caspase 1

Summary

Summary: A member of the caspase family that is highly specific for interleukin-1beta (INTERLEUKIN-1). It plays a role in inflammation and mammalian APOPTOSIS. Interleukin-1beta converting enzyme is frequently abbreviated ICE. EC 3.4.22.36

Top Publications

  1. ncbi Gout-associated uric acid crystals activate the NALP3 inflammasome
    Fabio Martinon
    Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
    Nature 440:237-41. 2006
  2. ncbi Immunological and inflammatory functions of the interleukin-1 family
    Charles A Dinarello
    Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado 80045, USA
    Annu Rev Immunol 27:519-50. 2009
  3. ncbi Cryopyrin activates the inflammasome in response to toxins and ATP
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 440:228-32. 2006
  4. pmc Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome
    Kiichi Nakahira
    Division of Pulmonary and Critical Care Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Nat Immunol 12:222-30. 2011
  5. ncbi The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta
    Fabio Martinon
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Mol Cell 10:417-26. 2002
  6. ncbi Non-canonical inflammasome activation targets caspase-11
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech Inc, South San Francisco, California 94080, USA
    Nature 479:117-21. 2011
  7. ncbi Inflammasomes in health and disease
    Till Strowig
    Department of Immunobiology, Yale University, Connecticut 06520, USA
    Nature 481:278-86. 2012
  8. pmc Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington, USA
    Nat Immunol 11:1136-42. 2010
  9. pmc AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
    Veit Hornung
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 458:514-8. 2009
  10. pmc The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis
    Luigi Franchi
    Department of Pathology, Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nat Immunol 10:241-7. 2009

Research Grants

Detail Information

Publications292 found, 100 shown here

  1. ncbi Gout-associated uric acid crystals activate the NALP3 inflammasome
    Fabio Martinon
    Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
    Nature 440:237-41. 2006
    ..These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases...
  2. ncbi Immunological and inflammatory functions of the interleukin-1 family
    Charles A Dinarello
    Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, Colorado 80045, USA
    Annu Rev Immunol 27:519-50. 2009
    ....
  3. ncbi Cryopyrin activates the inflammasome in response to toxins and ATP
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 440:228-32. 2006
    ..Therefore, cryopyrin is essential for inflammasome activation in response to signalling pathways triggered specifically by ATP, nigericin, maitotoxin, S. aureus or L. monocytogenes...
  4. pmc Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome
    Kiichi Nakahira
    Division of Pulmonary and Critical Care Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Nat Immunol 12:222-30. 2011
    ..Our study suggests that autophagic proteins regulate NALP3-dependent inflammation by preserving mitochondrial integrity...
  5. ncbi The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta
    Fabio Martinon
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Mol Cell 10:417-26. 2002
    ..Thus, the inflammasome constitutes an important arm of the innate immunity...
  6. ncbi Non-canonical inflammasome activation targets caspase-11
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech Inc, South San Francisco, California 94080, USA
    Nature 479:117-21. 2011
    ..These data highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections...
  7. ncbi Inflammasomes in health and disease
    Till Strowig
    Department of Immunobiology, Yale University, Connecticut 06520, USA
    Nature 481:278-86. 2012
    ..We review the functions of the different inflammasome complexes and discuss how aberrations in them are implicated in the pathogenesis of human diseases...
  8. pmc Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington, USA
    Nat Immunol 11:1136-42. 2010
    ..This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system...
  9. pmc AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
    Veit Hornung
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nature 458:514-8. 2009
    ..Collectively, these observations identify AIM2 as a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and ASC to activate caspase-1...
  10. pmc The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis
    Luigi Franchi
    Department of Pathology, Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nat Immunol 10:241-7. 2009
    ..Thus, understanding inflammasome pathways may provide insight into disease pathogenesis that might identify potential targets for therapeutic intervention...
  11. ncbi Biologic basis for interleukin-1 in disease
    C A Dinarello
    Department of Medicine, Tufts University, Boston, MA USA
    Blood 87:2095-147. 1996
    ..At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease...
  12. pmc The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
    Vijay A K Rathinam
    Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Nat Immunol 11:395-402. 2010
    ..Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity...
  13. ncbi Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf
    Sanjeev Mariathasan
    Molecular Oncology Department, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 430:213-8. 2004
    ..Notably, cell death triggered by stimuli that engage caspase-1 was ablated in macrophages lacking either ASC or Ipaf, suggesting a coupling between the inflammatory and cell death pathways...
  14. ncbi The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus
    Yue Zhao
    Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
    Nature 477:596-600. 2011
    ....
  15. ncbi Type I interferon inhibits interleukin-1 production and inflammasome activation
    Greta Guarda
    Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
    Immunity 34:213-23. 2011
    ..Our findings may thus explain the effectiveness of type I IFN in the treatment of inflammatory diseases but also the observed "weakening" of the immune system after viral infection...
  16. pmc Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor
    Pablo Pelegrin
    Department of Biomedical Science, University of Sheffield, Sheffield, UK
    EMBO J 25:5071-82. 2006
    ....
  17. ncbi Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf
    Edward A Miao
    Institute for Systems Biology, Seattle, Washington 98103, USA
    Nat Immunol 7:569-75. 2006
    ....
  18. pmc Caspase-1-induced pyroptotic cell death
    Edward A Miao
    Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Immunol Rev 243:206-14. 2011
    ..We further review the importance of pyroptosis in vivo as a potent mechanism to clear intracellular pathogens...
  19. pmc Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity
    Eric M Kofoed
    Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Nature 477:592-5. 2011
    ..cytosolic multiprotein complexes that initiate innate immune responses to pathogenic microbes by activating the caspase 1 protease...
  20. pmc Pyroptosis: host cell death and inflammation
    Tessa Bergsbaken
    Department of Microbiology, University of Washington, Seattle, Washington 98195, USA
    Nat Rev Microbiol 7:99-109. 2009
    ..Pyroptosis, or caspase 1-dependent cell death, is inherently inflammatory, is triggered by various pathological stimuli, such as stroke, ..
  21. ncbi Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
    D W Nicholson
    Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada
    Nature 376:37-43. 1995
    ..A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death...
  22. ncbi Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1beta in salmonella-infected macrophages
    Luigi Franchi
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Nat Immunol 7:576-82. 2006
    ..Thus, detection of flagellin through Ipaf induces caspase-1 activation independently of Toll-like receptor 5 in salmonella-infected and lipopolysaccharide-tolerized macrophages...
  23. pmc P2X7 receptor and caspase 1 activation are central to airway inflammation observed after exposure to tobacco smoke
    Suffwan Eltom
    Respiratory Pharmacology, Airway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom
    PLoS ONE 6:e24097. 2011
    ..The aim of this study was to determine whether activation of the P2X7/caspase 1 pathway has a functional role in CS-induced airway inflammation...
  24. pmc Glyburide inhibits the Cryopyrin/Nalp3 inflammasome
    Mohamed Lamkanfi
    Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA
    J Cell Biol 187:61-70. 2009
    ..Therefore, glyburide is the first identified compound to prevent Cryopyrin activation and microbial ligand-, DAMP-, and crystal-induced IL-1beta secretion...
  25. pmc Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity
    Tao Ren
    Genetics Department, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Pathog 2:e18. 2006
    ..It thus appears that macrophages sense cytosolic flagellin via a TLR5-independent pathway that leads to rapid caspase-1-dependent cell death and provides defense against intracellular bacterial pathogens...
  26. ncbi NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder
    Laetitia Agostini
    Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Immunity 20:319-25. 2004
    ..Macrophages from Muckle-Wells patients spontaneously secrete active IL-1beta. Increased inflammasome activity is therefore likely to be the molecular basis of the symptoms associated with NALP3-dependent autoinflammatory disorders...
  27. pmc The pannexin 1 channel activates the inflammasome in neurons and astrocytes
    William R Silverman
    Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 284:18143-51. 2009
    ..Thus, in contrast to macrophages and monocytes in which low intracellular K(+) has been suggested to trigger inflammasome activation, in neural cells, high extracellular K(+) activates caspase-1 probably through pannexin 1...
  28. ncbi Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence
    Olaf Gross
    III Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, Ismaninger Str 22, 81675 Munich, Germany
    Nature 459:433-6. 2009
    ..Thus, our results demonstrate the molecular basis for IL-1beta production after fungal infection and identify a crucial function for the Nlrp3 inflammasome in mammalian host defence in vivo...
  29. pmc Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing
    Petr Broz
    Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA
    Cell Host Microbe 8:471-83. 2010
    ..Our results suggest the formation of spatially and functionally distinct inflammasomes complexes in response to bacterial pathogens...
  30. ncbi Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors
    Francois Ghiringhelli
    Institut National de la Sante et de la Recherche Medicale, U805, Villejuif, France
    Nat Med 15:1170-8. 2009
    ..These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells...
  31. ncbi Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases
    Alexander U Lüthi
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland
    Immunity 31:84-98. 2009
    ..Thus, caspase-mediated proteolysis acts as a switch to dampen the proinflammatory properties of IL-33...
  32. ncbi Molecular mechanism of NLRP3 inflammasome activation
    Chengcheng Jin
    Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, TAC S 560, New Haven, CT 06520, USA
    J Clin Immunol 30:628-31. 2010
    ..Three signaling pathways involving potassium efflux, generation of reactive oxygen species, and cathepsin B release are discussed...
  33. pmc A Yersinia effector protein promotes virulence by preventing inflammasome recognition of the type III secretion system
    Igor E Brodsky
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    Cell Host Microbe 7:376-87. 2010
    ..These data demonstrate that a class of bacterial proteins interferes with cellular recognition of bacterial secretion systems and contributes to bacterial survival within host tissues...
  34. pmc ATP activates a reactive oxygen species-dependent oxidative stress response and secretion of proinflammatory cytokines in macrophages
    Cristiane M Cruz
    School of Natural Sciences, University of California, Merced, California 95344, USA
    J Biol Chem 282:2871-9. 2007
    ....
  35. ncbi Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages
    Susan L Fink
    Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA
    Cell Microbiol 8:1812-25. 2006
    ..This mechanism of caspase-1-mediated cell death provides additional experimental evidence supporting pyroptosis as a novel pathway of inflammatory programmed cell death...
  36. pmc NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta
    Florian R Greten
    Second Department of Medicine, Klinikum rechts der Isar, Technical University Munich, 81675 Germany
    Cell 130:918-31. 2007
    ..These results unravel an unanticipated role for IKKbeta-dependent NF-kappaB signaling in the negative control of IL-1beta production and highlight potential complications of long-term IKKbeta inhibition...
  37. ncbi The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection
    Dario S Zamboni
    Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA
    Nat Immunol 7:318-25. 2006
    ..These results establish Birc1e as a nucleotide-binding oligomerization-leucine-rich repeat protein involved in the detection and control of intracellular L. pneumophila...
  38. ncbi Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1
    Olaf Gross
    Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
    Immunity 36:388-400. 2012
    ..Because inflammasomes contribute to the pathology of numerous chronic inflammatory diseases such as gout and diabetes, IL-1α antagonists may be beneficial in the treatment of these disorders...
  39. ncbi Active caspase-1 is a regulator of unconventional protein secretion
    Martin Keller
    Institute of Cell Biology, Department of Biology, ETH Zurich, CH 8093 Zurich, Switzerland
    Cell 132:818-31. 2008
    ..By this mechanism, stress-induced activation of caspase-1 directly links inflammation to cytoprotection, cell survival, and regenerative processes...
  40. ncbi Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival
    Laure Gurcel
    Department Microbiology and Molecular Medicine, University of Geneva, 1 rue Michel Servet, CH 1211 Geneva 4, Switzerland
    Cell 126:1135-45. 2006
    ....
  41. pmc Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages
    Mihai G Netea
    Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, USA
    Blood 113:2324-35. 2009
    ..We conclude that IL-1beta production is differentially regulated in monocytes and macrophages, and this reflects their separate functions in host defense and inflammation...
  42. ncbi Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf
    Amal Amer
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 281:35217-23. 2006
    ..These results reveal that Ipaf restricts Legionella replication through the regulation of phagosome maturation, providing a novel function for NLR proteins in host defense against an intracellular bacterium...
  43. pmc The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity
    Luigi Franchi
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Eur J Immunol 38:2085-9. 2008
    ..These results indicate that alum induces IL-1beta via the Nlrp3 inflammasome but this activity is dispensable for alum-mediated adjuvant activity...
  44. pmc Inflammasome recognition of influenza virus is essential for adaptive immune responses
    Takeshi Ichinohe
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Exp Med 206:79-87. 2009
    ..These results demonstrate that in addition to the TLR pathways, ASC inflammasomes play a central role in adaptive immunity to influenza virus...
  45. pmc Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages
    Toshihiko Suzuki
    Division of Bacterial Pathogenesis, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
    PLoS Pathog 3:e111. 2007
    ..Furthermore, the absence of Ipaf or caspase-1, but not ASC, regulates pyroptosis and the induction of autophagy in Shigella-infected macrophages, providing a novel function for NLR proteins in bacterial-host interactions...
  46. ncbi Phosphorylation of NLRC4 is critical for inflammasome activation
    Yan Qu
    Department of Physiological Chemistry, Genentech Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 490:539-42. 2012
    ..typhimurium infection, so phosphorylation of NLRC4 S533 probably drives conformational changes necessary for NLRC4 inflammasome activity and host innate immunity...
  47. pmc AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
    Teresa Fernandes-Alnemri
    Department of Biochemistry and Molecular Biology, Center for Apoptosis Research, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Nature 458:509-13. 2009
    ..This study identifies AIM2 as an important inflammasome component that senses potentially dangerous cytoplasmic DNA, leading to activation of the ASC pyroptosome and caspase-1...
  48. pmc Immune recognition of Pseudomonas aeruginosa mediated by the IPAF/NLRC4 inflammasome
    Fayyaz S Sutterwala
    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Exp Med 204:3235-45. 2007
    ..This study shows a key role for IPAF and capase-1 in innate immune responses to the pathogen P. aeruginosa, and also demonstrates that virulent ExoU-expressing strains of P. aeruginosa can circumvent this innate immune response...
  49. pmc Mycobacterium tuberculosis prevents inflammasome activation
    Sharon S Master
    Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
    Cell Host Microbe 3:224-32. 2008
    ..Thus, we uncovered a previously masked role for IL-1beta in the control of Mtb and a mycobacterial system that prevents inflammasome and, therefore, IL-1beta activation...
  50. ncbi Emerging inflammasome effector mechanisms
    Mohamed Lamkanfi
    Department of Biochemistry, Ghent University, Ghent, Belgium
    Nat Rev Immunol 11:213-20. 2011
    b>Caspase 1 activation by inflammasome complexes in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) induces the maturation and secretion of the pro-inflammatory cytokines ..
  51. pmc An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans
    Amy G Hise
    Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106, USA
    Cell Host Microbe 5:487-97. 2009
    ..Therefore, in addition to sensing bacterial and viral pathogens, the NLRP3 inflammasome senses fungal pathogens and is critical in host defense against Candida...
  52. ncbi The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme
    J Yuan
    Program of Neurosciences, Harvard Medical School, Boston, Massachusetts 02115
    Cell 75:641-52. 1993
    ..We propose that the CED-3 protein acts as a cysteine protease in the initiation of programmed cell death in C. elegans and that cysteine proteases also function in programmed cell death in mammals...
  53. pmc Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation
    Kristiina Rajamäki
    Wihuri Research Institute, Helsinki, Finland
    PLoS ONE 5:e11765. 2010
    ..As cholesterol crystals are abundant in atherosclerotic lesions, and IL-1beta has been linked to atherogenesis, we explored the possibility that cholesterol crystals promote inflammation by activating the inflammasome pathway...
  54. pmc Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells
    Robin R Craven
    Department of Medicine Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, United States of America
    PLoS ONE 4:e7446. 2009
    ..aureus virulence factor to a specific host signaling pathway. The cellular events linked to inflammasome activity have clear relevance to the disease processes associated with CA-MRSA including tissue necrosis and inflammation...
  55. pmc Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection
    Sarah E Warren
    Department of Immunology, University of Washington, Seattle WA 98195, USA
    J Immunol 180:7558-64. 2008
    ..Cytosolic L. monocytogenes activates caspase 1, resulting in post-translational processing of the cytokines IL-1beta and IL-18 as well as caspase 1-dependent ..
  56. ncbi Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling
    Thirumala Devi Kanneganti
    Department of Pathology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Immunity 26:433-43. 2007
    ..These results provide evidence for cytosolic delivery and sensing of bacterial molecules as a unifying model for caspase-1 activation and position pannexin-1 as a mechanistic link between bacterial stimuli and the cryopyrin inflammasome...
  57. ncbi Substrate specificities of caspase family proteases
    R V Talanian
    BASF Bioresearch Corp, Worcester, Massachusetts 01605, USA
    J Biol Chem 272:9677-82. 1997
    ..The results also suggest the design of optimal peptidic substrates and inhibitors...
  58. pmc Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo
    Katrin D Mayer-Barber
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 184:3326-30. 2010
    ..Together our findings reveal a major role for IL-1beta in host resistance to M. tuberculosis and indicate that during this infection the cytokine can be generated by a mechanism that does not require TLR signaling or caspase-1...
  59. ncbi Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy
    Nicolas Dupont
    Cellular Microbiology and Infectious Pathogeny UMR8161 CNRS, 1 rue du Prof Calmette, F 59021 Lille, France
    Cell Host Microbe 6:137-49. 2009
    ....
  60. ncbi NLRs at the intersection of cell death and immunity
    Jenny P Y Ting
    Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Nat Rev Immunol 8:372-9. 2008
    ....
  61. pmc Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASC
    Stephen B Willingham
    Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Cell Host Microbe 2:147-59. 2007
    ..While similar proteins mediate pathogen-induced cell death in plants, this report identifies cryopyrin as an important host regulator of programmed pathogen-induced necrosis in animals, a process we term pyronecrosis...
  62. pmc NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense
    Luigi Franchi
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Nat Immunol 13:449-56. 2012
    ..Thus, NLRC4-dependent production of IL-1β by intestinal phagocytes represents a specific response that discriminates pathogenic bacteria from commensal bacteria and contributes to host defense in the intestine...
  63. pmc Activation of an NLRP3 inflammasome restricts Mycobacterium kansasii infection
    Chang Chieh Chen
    Green Energy and Environment Research Laboratories, Industrial Technology Research Institute, Chutung, Hsinchu, Taiwan, Republic of China
    PLoS ONE 7:e36292. 2012
    ..Finally, the secreted IL-1β derived from caspase-1 activation was shown to restrict intracellular M. kansasii. These findings demonstrate a biological role for the NLRP3 inflammasome in host defense against M. kansasii...
  64. pmc Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4
    Bo Hu
    Department of Immunobiology, Section of Comparative Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 107:21635-40. 2010
    ..We suggest a model in which the NLRC4 inflammasome is central to colonic inflammation-induced tumor formation through regulation of epithelial cell response to injury...
  65. ncbi Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE
    S Wang
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 92:501-9. 1998
    ..Our data suggest that caspase-11 is a component of ICE complex and is required for the activation of ICE...
  66. ncbi Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase
    M Tewari
    Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA
    Cell 81:801-9. 1995
    ..Furthermore, CrmA blocked cleavage of PARP in cells undergoing apoptosis. We propose that Yama may represent an effector component of the mammalian cell death pathway and suggest that CrmA blocks apoptosis by inhibiting Yama...
  67. pmc Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome
    Christine Juliana
    Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 285:9792-802. 2010
    ..Our results thus elucidate the molecular mechanism for the therapeutic anti-inflammatory activity of parthenolide and identify vinyl sulfones as a new class of potential therapeutics that target the NLRP3 inflammasome...
  68. pmc Asc and Ipaf Inflammasomes direct distinct pathways for caspase-1 activation in response to Legionella pneumophila
    Christopher L Case
    Section of Microbial Pathogenesis, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA
    Infect Immun 77:1981-91. 2009
    ..pneumophila replication in mice. Thus, L. pneumophila-mediated caspase-1 activation involves the coordinate activities of inflammasomes differentially regulated by Ipaf and Asc...
  69. pmc The role of potassium in inflammasome activation by bacteria
    Cecilia S Lindestam Arlehamn
    Division of Immunology, Infection, and Inflammation, University of Glasgow, Glasgow G12 8TA, Scotland, United Kingdom
    J Biol Chem 285:10508-18. 2010
    ..The inhibitory effect of raised extracellular K(+) on NLRC4 activation thus reflects a requirement for a decrease in intracellular K(+) for this inflammasome component as well as that described for NLRP3...
  70. ncbi A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes
    N A Thornberry
    Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065
    Nature 356:768-74. 1992
    ..Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target...
  71. pmc Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms
    Susan L Fink
    Molecular and Cellular Biology Program, Departments of Microbiology and Laboratory Medicine, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 105:4312-7. 2008
    ....
  72. pmc The inflammasomes: mechanisms of activation and function
    Eicke Latz
    University of Massachusetts Medical School, Department of Infectious Diseases and Immunology, 364 Plantation St, Worcester, MA 01605, USA
    Curr Opin Immunol 22:28-33. 2010
    ..Recent work proposes that NLRP3 is activated indirectly by host factors that are generated in response to NLRP3 triggers...
  73. ncbi Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants
    Stephanie C Eisenbarth
    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 453:1122-6. 2008
    ..This is likely to affect how we design effective, but safe, adjuvants in the future...
  74. ncbi Cell death in the host response to infection
    K Labbe
    Department of Microbiology and Immunology, McGill University, Montreal, Canada H3A 2B4
    Cell Death Differ 15:1339-49. 2008
    ..The pathways leading to cell death by infection are discussed with a focus on the role of pattern recognition receptors in the activation of survival and death effectors...
  75. ncbi Human ICE/CED-3 protease nomenclature
    E S Alnemri
    Cell 87:171. 1996
  76. pmc Inflammasomes: too big to miss
    Andrea Stutz
    Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Clin Invest 119:3502-11. 2009
    ..We discuss the current knowledge of the mechanisms leading to the activation of cytoplasmic, multimolecular protein complexes, termed "inflammasomes," which regulate the activity of caspase-1 and the maturation and release of IL-1beta...
  77. pmc Reactive oxygen species-independent activation of the IL-1beta inflammasome in cells from patients with chronic granulomatous disease
    Frank L van de Veerdonk
    Department of Medicine, Radboud University Nijmegen Medical Center and Nijmegen Institute for Infection, Inflammation, and Immunity N4i, 6500 HB Nijmegen, The Netherlands
    Proc Natl Acad Sci U S A 107:3030-3. 2010
    ..The absence of ROS in CGD monocytes may explain the presence of an inflammatory phenotype characterized by granulomas and inflammatory bowel disease occurring in CGD patients...
  78. ncbi Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin
    Eric D Boyden
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 38:240-4. 2006
    ....
  79. pmc Inflammasome sensor Nlrp1b-dependent resistance to anthrax is mediated by caspase-1, IL-1 signaling and neutrophil recruitment
    Mahtab Moayeri
    Laboratory of Bacterial Diseases, Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Pathog 6:e1001222. 2010
    ..These data confirm an inverse relationship between murine macrophage sensitivity to lethal toxin and mouse susceptibility to spore infection, and establish roles for Nlrp1b(S), caspase-1, and IL-1β in countering anthrax infection...
  80. pmc Activation of the Nlrp3 inflammasome by Streptococcus pyogenes requires streptolysin O and NF-kappa B activation but proceeds independently of TLR signaling and P2X7 receptor
    Jurgen Harder
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Immunol 183:5823-9. 2009
    ..pyogenes peritoneal infection. These results indicate that caspase-1 activation in response to S. pyogenes infection requires NF-kappaB and the virulence factor streptolysin O, but proceeds independently of P2X7R and TLR signaling...
  81. pmc Pseudomonas aeruginosa activates caspase 1 through Ipaf
    Edward A Miao
    Institute for Systems Biology, Seattle, WA 98103, USA
    Proc Natl Acad Sci U S A 105:2562-7. 2008
    The innate immune system encodes cytosolic Nod-like receptors (NLRs), several of which activate caspase 1 processing and IL-1beta and IL-18 secretion...
  82. ncbi Superoxide dismutase 1 regulates caspase-1 and endotoxic shock
    Felix Meissner
    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany
    Nat Immunol 9:866-72. 2008
    ..Our findings identify a physiological post-translational mechanism in the control of caspase-1-mediated inflammatory processes...
  83. pmc An NLRP7-containing inflammasome mediates recognition of microbial lipopeptides in human macrophages
    Sonal Khare
    Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Immunity 36:464-76. 2012
    ..Our study therefore increases our currently limited understanding of NLR activation, inflammasome assembly, and maturation of IL-1β and IL-18 in human macrophages...
  84. pmc Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking
    Jianning Ge
    National Institute of Biological Sciences, Beijing 102206, China
    Proc Natl Acad Sci U S A 109:6193-8. 2012
    ..Our data together suggest a possible link, mediated by the function of SdhA, between LCV trafficking/maturation and suppression of host innate immune detection...
  85. ncbi Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome
    Katherine Labbe
    Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3G 0B1, Canada
    Immunity 35:897-907. 2011
    ..Our results describe a role for the cIAPs in innate immunity and further demonstrate the evolutionary conservation between cell death and inflammation mechanisms...
  86. ncbi Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1
    Jean Marie Bruey
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell 129:45-56. 2007
    ..The findings reveal an interaction of host defense and apoptosis machinery...
  87. pmc Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase
    Najwane Saïd-Sadier
    Health Sciences Research Institute and School of Natural Sciences, University of California Merced, Merced, California, USA
    PLoS ONE 5:e10008. 2010
    ....
  88. pmc Inflammasome-dependent caspase-1 activation in cervical epithelial cells stimulates growth of the intracellular pathogen Chlamydia trachomatis
    Ali A Abdul-Sater
    Health Sciences Research Institute and School of Natural Sciences, University of California, Merced, California 95343, USA
    J Biol Chem 284:26789-96. 2009
    ..Here we show that, in cervical epithelial cells, caspase-1 activation is required for optimal growth of the intracellular chlamydiae...
  89. pmc NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses
    Denis Gris
    Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA
    J Immunol 185:974-81. 2010
    ..Thus, NLRP3 plays a critical role in the induction of the EAE, likely through effects on capase-1-dependent cytokines which then influence Th1 and Th17...
  90. pmc A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide
    Li Chung Hsu
    Departments of Pharmacology and Pathology, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:7803-8. 2008
    ..Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion...
  91. pmc Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection
    Barbel Raupach
    Department of Cellular Microbiology, Max Planck Institut für Infektionsbiologie, Schumannstrasse 21 22, 10117 Berlin, Germany
    Infect Immun 74:4922-6. 2006
    ..Thus, we show that Casp-1 is essential for host innate immune defense against S. enterica serovar Typhimurium and that Casp-1 substrates are required at distinct times and anatomical sites...
  92. ncbi Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1 beta and resistant to endotoxic shock
    P Li
    BASF Bioresearch Corporation, Worcester, Massachusetts 01605 4314
    Cell 80:401-11. 1995
    ..ICE therefore plays a dominant role in the generation of mature IL-1 beta, a previously unsuspected role in production of IL-1 alpha, but has no autonomous function in apoptosis...
  93. pmc Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease
    Felix Meissner
    Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Berlin, Germany
    Blood 116:1570-3. 2010
    ..Our results identify phagocyte oxidase defective monocytes as a source of elevated IL-1 and provide a potential therapeutic option to ameliorate inflammatory conditions associated with CGD...
  94. pmc The AIM2 inflammasome is critical for innate immunity to Francisella tularensis
    Teresa Fernandes-Alnemri
    Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    Nat Immunol 11:385-93. 2010
    ..tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens...
  95. pmc Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella
    Petr Broz
    Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA, USA
    J Exp Med 207:1745-55. 2010
    ..typhimurium, mice lacking both NLRs were markedly more susceptible to infection. These results reveal unexpected redundancy among NLRs in host defense against intracellular pathogens in vivo...
  96. pmc Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1
    Erin McElvania TeKippe
    Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS ONE 5:e12320. 2010
    ..These data demonstrate that PYCARD exerts a novel inflammasome-independent role during chronic Mtb infection by containing the bacteria in granulomas...
  97. ncbi An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome
    Tilmann Burckstummer
    Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
    Nat Immunol 10:266-72. 2009
    ..Reconstitution of unresponsive HEK293 cells with AIM2, ASC, caspase-1 and interleukin 1beta showed that AIM2 was sufficient for inflammasome activation. Our data suggest that AIM2 is a cytoplasmic DNA sensor for the inflammasome...
  98. pmc Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation
    Luigi Franchi
    University of Michigan Medical School, Department of Pathology and Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA
    J Immunol 183:792-6. 2009
    ..These results provide a mechanism by which danger signals and particulate matter mediate inflammation via the Nlrp3 inflammasome in the absence of microbial infection...
  99. ncbi The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes
    Laurence Feldmeyer
    Institute of Cell Biology, Department of Biology, ETH Zurich, Zurich, Switzerland
    Curr Biol 17:1140-5. 2007
    ..This supports the concept that keratinocytes are important immuno-competent cells under physiological and pathological conditions [5]...
  100. pmc Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases
    Marina Tiemi Shio
    Department of Medicine, Microbiology and Immunology, Centre for the Study of Host Resistance, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
    PLoS Pathog 5:e1000559. 2009
    ..These findings not only identify one way by which the immune system is alerted to malarial infection but also are one of the first to suggest a role for tyrosine kinase signaling pathways in regulation of the NLRP3 inflammasome...
  101. ncbi Molecular cloning of the interleukin-1 beta converting enzyme
    D P Cerretti
    Immunex Corporation, Seattle, WA 98101
    Science 256:97-100. 1992
    ..Sequence analysis indicated that the enzyme itself may undergo proteolytic processing. The gene encoding the protease was mapped to chromosomal band 11q23, a site frequently involved in rearrangement in human cancers...

Research Grants70

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  2. Pulmonary Defenses Against Intracellular Infection
    Shawn J Skerrett; Fiscal Year: 2013
    ....
  3. Sterile Hepatic Inflammation
    Wajahat Zafar Mehal; Fiscal Year: 2012
    ..The knowledge gained from this project will therefore directly result in designing rational therapies for these conditions. ..
  4. Immunobiology of Acute Environmental Asthma
    David B Peden; Fiscal Year: 2013
    ..The inflammasome complex is required for procaspase 1 processing to mature caspase 1. In turn, caspase-1 is required for the processing of pro-IL-1 and pro-IL-18 to their mature forms...
  5. TARGETING FLIP FOR PROSTATE CANCER PREVENTION
    Addanki P Kumar; Fiscal Year: 2012
    ....
  6. Mechanistic study of the host defense functions of IL-32 in tuberculosis
    Edward D Chan; Fiscal Year: 2013
    ..Additionally, enhancing the bioactivity of IL-32 should increase induction of PCD and MTB killing. ..
  7. Molecular mechanisms of pathogen recognition by the Nod-like receptor NLRC4
    Fayyaz S Sutterwala; Fiscal Year: 2012
    ..iii) Determining if NLRC4 recognizes host plasma membrane components following their disruption by bacterial T3SS. ..
  8. ROS, Inflammation, and Cardioprotection in Type 2 Diabetes
    Rakesh C Kukreja; Fiscal Year: 2013
    ..Overall, the proposed studies will pave the way to a potentially novel pharmacotherapy against inflammation and cardiac injuries resulting from T2D conditions. ..
  9. Role of Interleukin-1 in mediating epithelial-dendritic cell crosstalk in the lun
    BART N contact LAMBRECHT; Fiscal Year: 2010
    ..This project will help unravel how individuals become allergic when exposed to house dust mite allergen. ..
  10. Regulation of caspase-1 by Sod2 in the heart
    Kumuda C Das; Fiscal Year: 2010
    ..The outcome of these studies may help in the therapeutic use of MnSOD or substances that induce MnSOD in the protection of myocardial injury in heart failure, endothelial dysfunction or other cardiovascular diseases. ..
  11. Neutrophil Accumulation in Bacterial Pneumonia
    Samithamby Jeyaseelan; Fiscal Year: 2013
    ....
  12. Inflammasome Activation in Complex Regional Pain Syndrome
    Wade S Kingery; Fiscal Year: 2013
    ....
  13. Inflammasome activation by a respiratory virus
    Christopher M Wiethoff; Fiscal Year: 2010
    ....
  14. Gender-Specific Role of Aim2 in Inflammation and Autoimmunity
    Divaker Choubey; Fiscal Year: 2011
    ..Moreover, our studies will help in the rational design of new therapies and treatments for chronic inflammatory diseases, including systemic lupus erythematosus (SLE). ..
  15. ERK Signaling in Inflammatory Bone Loss
    Francis Young In Lee; Fiscal Year: 2013
    ..Overall impact is high in that we expect to unravel novel anti-osteoclastogenic mechanisms and therapeutic promise of rhCRG in the context of inflammatory osteolysis. ..
  16. Cryopyrin/NLRP3 Signaling in Inflammation and Innate Immunity
    Gabriel Nunez; Fiscal Year: 2013
    ..These studies may lead to better understanding of mechanisms that control host defense against human pathogens and the pathogenesis of inflammatory disease. ..
  17. Inflammasomes in pathogenesis of mesothelioma
    Arti Shukla; Fiscal Year: 2013
    ..The goal of these studies will be to demonstrate the role of inflammasomes in MM development and may help in designing future therapeutic strategies for patients. ..
  18. Detection &Use of Novel Therapeutics to Stimulate NLRP3 Activity in the Elderly
    HEATHER WINONA STOUT-DELGADO; Fiscal Year: 2013
    ....
  19. Caspase-1 and Inflammasome Activation in Traumahemorrhagic Shock
    Melanie J Scott; Fiscal Year: 2013
    ..Understanding these novel pathways of inflammatory activation and function in individual cell types and organs may help us find new ways to treat and prevent MOF in trauma patients in the future. ..
  20. MECHANISMS OF ACTIVATION OF ICE-LIKE CYSTEINE PROTEASES
    Emad S Alnemri; Fiscal Year: 2012
    ..The results of this research will help in the design and discovery of effective therapeutics to treat inflammation associated with aging, auto-inflammatory disease and chronic inflammatory diseases. ..
  21. IL-1 beta Signaling in Diabetic Retinopathy
    Susanne Mohr; Fiscal Year: 2010
    ..These studies will clarify if the caspase-1/interleukin-1beta signaling pathway is essential for the development of diabetes-induced retinal pathology. ..
  22. How can caspases control intracellular pulmonary pathogens
    Amal O Amer; Fiscal Year: 2010
    ..This project will help understand how bacteria establish infection, and how the host cell responds to this intracellular pathogen. Therefore, our aims will lead to better management of intracellular infections. ..
  23. Nlrp3 inflammasome signaling in immune responses to Candida albicans
    Fayyaz S Sutterwala; Fiscal Year: 2013
    ..In addition the information gained from the proposed studies will also shed light on the pathogenesis of other fungal organisms. ..
  24. Tim3 and Mycobacterium tuberculosis
    Samuel M Behar; Fiscal Year: 2013
    ..Does IL-1 and its downstream mediators activate human MX to kill Mtb? 7 Aim 3. How does the Tim3/Gal9 interaction modulate immunity to tuberculosis in vivo? ..
  25. Innate Immune Activation in Malaria
    Douglas T Golenbock; Fiscal Year: 2013
    ..Gallego spends in South America will increase, with the ultimate goal of exporting cutting edge technology and expertise to the scientific community in Colombia. ..
  26. Development of inlammasome inhibitors to be used as anti-inflammatory agents
    Shyam Biswal; Fiscal Year: 2013
    ..Successful completion of the proposed study will yield novel compounds that inhibit the inflammasome in cell-based systems. ..
  27. Effects of a chlamydial ATP-consuming enzyme on the inflammasome
    MARIA LUISA AVILA; Fiscal Year: 2010
    ..Investigate the ability of cNdk to modulate the activity of the Nalp3/Cryopyrin inflammasome in cells stimulated with microbial products. ..
  28. Cysteine Proteases in Apoptosis
    Emad S Alnemri; Fiscal Year: 2012
    ..The results of this research will help in the design and discovery of effective therapeutics to treat autoinflammatory diseases. ..
  29. Inflammasome Danger Signaling:A Novel Target to Prevent Debris Induced Osteolysis
    Nadim James Hallab; Fiscal Year: 2013
    ..e. from initial lysosomal destabilization and NADPH oxidase induction of ROS, to NALP3-ASC oligomerization, and Caspase 1 conversion of pro-IL-1 to IL-1...
  30. Role of the inflammasome in hepatitis C virus pathogenesis
    Gulam Waris; Fiscal Year: 2012
    ..In addition, it is expected that the results will fundamentally advance the fields of liver inflammation and lipid metabolism mediated by HCV-infection. ..
  31. Impact of CR on inflammasome driven immune-metabolic interactions.
    Vishwa Deep Dixit; Fiscal Year: 2013
    ....
  32. 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. ..
  33. Inflammasome Response to Bacterial Infection
    Edward A Miao; Fiscal Year: 2013
    ..Our results will be instructive for designing live attenuated vaccines as well as vaccine adjuvants. The general mechanisms revealed by these studies will also facilitate the understanding of inflammatory disease. ..
  34. Innate Immune Sensing of Bacterial Sugars
    David M Underhill; Fiscal Year: 2013
    ..In aim three well will explor how the Gram-positive peptidoglycan recycling system can be manipulated to influence signaling by this pathway in immune cells and alter microbial pathogenesis. ..
  35. Macrophage Inflammasome Regulation
    MARK DAMIAN WEWERS; Fiscal Year: 2013
    ..If confirmed, these novel hypotheses will change our concepts about IL-1[unreadable] regulation and provide new treatment options for inflammatory lung disorders. ..
  36. The Role of Inflammasomes in Mucosal Immunity to Intestinal Bacterial Pathogens
    Gabriel Nunez; Fiscal Year: 2013
    ..coli, two enteric bacterial pathogens. These studies may lead to better understanding of mechanisms that control host defense against human pathogens and the pathogenesis of inflammatory disease in the intestine. ..
  37. Innate Immunity and Pathogen mediated Acceleration in Vascular Inflammation
    Shuang Chen; Fiscal Year: 2013
    ..These studies thus may provide potential novel molecular targets to prevent infection-mediated disease progression. ..
  38. RIP2 caspase-1 signaling in macrophages
    MARK DAMIAN WEWERS; Fiscal Year: 2013
    ..abstract_text> ..
  39. DNA sensors and associated signaling pathways in the innate immune response
    Katherine A Fitzgerald; Fiscal Year: 2013
    ..This project will increase our understanding of how the innate immune system senses pathogens, leading to novel therapeutic targets. ..
  40. Modulation of Inflammasome Activation by Yersinia
    Igor E Brodsky; Fiscal Year: 2013
    ..Third, we will test te hypothesis that inflammasome activation in vivo controls Yersinia infection via production of caspase-1 dependent cytokines that induce activation of specific immune cell subsets that promote bacterial clearance. ..
  41. Role of Mast cells in NLRP3-mediated Skin Inflammation
    Gabriel Nunez; Fiscal Year: 2013
    ..We will use genetic and functional approaches to understand the regulation and activation of the NLRP3 inflammasome in MCs and the role of MCs in the pathogenesis of autoinflammatory disease caused by NLRP3 mutations. ..
  42. 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. ..
  43. Manipulation of inflammasomes and NF-kB signaling in human myeloid cells by Myxom
    Grant McFadden; Fiscal Year: 2013
    ..regulate the inflammasome and NF-?B signaling pathways and test these M013 constructs in an in vivo caspase 1- dependent rat transplant vascular disease model: We will generate M013 mutants that selectively inhibit either ..
  44. NOD-Like Receptor Signaling is Critical to Secondhand Smoke-Induced Immunity and
    Sanjay Batra; Fiscal Year: 2013
    ..Unique resources include NALP12 knockout mice and human alveolar macrophages. The R15 mechanism will help to train undergraduates including minority students in the field of emerging and devastating lung diseases such as COPD/Emphysema. ..
  45. Pulmonary Pathogen-Recognition Pathways in Melioidosis
    TIMOTHY EOIN WEST; Fiscal Year: 2013
    ..The findings may also be applicable to other respiratory infections - leading causes of death and disability worldwide that disproportionately impact the poor. ..
  46. NLRP1 activation induces deletion of hematopoietic progenitor cells
    BEN ADAM CROKER; Fiscal Year: 2013
    ..C. characterise the role of NLRP1 in hematopoietic stem and progenitor cells during hematopoietic stress induced by infection and chemotherapy, to understand beneficial and pathological roles for NLRP1 activation ..
  47. PATHOGENESIS OF FEVER IN HUMANS
    CHARLES ANTHONY DINARELLO; Fiscal Year: 2013
    ..The project seeks to understand how inflammation caused by cytokines is controlled. This information will result in a better understanding of disease severity and possibly new anti-inflammatory therapies. ..
  48. ??PK mediated melanoma stem cell oncolysis through non-redundant programmed cell
    ARIC G COLUNGA; Fiscal Year: 2011
    ..The working hypothesis is that PCD induction by delta PK is augmented by autophagy and pyroptosis and delta PK infects and kills melanoma stem cells through one or more of these pathways. ..
  49. Cytosolic sensing of intracellular Brucella infection
    Renee M Tsolis; Fiscal Year: 2013
    ..abstract_text> ..
  50. Role of PISA;a PYHIN Family Member in Intracellular DNA Recognition
    Eicke Latz; Fiscal Year: 2013
    ..Elucidation of molecular details of PISA activation could lead to novel strategies of pharmacological interference for diseases based on intracellular DNA recognition. ..
  51. Innate immune responses in keratinocytes during viral skin infections
    Liselotte E Jensen; Fiscal Year: 2013
    ..The gained knowledge may explain mechanisms of action of therapeutic agents and will inform future drug development, including IL-36? as a novel wound healing agent. ..
  52. Mechanisms of CD36 Signal Transduction - Resubmission - 1
    Kathryn J Moore; Fiscal Year: 2013
    ....
  53. Role of caspases in Legionella pneumophila pulmonary infection
    Amal O Amer; Fiscal Year: 2013
    ..This will represent a novel approach to the treatment and management of infection and inflammation in the lung. ..
  54. Repression of inflammasome by Francisella tularensis
    Meenakshi Malik; Fiscal Year: 2013
    ..This proposal is a step ahead in understanding the immunopathogenesis of tularemia. ..
  55. The Role of Caspases in Warm and Cold Ischemia
    ALKESH HARIHAR JANI; Fiscal Year: 2010
    ..Reduced MHC expression is associated with decreased kidney graft immunogenicity and has important implications for the deleterious effect of DGF on both short and long-term allograft function. ..
  56. Role of PSTPIP1 in a Mouse Model of PAPA Syndrome
    Donghai Wang; Fiscal Year: 2012
    ..It is thought that mutant PSTPIP1 multimerizes spontaneously, subsequently binds PYRIN, and activates caspase 1 via the adapter ASC...
  57. Annexin A2 and Protein p11 in Endotoxemia and Sepsis
    KATHERINE AMBERSON HAJJAR; Fiscal Year: 2013
    ....
  58. Regulation of Innate Immunity by Pyrin Proteins
    Jonathan A Harton; Fiscal Year: 2012
    ..3) Establish the in vivo role of POP2 in modulating inflammatory innate immune responses. ..
  59. Mechanisms of Caspase-1 Mediated Schwannoma Regression
    GARY JAY BRENNER; Fiscal Year: 2013
    ....
  60. Inflammasomes and the mechanism of thymic demise in aging
    Vishwa Deep Dixit; Fiscal Year: 2013
    ..The overall goal of this project is to identify basic mechanism of thymic demise that are amenable for future clinical intervention to delay or even reverse thymic involution in middle-aged or elderly people. ..
  61. Inflammasome activation by cholesterol crystals
    Eicke Latz; Fiscal Year: 2013
    ..abstract_text> ..
  62. Mechanisms of Inflammasome Inhibition by Salmonella
    Igor E Brodsky; Fiscal Year: 2013
    ..These studies will provide novel insight into a critical aspect of Salmonella-host interactions, and are likely to provide novel therapeutic targets. ..
  63. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2007
    ..P.I. Dr. Robert Miller). ..
  64. CRITICAL ROLE OF THE ASC/CASPASE-1 PATHWAY IN TICK-BORNE RICKETTSIOSES
    JOAO PEDRA; Fiscal Year: 2009
    ..To accomplish these goals, Dr. Pedra will have free access to the modern facilities present at Yale University and will make use of the most current techniques available in immunobiology, microbial pathogenesis and proteomics. ..
  65. The role of macrophages and natural killer cells in cisplatin-induced acute renal
    Lawrence Lu; Fiscal Year: 2007
    ..Better understanding of the underlying inflammatory mechanisms may lead to improved preventative and treatment strategies. [unreadable] [unreadable] [unreadable]..
  66. Innate immune resistance to intracellular bacterial pathogens
    RUSSELL VANCE; Fiscal Year: 2007
    ..Such knowledge should contribute to rational approaches to designing novel antibacterial therapies. [unreadable] [unreadable] [unreadable]..
  67. Viral PYRIN-only proteins as suppressors of the host immune response
    Christian Stehlik; Fiscal Year: 2007
    ..The here proposed work extends our long-term goal to define pathogen-host interactions and their effect on the immune response. [unreadable] [unreadable]..
  68. REGULATION OF MACROPHAGE INTERLEUKIN-1 BETA PRODUCTION
    MARK WEWERS; Fiscal Year: 2006
    ..We hypothesize that MAIL, a novel protein homologue of I-kBalpha that we discovered by yeast two-hybrid screening negatively regulates prolL-1beta processing and release. ..
  69. The Human Colorectal Instabilitome
    Stephen Meltzer; Fiscal Year: 2007
    ..genes on protein expression and signal transduction, including phosphorylated and total SMAD2, total SMAD4, caspase 1, and TTK; 2.b...
  70. Interleukin-18 and Intestinal Barrier Function Following Alcohol and Burn Injury
    Mashkoor Choudhry; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..