leading to NK-cell activation
    Cheng Qian
    Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiangyin Rd, Shanghai, 200433, People s Republic of China
    Blood 108:2307-15. 2006
    ..Our results illuminate signal pathways for the unique cytokine profile of diffDCs, and diffDCs can exert their regulatory function even after inflammatory stimuli, thus reflecting one way for strict regulation of immune response...
  71. ncbi Interleukin 15-dependent crosstalk between conventional and plasmacytoid dendritic cells is essential for CpG-induced immune activation
    Seiichi Kuwajima
    Department of Immunology, Akita University School of Medicine, Akita 010 8543, Japan
    Nat Immunol 7:740-6. 2006
    ..Interaction between CD40 on cDCs and CD40 ligand on pDCs led to IL-12 production by cDCs. Thus, IL-15-dependent crosstalk between cDCs and pDCs is essential for CpG-induced immune activation...
  72. pmc Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice
    P Nanni
    Cancer Research Section, Department of Experimental Pathology, University of Bologna, Italy
    J Exp Med 194:1195-205. 2001
    ..In conclusion, our data show that an allogeneic HER-2/neu-expressing cell vaccine combined with IL-12 systemic treatment can prevent the onset of genetically determined tumors...
  73. pmc Interferon gamma derived from CD4(+) T cells is sufficient to mediate T helper cell type 1 development
    A E Wakil
    Department of Medicine and the Department of Microbiology Immunology, University of California San Francisco, San Francisco, California 94143, USA
    J Exp Med 188:1651-6. 1998
    ..IFN-gamma) has been implicated in T helper type 1 (Th1) cell development through its ability to optimize interleukin 12 (IL-12) production from macrophages and IL-12 receptor expression on activated T cells...
  74. ncbi Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells
    Eva V Acosta-Rodriguez
    Institute for Research in Biomedicine, CH 6500 Bellinzona, Switzerland
    Nat Immunol 8:942-9. 2007
    ....
  75. pmc Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice
    S Trembleau
    Roche Milano Ricerche, Italy
    J Exp Med 181:817-21. 1995
    ..Administration of interleukin 12 (IL-12), a key cytokine which guides the development of T helper type 1 (Th1) CD4+ T cells, induces rapid ..
  76. ncbi The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma
    Moneeb Ehtesham
    Maxine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, California 90048, USA
    Cancer Res 62:5657-63. 2002
    ..particularly against disseminating tumor pockets, we inoculated intracranial glioma-bearing mice with interleukin 12 (IL-12) producing NSCs...
  77. pmc In vivo natural killer cell activities revealed by natural killer cell-deficient mice
    S Kim
    Howard Hughes Medical Institute, Rheumatology Division, Box 8045, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 97:2731-6. 2000
    ....
  78. ncbi In the absence of endogenous IFN-gamma, mice develop unimpaired IL-12 responses to Toxoplasma gondii while failing to control acute infection
    T M Scharton-Kersten
    Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 157:4045-54. 1996
    ..gondii: IL-12 precedes and initiates synthesis of IFN-gamma, while the latter lymphokine directly controls parasite growth and diminishes the contribution of IL-4- and IL-5-producing T cell subsets...
  79. ncbi Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae
    Esther van de Vosse
    Department of Infectious Diseases, Leiden University Medical Centre, Leiden, Netherlands
    Lancet Infect Dis 4:739-49. 2004
    ..to interferon gamma, due to deleterious mutations in genes that encode major proteins in the type 1 cytokine (interleukin 12/interleukin 23/interferon gamma) axis (interleukin 12p40/interleukin 23p40, IL12 receptor beta1/IL23 receptor ..
  80. ncbi Innate immune response to malaria: rapid induction of IFN-gamma from human NK cells by live Plasmodium falciparum-infected erythrocytes
    Katerina Artavanis-Tsakonas
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    J Immunol 169:2956-63. 2002
    ....
  81. ncbi The role of IL-12 in maintaining resistance to Leishmania major
    Audrey Y Park
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104 Department of Environmental Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland
    J Immunol 168:5771-7. 2002
    ....
  82. ncbi Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response
    Sudipta Bhowmick
    Infectious Diseases Division, Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Jadavpur, Kolkata 700032, India
    Vaccine 25:6544-56. 2007
    ..These findings suggest that an immune modulation towards Th1 is effective for both successful vaccination and immunotherapy...
  83. ncbi Distinct CpG DNA and polyinosinic-polycytidylic acid double-stranded RNA, respectively, stimulate CD11c- type 2 dendritic cell precursors and CD11c+ dendritic cells to produce type I IFN
    N Kadowaki
    Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA
    J Immunol 166:2291-5. 2001
    ....
  84. ncbi Partial impairment of cytokine responses in Tyk2-deficient mice
    M Karaghiosoff
    Institute of Animal Breeding and Genetics, Veterinary University of Vienna, Austria
    Immunity 13:549-60. 2000
    ..Tyk2-/- mice are unable to clear vaccinia virus and show a reduced T cell response after LCMV challenge. These data imply a selective contribution of Tyk2 to the signals triggered by various biological stimuli and cytokine receptors...
  85. ncbi The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses
    Giorgio Trinchieri
    Schering Plough Research Institute, Laboratory for Immunological Research, 69571 Dardilly, France
    Immunity 19:641-4. 2003
    ..2003; Villarino et al., 2003), indicate that they mediate complex and well-differentiated functions...
  86. ncbi Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes
    Amy E Lovett-Racke
    Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 USA
    Immunity 21:719-31. 2004
    ..Since T-bet regulates IFNgamma production in CD4(+) T cells, but to a lesser extent in most other IFNgamma-producing cells, T-bet may be a target for therapeutics for Th1-mediated diseases...
  87. pmc Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration
    A C Inge Boullart
    Department of Tumor Immunology, Nijmegen Centre for Molecular Life Science, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    Cancer Immunol Immunother 57:1589-97. 2008
    ..We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter...
  88. ncbi HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation
    Anna Smed-Sorensen
    Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, F59 Karolinska University Hospital Huddinge, S 141 86 Stockholm, Sweden
    Blood 104:2810-7. 2004
    ..CD40L stimulation induced significant secretion of tumor necrosis factor alpha (TNFalpha) and interleukin 12 (IL-12) p70 from both HIV-1-exposed and unexposed DCs...
  89. ncbi Characteristics of intestinal dendritic cells in inflammatory bowel diseases
    Ailsa L Hart
    Antigen Presentation Research Group, Imperial College London, England
    Gastroenterology 129:50-65. 2005
    ..We aimed to identify changes in intestinal DCs that may underlie the dysregulated immune response to enteric bacteria that occurs in patients with inflammatory bowel disease (IBD)...
  90. pmc Interleukin-12 in infectious diseases
    L Romani
    Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy
    Clin Microbiol Rev 10:611-36. 1997
    ..Continued investigation into the possible application of IL-12 therapy to human infections is warranted by the role of the cytokine in inflammation, immunopathology, and autoimmunity...
  91. ncbi Dendritic cells are host cells for mycobacteria in vivo that trigger innate and acquired immunity
    Xinan Jiao
    Unité de Biologie des Régulations Immunitaires, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France
    J Immunol 168:1294-301. 2002
    ..Strikingly, BCG bacilli survive but remain stable in number in the DC leukocyte subset during the first 2 wk of infection. As Ag presentation by DC is rapidly lost, this suggests that DC may represent a hidden reservoir for mycobacteria...
  92. ncbi The polarization of T(h)1/T(h)2 balance is dependent on the intracellular thiol redox status of macrophages due to the distinctive cytokine production
    Yukie Murata
    Basic Research Laboratories, Ajinomoto Co Inc, 1 1 Suzuki cho, Kawasaki ku, Kawasaki 210 0861, Japan
    Int Immunol 14:201-12. 2002
    ..The findings implicate that the alteration in Mp functions because altered intracellular glutathione may play a relevant role in the pathological progression of inflammation...
  93. ncbi Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production
    T Ghayur
    BASF Bioresearch Corporation, Worcester, Massachusetts 01605 4314, USA
    Nature 386:619-23. 1997
    ..Specific caspase-1 inhibitors would provide a new class of anti-inflammatory drugs with multipotent action...
  94. ncbi IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination
    Bruno Gran
    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Immunol 169:7104-10. 2002
    ..These data demonstrate a redundancy of the IL-12 system in the induction of EAE and suggest that p40-related heterodimers, such as the recently cloned IL-23 (p40p19), may play an important role in disease pathogenesis...
  95. ncbi Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu
    K Nakanishi
    Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1 1, Mukogawa cho, Nishinomiya, Hyogo 663 8501, Japan
    Cytokine Growth Factor Rev 12:53-72. 2001
    ..Moreover, IL-18 also induces IL-13 and/or IL-4 production by NK cells, mast cells and basophils. Therefore, IL-18 should be seen as a unique cytokine that enhances innate immunity and both Th1- and Th2-driven immune responses...
  96. ncbi Cutting edge: IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells
    Hideki Tsujimura
    Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 170:1131-5. 2003
    ..ICSBP-restored DCs produced IFN-alpha and IL-12p40 in a DC subset-selective manner with the amounts comparable to those by +/+ DCs. Together, ICSBP is essential for early pDC development and final maturation of both pDCs and mDCs...
  97. pmc Two roads diverged: interferon alpha/beta- and interleukin 12-mediated pathways in promoting T cell interferon gamma responses during viral infection
    L P Cousens
    Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA
    J Exp Med 189:1315-28. 1999
    ....
  98. pmc Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris
    Edmund Lee
    Laboratory for Investigative Dermatology, The Rockefeller University Hospital, P O Box 178, 1230 York Avenue, New York, NY 10021, USA
    J Exp Med 199:125-30. 2004
    ..Our data suggest that IL-23 is playing a more dominant role than IL-12 in psoriasis, a Th1 type of human inflammatory disease...
  99. ncbi IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells
    Stefan Pflanz
    DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA
    Immunity 16:779-90. 2002
    ..It also strongly synergizes with IL-12 to trigger IFN-gamma production of naive CD4(+) T cells. IL-27 mediates its biologic effects through the orphan cytokine receptor WSX-1/TCCR...
  100. ncbi Critical role of MHC class I-related chain A and B expression on IFN-alpha-stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection
    Masahisa Jinushi
    Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    J Immunol 170:1249-56. 2003
    ..These findings suggested that MICA/B induction on DCs may be one of the mechanisms by which IFN-alpha activates NK cells; this impairment might affect IFN-alpha responsiveness in hepatitis C virus infection...
  101. ncbi Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences
    Robert D Stout
    Department of Microbiology and Immunology, University of Louisville School of Medicine, Health Sciences Center, Louisville, KY 40292, USA
    J Immunol 175:342-9. 2005
    ....

Research Grants69

  1. Anti-Inflammatory Glycosaminoglycan Ethers for Treatment of Periodontitis
    JUSTIN RODNEY SAVAGE; Fiscal Year: 2011
    ..We propose to develop anionic, partially lipophilic hyaluronic acid derivatives as a simple mechanistically-based treatment for this chronic extraordinarily common dental disorder. ..
  2. Dietary Risk for Colon Cancer in the Mouse
    Leonard H Augenlicht; Fiscal Year: 2013
    ..abstract_text> ..
  3. Inhibition of CCR1/CCR5 mediated angiogenesis and joint destruction by EGCG
    Salah Uddin Ahmed; Fiscal Year: 2010
    ..The success of the proposed experiments may lead to a significant advancement in the development of EGCG as a potentially safe and inexpensive treatment option for RA. ..
  4. Effects of Metabolic Disorders on Bone Marrow-Derived Cell Function
    Gina C Schatteman; Fiscal Year: 2012
    ..e., diabetic mice with metabolic syndrome) we identified four molecules, tumor necrosis factor alpha (TNF1), interleukin 12 (IL-12), monocyte chemoattractant factor 1 (MCP-1), and vascular endothelial growth factor A (VEGF-A) that ..
  5. Neurotoxicity of Magnetic Nanoparticles
    Veronica Shubayev; Fiscal Year: 2010
    ....
  6. Mitogen-activated Protein Kinases and NF-kB Activation in Vascular Smooth Muscle
    Bingbing Jiang; Fiscal Year: 2010
    ....
  7. IL12 Gene Therapy For Enhancing Therapeutic Efficacy of Bleomycin Against Oral Tu
    Shulin Li; Fiscal Year: 2013
    ..abstract_text> ..
  8. Function of metal transporter ZIP14 as regulated by proinflammatory stimuli
    Robert J Cousins; Fiscal Year: 2013
    ..These may benefit from zinc supplementation or drugs designed to influence ZIP14 activity. ..
  9. Role of the Interleukin12/STAT4 Pathway in Insulin Resistance and Atherosclerosis
    Jerry L Nadler; Fiscal Year: 2013
    ..The completed project should identify an innovative therapeutic target that could lead to new treatment to reduce atherosclerosis associated with central obesity insulin resistance and diabetes. ..
  10. Novel Nanopolymers to Inhibit Angiogenesis and Increase the Anti-tumor Immunity
    Manuel L Penichet; Fiscal Year: 2013
    ..A novel nanobiopolymer-based therapy against HER2/neu expressing cancer cells with sufficient capacity to inhibit angiogenesis and orchestrate an anti-tumor immune response should make a significant clinical impact. ..
  11. Early Environmental Hygiene and Pediatric Asthma
    Christine C Johnson; Fiscal Year: 2009
    ..If factors associated with animal or endotoxin contact are related to asthma risk, such factors would likely lend themselves to public health interventions. ..
  12. Delta-like ligand 4+ dendritic cells and induction of alloimmunity
    Yi Zhang; Fiscal Year: 2013
    ....
  13. Cell Differentation During Decidualization
    Zuzana Strakova; Fiscal Year: 2010
    ..Thus, in the long term our studies might provide new targets of intervention leading to improvements in diagnosis and treatment. ..
  14. Involvement of Natural Killer T cells in Hepatic Fibrogenesis
    Ian N Hines; Fiscal Year: 2011
    ..Together, these studies will provide new insight into the mechanisms of T cell-mediated hepatic fibrosis. ..
  15. A her-2/neu Pulsed DC1 Vaccine for Patients with DCIS
    BRIAN JOSEPH CZERNIECKI; Fiscal Year: 2012
    ..It is anticipated that the production of chemokines and cytokines by DC1 will lead to accelerated accumulation of specific and non-specific effectors in the area of DCIS and further clinical responses. ..
  16. TLR7 mediates immune cell infiltration and homing to combat West Nile virus infec
    Fengwei Bai; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: This project is to dissect the mechanisms underlying Toll-like Receptor 7- mediated immune cell infiltration and homing to combat West Nile virus infection in the murine model of West Nile virus encephalitis. ..
  17. Corticosteroids for Children with Febrile Urinary Tract Infections
    Nader Shaikh; Fiscal Year: 2013
    ..count, erythrocyte sedimentation rate, interleukin 6, interleukin 8, macrophage migration inhibitory factor, interleukin 12, transforming growth factor 21) to develop a prediction rule that accurately identifies children at risk for ..
  18. Persistent COMT-dependent Pain: Role of beta-adrenergic Receptors
    ANDREA G NACKLEY NEELY; Fiscal Year: 2013
    ..g., beta2- and beta3ARs) for development of effective therapies for patients with persistent pain conditions.]] ..
  19. Hepatic lymphocytes and fatty liver disease
    Michael D Wheeler; Fiscal Year: 2010
    ..The mechanisms regulating the transition from steatohepatitis to fibrosis are unknown. Here, we will investigate the role of T lymphocytes and the production of T cell derived cytokines in fibrogenesis. ..
  20. Inflammasome regulation after spinal cord injury
    Robert W Keane; Fiscal Year: 2012
    ..The development of new treatments that can be given in the first hours after SCI may prevent or reverse much of the spinal cord damage resulting from SCI with a goal of restoring normal functioning in behavior. ..
  21. Transgenic Mouse Model to Address Heterogeneity in Autism Spectrum Disorders
    RANDY DEAN BLAKELY; Fiscal Year: 2010
    ..Based on exciting preliminary evidence that mice expressing Ala56 SERT exhibit multiple behavioral and biochemical phenotypes, we propose a two-year project to extend our studies and dissect the impact of SERT hyperfunction in vivo. ..
  22. Social Stress Modulates Neuropeptide Y in a Model fo Periodontal Inflammation
    BRENDA FAYE READER; Fiscal Year: 2013
    ..Exploring the specific mechanisms of periodontal inflammation and [bone resorption] will aid in identifying novel therapeutic targets that will improve the clinical outcomes of chronic periodontitis. ..
  23. ACTIVATION OF NF-KB IN GLIAL CELLS AND CNS OF EAE
    Kalipada Pahan; Fiscal Year: 2009
    ..In summary, the results obtained from this proposal will characterize molecular mechanisms for novel biological functions of p40-2 and p40 and delineate their role in the neuroinflammatory disease process of EAE. ..
  24. Engineered HSV For Treatment of Malignant Glioma
    Richard J Whitley; Fiscal Year: 2013
    ..abstract_text> ..
  25. Regulation of Caspase-1 Signaling and Inflammation by the P2X7 ATP Receptor
    George R Dubyak; Fiscal Year: 2013
    ..These studies will provide mechanistic insights that may facilitate development of adjuvant purinergic receptor-based therapies which increase the efficacy of immunogenic anti-tumor responses to primary cancer chemotherapeutic agents. ..
  26. Gene Therapy and Radiation Therapy for Prostate Cancer
    Svend O Freytag; Fiscal Year: 2013
    ..added a fourth modality to our investigational approach by generating a third-generation adenovirus armed with interleukin 12 (IL-12) that has the potential to eradicate both local and metastatic disease...
  27. M.tuberculosis-induced Alternative Processing of IL12RB1 mRNA
    Richard Robinson; Fiscal Year: 2013
    ....
  28. Chitosan-based Delivery and Immunopotentiation of Cancer Vaccines
    David Zaharoff; Fiscal Year: 2012
    ..This project will study the mechanisms by which chitosan enhances the antitumor activity of IL-12 and support the potential clinical translation of chitosan/IL- 12 immunotherapy. ..
  29. Genome-wide dissection of Mendelian susceptibility to mycobacterial disease
    Jean Laurent Casanova; Fiscal Year: 2013
    ..Nearly half the patients with MSMD lack a genetic etiology. We hypothesize that MSMD in these patients also results from inborn errors of immunity, which we aim to identify using hypothesis- free, GW approaches. ..
  30. Investigating the Role of IL35 in Anti-Tumor Immunity
    Meghan E Turnis; Fiscal Year: 2013
    ..Research on these Aims should yield exciting knowledge that will advance the field and hopefully prove to be therapeutically beneficial. ..
  31. Trigeminal - RVM involvement in bilateral deep tissue orofacial hyperalgesia
    Bryan Chai; Fiscal Year: 2012
    ..Through better understanding of the pathways and mechanisms involved in deep tissue pain facilitation to the contralateral side, novel therapies and strategies may be developed for orofacial pain disorders. ! ..
  32. Novel ways to prevent upper GT infection
    Kathleen A Kelly; Fiscal Year: 2013
    ....
  33. Combination gene therapy for metastatic colon cancer
    Shu Hsia Chen; Fiscal Year: 2010
    ..The completion of these studies will not only provide a new insight into the mechanisms of tumor mediated suppression and tolerance, but also facilitate effective clinical translation of our immune enhancing therapy. ..
  34. Inflammation Pathways in Breast Cancer
    Margaret M Madeleine; Fiscal Year: 2010
    ..Cytokine genes are expressed at different levels in older compared to younger women;therefore, we will also evaluate their contribution to breast cancer risk by levels of common exposures such as obesity and HRT use. ..
  35. REGULATION OF B CELL FUNCTION BY INTERLEUKIN 12
    Dennis W Metzger; Fiscal Year: 2011
    ..The ultimate goal is to exploit the information obtained in order to understand the requirements for induction of protective pulmonary immunity and to design effective mucosal vaccine adjuvants for use in humans. ..
  36. Dietary modulation of mammary tumorigenesis in the PymT model
    Lidija Klampfer; Fiscal Year: 2012
    ....
  37. Integrating innate and adaptive immunity in cancer therapy
    Nejat K Egilmez; Fiscal Year: 2013
    ..abstract_text> ..
  38. Anti-IL-12p40 Treatment of CVID Enteropathy: Gene Expression/Microbiota Analysis
    Warren Strober; Fiscal Year: 2013
    ....
  39. A genetic dissection of Mendelian susceptibility to mycobacterial diseases (MSMD)
    Jean Laurent Casanova; Fiscal Year: 2013
    ..Finally, the genetic dissection of MSMD will pave the way for the genetic dissection of severe tuberculosis in otherwise healthy children. ..
  40. CD147 as a Novel Target in Head and Neck Cancer
    Eben L Rosenthal; Fiscal Year: 2013
    ..Furthermore, novel molecular mechanisms by which CD147 acts to promote the malignant phenotype in vitro and in vivo will be investigated. ..
  41. Phase 1 Study of Resiquimod Gel Therapy for Cutaneous T-Cell Lymphoma
    Alain H Rook; Fiscal Year: 2013
    ....
  42. Ceramide and acute phase protein elevation during aging
    Mariana Nikolova-Karakashian; Fiscal Year: 2013
    ..In the past we reported that the hepatic response to Interleukin 12 (IL-12), a major mediator of systemic inflammation, is augmented during aging leading to excessive production ..
  43. PROTECTIVE ANTIGENS FROM HISTOPLASMA CAPSULATUM
    GEORGE DEEPE; Fiscal Year: 2007
    ..abstract_text> ..
  44. Phase 2 of EGEN-001 for Tx of Chemotherapy-Resistant Recurrent Ovarian Cancer
    Khursheed Anwer; Fiscal Year: 2013
    ..GOG has approved conducting the study in conjunction with EGEN. A Phase II protocol (DTM 0835) is under development at GOG. ..
  45. TH1 CYTOKINES AND IMPAIRED CD8* CTLS IN ELDERLY
    Innocent Mbawuike; Fiscal Year: 2001
    ..The Th1 cytokines, such as interferon gamma (IFN-g), interleukin 2 (IL-2) and interleukin 12 (IL-12), favor the induction of CD8+ CTLs while Th2 cytokines, such as interleukin 4 (IL-4) and interleukin 10 ..
  46. Effects of acupuncture on chemotherapy-induced pain
    Ruixin Zhang; Fiscal Year: 2009
    ..This study will evaluate the effects and mechanisms of electroacupuncture (EA) on such pain in a rat model. The success of the proposed study will greatly advance the management of CIP. ..
  47. De novo engineering of protein agonists and antagonists
    CASIM SARKAR; Fiscal Year: 2013
    ..More generally, these methods will not only enable the production of new therapeutics, but will also provide unique insights into the basic requirements for specific, high-affinity protein recognition. ..
  48. PARACRINE REGULATION: SERTOLI/GERM CELL INTERACTIONS
    DR PATRICIA MORRIS; Fiscal Year: 2003
    ..abstract_text> ..
  49. CYTOKINE RESPONSE IN FIV AND SIV IMMUNODEFICIENCY
    Gregg Dean; Fiscal Year: 2002
    ..ft. of laboratory space, startup funds, access to the central equipment laboratory, and three years of support for a technical assistant. ..
  50. Interferon gamma in autoimmune thyroiditis & thyroid function
    Patrizio Caturegli; Fiscal Year: 2007
    ..We also hypothesize that augmented TSH signaling is required to induce the adipocyte-rich phenotype, and cross thyr-IFNg transgenics to TSH receptor knockout mice. ..
  51. MECHANISMS OF PULMONARY FIBROSIS CAUSED BY SILICA
    Gerald Davis; Fiscal Year: 2003
    ..And other interstitial lung diseases where the cause is not known and treatment is not effective. ..
  52. Chemokine Signaling and Colitis in Gia2 Deficient Mice
    Robert Edwards; Fiscal Year: 2006
    ..This application has the support of outstanding mentors at two institutions, and funding of this application will foster Dr Edwards' continued development as a physician-scientist. ..
  53. Sphingosine Kinase Inhibitors as Anti-Arthritis Agents
    Leo Fitzpatrick; Fiscal Year: 2009
    ..In this project, we have developed inhibitors of SK and shown them to have therapeutic efficacy in arthritis models. Continued development of these compounds may provide important new drugs for the treatment of arthritis. ..
  54. BIOADHESIVE MICROSPHERES FOR COLON CANCER THERAPY
    NEJAT EGILMEZ; Fiscal Year: 2002
    ..abstract_text> ..
  55. Biobehavioral-Cytokine Interactions in Ovarian Cancer
    Susan Lutgendorf; Fiscal Year: 2007
    ..Findings will have implications for innovative behavioral and pharmacological intervention strategies for ovarian cancer patients. ..
  56. CHARACTERIZATION/MODULATION OF CYTOKINE RESPONSES IN FIV
    Gregg Dean; Fiscal Year: 2001
    ..Understanding the role of the cytokines in the pathogenesis, therapy, and vaccination in FIV infection will have direct implications for HIV infection. ..
  57. MECHANISMS OF IMMUNITY TO VIRAL VACCINES IN INFANCY
    Hayley Gans; Fiscal Year: 2004
    ..Purified proteins will be used in assays for T-cell proliferation and cytokine production, to determine if specific proteins drive Th1 versus Th2-like CD4+ T-cell responses. ..
  58. REGULATION OF THL RESPONSES IN PULMONARY SARCOIDOSIS
    DAVID MOLLER; Fiscal Year: 2000
    ..Thus, these studies may assist in the development of new therapies designed to halt the granulomatous and fibrotic responses that lead to end-stage pulmonary disease in sarcoidosis. ..
  59. Phase I Trial of Herceptin Plus IL12
    William Carson; Fiscal Year: 2003
    ..These studies will provide information on the actions of Herceptin and IL-12, enhance our ability to monitor the effects of antibody-based therapies, and permit the identification of specific markers of responsiveness. ..
  60. INTERLEUKIN 12 AS IMMUNOTHERAPY IN LEISHMANIASIS
    FREDERICK HEINZEL; Fiscal Year: 2001
    ....
  61. Phase ii intraperitoneal rhIL 12
    Ralph Freedman; Fiscal Year: 2002
    ..4) Determine whether expression of proangiogenic factors VEGF, FGF2 and IL-8 are decreased following IF rhIL- 12. ..
  62. PHASE I/II STUDIES OF EGEN-001 THERAPY FOR OVARIAN CANCER
    ANWER KHURSHEED; Fiscal Year: 2009
    ..The proposed research is anticipated to result in a safer and more efficacious treatment modality for ovarian cancer due to its ability to enhance the body's natural ability to fight off cancer. ..
  63. REGULATION OF IL 12 IN MUCOSAL IMMUNITY AND IBD
    Scott Plevy; Fiscal Year: 1999
    ..These mechanisms may then be exploited to alter host immunity in infectious and inflammatory disorders, including IBD. ..
  64. IL-12 Gene Therapy for Metastatic Osteosarcoma
    Laura Worth; Fiscal Year: 2007
    ..Successful completion of these studies will result in a better understanding of the role the immune system (when activated with IL-12 and T cells receptor agonists). ..
  65. Immunogenetics of Cervical Cancer A Family-Based Design
    Stephen Schwartz; Fiscal Year: 2005
    ..b>Interleukin 12 (IL12) is a cytokine that promotes a cell-mediated response by activating macrophages and natural killer cells ..
  66. DEVELOPMENT OF NOVEL CORRELATIVE STUDIES FOR A PHASE I
    William Carson; Fiscal Year: 2000
    ....
  67. INTERLEUKIN 12 THERAPY OF CUTANEOUS T CELL LYMPHOMA
    Alain Rook; Fiscal Year: 2000
    ....
  68. PEPTIDE TARGETING OF IL12 TO MALIGNANT ENDOTHELIUM
    STUART HELFAND; Fiscal Year: 2002
    ..abstract_text> ..
  69. MECHANISM OF IL-12 INHIBITION BY CANDIDA ALBICANS
    Mahmoud Ghannoum; Fiscal Year: 2009
    ..Data obtained from these studies will lead to a better understanding of the complex immune response to CA infection and may identify novel prevention/treatment strategies for candidiasis. ..