GARY STEVEN FIRESTEIN

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc DNA methylome signature in rheumatoid arthritis
    Kazuhisa Nakano
    Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA
    Ann Rheum Dis 72:110-7. 2013
  2. pmc Regulation of inflammatory arthritis by the upstream kinase mitogen activated protein kinase kinase 7 in the c-Jun N-terminal kinase pathway
    Sang Il Lee
    Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, CA, USA
    Arthritis Res Ther 14:R38. 2012
  3. pmc Regulation of peripheral inflammation by the central nervous system
    Jean Marc Waldburger
    Division of Rheumatology, Geneva University Hospital, Geneva, Switzerland
    Curr Rheumatol Rep 12:370-8. 2010
  4. pmc PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53
    Xin You
    Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093, USA
    Arthritis Res Ther 8:R157. 2006
  5. pmc Garden of therapeutic delights: new targets in rheumatic diseases
    Jean M Waldburger
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, Mail Code 0656, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Arthritis Res Ther 11:206. 2009
  6. pmc Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes
    Deepa R Hammaker
    Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, Gilman Dr, La Jolla, CA 92093, USA
    Arthritis Res Ther 9:R57. 2007
  7. pmc p53 tumor suppressor gene mutations in fibroblast-like synoviocytes from erosion synovium and non-erosion synovium in rheumatoid arthritis
    Yuji Yamanishi
    Department of Rheumatology, Hiroshima City Hospital, Hiroshima, Japan
    Arthritis Res Ther 7:R12-8. 2005
  8. pmc Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature
    D M Gerlag
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA
    Arthritis Res 3:357-61. 2001
  9. ncbi request reprint Common mechanisms in immune-mediated inflammatory disease
    Gary S Firestein
    Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California at San Diego, San Diego, California, USA
    J Rheumatol Suppl 73:8-13; discussion 29-30. 2005
  10. ncbi request reprint Immunologic mechanisms in the pathogenesis of rheumatoid arthritis
    Gary S Firestein
    Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive BSB, Rm 5098, La Jolla, CA 92093, USA
    J Clin Rheumatol 11:S39-44. 2005

Detail Information

Publications78

  1. pmc DNA methylome signature in rheumatoid arthritis
    Kazuhisa Nakano
    Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA
    Ann Rheum Dis 72:110-7. 2013
    ..Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed...
  2. pmc Regulation of inflammatory arthritis by the upstream kinase mitogen activated protein kinase kinase 7 in the c-Jun N-terminal kinase pathway
    Sang Il Lee
    Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, CA, USA
    Arthritis Res Ther 14:R38. 2012
    ..Therefore, we evaluated whether targeting MKK7 using anti-sense oligonucleotides (ASO) would decrease JNK activation and severity in K/BxN serum transfer arthritis...
  3. pmc Regulation of peripheral inflammation by the central nervous system
    Jean Marc Waldburger
    Division of Rheumatology, Geneva University Hospital, Geneva, Switzerland
    Curr Rheumatol Rep 12:370-8. 2010
    ..Some of the neurotransmitters and neuroreceptors involved have been identified in preclinical models and represent novel targets for the treatment of rheumatic diseases...
  4. pmc PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53
    Xin You
    Division of Rheumatology, Allergy and Immunology, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093, USA
    Arthritis Res Ther 8:R157. 2006
    ..Therefore, approaches to gene therapy that involve increasing PUMA expression could be an effective inducer of synoviocyte cell death in rheumatoid arthritis regardless of the p53 status in the synovium...
  5. pmc Garden of therapeutic delights: new targets in rheumatic diseases
    Jean M Waldburger
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, Mail Code 0656, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Arthritis Res Ther 11:206. 2009
    ..The abundance of potential targets suggests that new and creative ways of evaluating safety and efficacy are needed...
  6. pmc Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes
    Deepa R Hammaker
    Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, Gilman Dr, La Jolla, CA 92093, USA
    Arthritis Res Ther 9:R57. 2007
    ..In contrast to other cell lineages, MEKK1, MEKK2, and MEKK3 did not contribute to JNK phosphorylation in FLSs. The data identify TAK1 as a pivotal upstream kinase and potential therapeutic target to modulate synoviocyte activation in RA...
  7. pmc p53 tumor suppressor gene mutations in fibroblast-like synoviocytes from erosion synovium and non-erosion synovium in rheumatoid arthritis
    Yuji Yamanishi
    Department of Rheumatology, Hiroshima City Hospital, Hiroshima, Japan
    Arthritis Res Ther 7:R12-8. 2005
    ..The determining factor for invasiveness might be proximity to bone or cartilage rather than the presence of a p53 mutation...
  8. pmc Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature
    D M Gerlag
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA
    Arthritis Res 3:357-61. 2001
    ..Targeted apoptosis of synovial neovasculature can induce apoptosis and suppress clinical arthritis. This form of therapy has potential utility in the treatment of inflammatory arthritis...
  9. ncbi request reprint Common mechanisms in immune-mediated inflammatory disease
    Gary S Firestein
    Division of Rheumatology, Allergy, and Immunology, Department of Medicine, University of California at San Diego, San Diego, California, USA
    J Rheumatol Suppl 73:8-13; discussion 29-30. 2005
    ..Understanding the autoimmune and inflammatory pathways implicated in disease has led to targeted drug development and improved clinical outcomes...
  10. ncbi request reprint Immunologic mechanisms in the pathogenesis of rheumatoid arthritis
    Gary S Firestein
    Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive BSB, Rm 5098, La Jolla, CA 92093, USA
    J Clin Rheumatol 11:S39-44. 2005
    ..Although currently approved BRMs still have limitations, choosing an appropriate target, possibly early rather than late in the immune response, might result in new and improved therapies for RA...
  11. pmc Pathogenesis of rheumatoid arthritis: how early is early?
    Gary S Firestein
    Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, California, USA
    Arthritis Res Ther 7:157-9. 2005
    ..Evaluation of the cytokine profile at the earliest time points after onset of symptoms could identify novel targets that prevent progression to chronic arthritis...
  12. pmc Mitogen activated protein kinase inhibitors: where are we now and where are we going?
    S E Sweeney
    University of California San Diego School of Medicine, Mail Code 0656, Division of Rheumatology, Allergy and Immunology, 9500 Gilman Drive, La Jolla, CA 92093 0656, USA
    Ann Rheum Dis 65:iii83-8. 2006
    ..These approaches might permit effective use of MAP kinase inhibitors for the treatment of rheumatic and immune-mediated diseases...
  13. ncbi request reprint Biomedicine. Every joint has a silver lining
    Gary S Firestein
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, MC 0656, La Jolla, CA 92093 0656, USA
    Science 315:952-3. 2007
  14. pmc The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis
    Gary S Firestein
    Division of Rheumatology, Allergy, and Immunology and Clinical Investigation Institute, University of California San Diego School of Medicine, 9500 Gilman Drive, San Diego, CA 92093 0656, USA
    J Clin Invest 114:471-4. 2004
    ..Hence, effective therapeutic interventions can target either unique etiologic pathways related to adaptive immune responses or shared terminal mechanisms...
  15. ncbi request reprint How important are T cells in chronic rheumatoid synovitis?: II. T cell-independent mechanisms from beginning to end
    Gary S Firestein
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0656, USA
    Arthritis Rheum 46:298-308. 2002
  16. ncbi request reprint Evolving concepts of rheumatoid arthritis
    Gary S Firestein
    Division of Rheumatology, Allergy and Immunology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0656, USA
    Nature 423:356-61. 2003
    ..Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis...
  17. pmc Regulation of peripheral inflammation by spinal p38 MAP kinase in rats
    David L Boyle
    Division of Rheumatology, Allergy, and Immunology, University of California San Diego School of Medicine, La Jolla, California, United States of America
    PLoS Med 3:e338. 2006
    ..We therefore determined whether these pathways also regulate peripheral inflammation in rat adjuvant arthritis, which is a model of rheumatoid arthritis...
  18. ncbi request reprint Regulation of JNK by MKK-7 in fibroblast-like synoviocytes
    Tomoyuki Inoue
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0656, USA
    Arthritis Rheum 54:2127-35. 2006
    ..However, the functional hierarchy of MKK-4 and MKK-7 in FLS has not been determined. We determined the relative contributions of these MKKs by evaluating the effect of MKK-4 and MKK-7 gene knockdown in cultured FLS...
  19. pmc Mitogen-activated protein kinase kinase 3 is a pivotal pathway regulating p38 activation in inflammatory arthritis
    Tomoyuki Inoue
    Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0656, USA
    Proc Natl Acad Sci U S A 103:5484-9. 2006
    ..Therefore, selective MKK3 deficiency can suppress inflammatory arthritis and cytokine production while Toll-like receptor 4-mediated host defense remains intact...
  20. ncbi request reprint Regulation of c-Jun phosphorylation by the I kappa B kinase-epsilon complex in fibroblast-like synoviocytes
    Susan E Sweeney
    Division of Rheumatology, Allergy, and Immunology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
    J Immunol 174:6424-30. 2005
    ..These data suggest a novel role for the IKKepsilon complex in synovial inflammation, extracellular matrix destruction, and activation of the viral program and innate immune response in RA...
  21. ncbi request reprint Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinase kinases in rheumatoid arthritis
    Deepa R Hammaker
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA
    J Immunol 172:1612-8. 2004
    ..These data indicate that MEKK2 is a potent activator of the JNK pathway in FLS and that signal complexes including MEKK2, MKK4, MKK7, and/or JNK are potential therapeutic targets in RA...
  22. ncbi request reprint Wnt1 inducible signaling pathway protein-3 regulation and microsatellite structure in arthritis
    Hyeonjoo Cheon
    Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine, La Jolla, California 92093 0656, USA
    J Rheumatol 31:2106-14. 2004
    ..To investigate the contribution of WISP3 to synovial inflammation, we evaluated its expression and regulation in arthritis...
  23. doi request reprint Acetylcholine regulation of synoviocyte cytokine expression by the alpha7 nicotinic receptor
    Jean Marc Waldburger
    University of California, San Diego, La Jolla, CA, USA
    Arthritis Rheum 58:3439-49. 2008
    ..To test this possibility, we evaluated the expression of alpha7R and its potential role as a target in rheumatoid arthritis (RA)...
  24. pmc Measurement of inflammatory biomarkers in synovial tissue extracts by enzyme-linked immunosorbent assay
    Sanna Rosengren
    Center for Innovative Therapy, Division of Rheumatology, Allergy, and Immunology, University of California San Diego School of Medicine, La Jolla, California, USA
    Clin Diagn Lab Immunol 10:1002-10. 2003
    ..These methods allow monitoring of biomarker protein levels in synovial tissue and could potentially be applied to early-phase clinical trials to provide a preliminary estimate of drug efficacy...
  25. ncbi request reprint Regulation of p38 MAPK by MAPK kinases 3 and 6 in fibroblast-like synoviocytes
    Tomoyuki Inoue
    Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, School of Medicine, La Jolla, CA 92093 0656, USA
    J Immunol 174:4301-6. 2005
    ..These data demonstrate that MKK3 and MKK6 make individual contributions to p38 activation in FLS after cytokine stimulation, but that both must be blocked for maximum inhibition...
  26. ncbi request reprint IL-6 and matrix metalloproteinase-1 are regulated by the cyclin-dependent kinase inhibitor p21 in synovial fibroblasts
    Harris Perlman
    Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA
    J Immunol 170:838-45. 2003
    ..These data suggest that alterations in p21 expression may activate AP-1 leading to enhanced proinflammatory cytokine and MMP production and development of autoimmune disease...
  27. ncbi request reprint Expression of the MAPK kinases MKK-4 and MKK-7 in rheumatoid arthritis and their role as key regulators of JNK
    Monisha Sundarrajan
    University of California, San Diego, School of Medicine, La Jolla, 92093, USA
    Arthritis Rheum 48:2450-60. 2003
    ..We therefore evaluated the interactions between the various MAP kinase components and determined their subcellular localization...
  28. pmc Expression and activation of mitogen-activated protein kinase kinases-3 and -6 in rheumatoid arthritis
    Martine Chabaud-Riou
    Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine, La Jolla, California 92093, USA
    Am J Pathol 164:177-84. 2004
    ..By forming a complex with p38 in synovial tissue and FLS, these kinases can potentially be targeted to regulate the production of proinflammatory cytokine production in inflamed synovium...
  29. pmc Gadd45beta deficiency in rheumatoid arthritis: enhanced synovitis through JNK signaling
    Camilla I Svensson
    University of California San Diego School of Medicine, La Jolla, CA 92093, USA
    Arthritis Rheum 60:3229-40. 2009
    ..This study was carried out to evaluate whether low Gadd45beta expression in RA enhances JNK activation and overproduction of MMPs in RA, and whether Gadd45beta deficiency increases arthritis severity in passive K/BxN murine arthritis...
  30. ncbi request reprint Expression and regulation of aggrecanase in arthritis: the role of TGF-beta
    Yuji Yamanishi
    Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA
    J Immunol 168:1405-12. 2002
    ..In contrast, aggrecanase-2 protein may be regulated by a post-translational mechanism in OA and RA ST. Synovial and FLS production of aggrecanase can contribute to cartilage degradation in RA and OA...
  31. ncbi request reprint Retinoblastoma suppression of matrix metalloproteinase 1, but not interleukin-6, through a p38-dependent pathway in rheumatoid arthritis synovial fibroblasts
    Kathleen Bradley
    Saint Louis University, School of Medicine, St Louis, Missouri 63104, USA
    Arthritis Rheum 50:78-87. 2004
    ..Therefore, we sought to determine if the tumor suppressor gene product retinoblastoma (Rb), a negative regulator of cell cycle activity, inhibits IL-6, MMP-1, and p38 in RA synovial fibroblasts...
  32. pmc Kinetic analysis of synovial signalling and gene expression in animal models of arthritis
    Akihisa Fukushima
    Division of Rheumatology, Allergy and Immunology, University of California, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0656, USA
    Ann Rheum Dis 69:918-23. 2010
    ..Animal models of arthritis are frequently used to evaluate novel therapeutic agents. However, their ability to predict responses in humans is variable...
  33. ncbi request reprint Antiviral gene expression in rheumatoid arthritis: role of IKKepsilon and interferon regulatory factor 3
    Susan E Sweeney
    University of California San Diego, School of Medicine, La Jolla, CA 92093, USA
    Arthritis Rheum 56:743-52. 2007
    ..This study was designed to investigate the role of the IKK-related kinase IKKepsilon and IFN regulatory factor 3 (IRF-3) in the activation of antiviral genes in rheumatoid arthritis (RA)...
  34. ncbi request reprint A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes
    Hoon Suk Cha
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA
    J Pharmacol Exp Ther 317:571-8. 2006
    ..These data demonstrate that Syk activation plays an essential role in TNFalpha-induced cytokine and matrix metalloproteinase production in RA FLS, especially by suppressing activation of the JNK pathway...
  35. ncbi request reprint Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant-induced arthritis
    David L Boyle
    Division of Rheumatology, Allergy and Immunology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
    Arthritis Rheum 46:3076-82. 2002
    ..To examine the effect of spinal cord adenosine (Ado) receptor stimulation on rat adjuvant-induced arthritis (AIA)...
  36. pmc Innate immunity as a hired gun: but is it rheumatoid arthritis?
    Maripat Corr
    Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, La Jolla, CA 92093, USA
    J Exp Med 195:F33-5. 2002
  37. ncbi request reprint Joint damage and inflammation in c-Jun N-terminal kinase 2 knockout mice with passive murine collagen-induced arthritis
    Zuoning Han
    University of California San Diego School of Medicine, La Jolla 92093, USA
    Arthritis Rheum 46:818-23. 2002
    ..The present study was undertaken to investigate whether selective loss of JNK-2 function decreases joint destruction in JNK-2 knockout mice, in order to determine the role of this isoform in inflammatory arthritis...
  38. ncbi request reprint Primer: signal transduction in rheumatic disease--a clinician's guide
    Susan E Sweeney
    Division of Rheumatology, Allergy and Immunology, University of California San Diego, Department of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0656, USA
    Nat Clin Pract Rheumatol 3:651-60. 2007
    ..Understanding these intracellular pathways might lead to new approaches to the treatment of inflammatory disease, including the use of orally bioavailable small molecules that regulate cytokine function and production...
  39. pmc Synoviocyte innate immune responses: I. Differential regulation of interferon responses and the JNK pathway by MAPK kinases
    Toshio Yoshizawa
    Division of Rheumatology, Allergy and Immunology, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA
    J Immunol 181:3252-8. 2008
    ..MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 requires both MKK4 and MKK7, with the former activating c-Jun and the latter activating both c-Jun and IRF3 through JNK-dependent mechanisms...
  40. ncbi request reprint The genetics of the target tissue in rheumatoid arthritis
    Maripat Corr
    Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, School of Medicine, La Jolla, California, USA
    Rheum Dis Clin North Am 28:79-94. 2002
    ..Further studies of large populations are likely to segregate out factors affecting specific ethnic, clinical, and genetic subgroups...
  41. ncbi request reprint Vanadate, an inhibitor of stromelysin and collagenase expression, suppresses collagen induced arthritis
    Stephen J Oliver
    Division of Rheumatology, UCLA School of Medicine, Los Angeles, California, USA
    J Rheumatol 34:1802-9. 2007
    ..We evaluated whether a vanadium AP-1 inhibitor could reduce MMP expression and subsequent joint damage in CIA...
  42. pmc Synoviocyte innate immune responses: II. Pivotal role of IFN regulatory factor 3
    Susan E Sweeney
    Division of Rheumatology, Allergy, and Immunology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
    J Immunol 184:7162-8. 2010
    ..Targeting synoviocyte IRF3 represents a potential approach to suppress diverse mediators while limiting suppression of IRF7-mediated immune responses...
  43. ncbi request reprint PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes
    Hoon Suk Cha
    University of California San Diego, La Jolla, California, USA
    Arthritis Rheum 54:587-92. 2006
    ..To evaluate a method to induce apoptosis, the expression and function of PUMA was investigated in ST and cultured fibroblast-like synoviocytes (FLS)...
  44. ncbi request reprint Inhibiting inflammation in rheumatoid arthritis
    Gary S Firestein
    Division of Rheumatology, Allergy, and Immunology and the University of California at San Diego Clinical Investigation Institute, University of California at San Diego School of Medicine, La Jolla, USA
    N Engl J Med 354:80-2. 2006
  45. ncbi request reprint Spinal adenosine agonist reduces c-fos and astrocyte activation in dorsal horn of rats with adjuvant-induced arthritis
    Linda S Sorkin
    Department of Anesthesiology and Division of Rheumatology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0818, USA
    Neurosci Lett 340:119-22. 2003
    ..Astrocyte activation was only partially attenuated by adenosine A1 receptor agonist treatment...
  46. ncbi request reprint Regulation of peripheral inflammation by spinal adenosine: role of somatic afferent fibers
    Linda S Sorkin
    Department of Anesthesiology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Exp Neurol 184:162-8. 2003
    ..Information on pain and inflammation in the periphery is transmitted to the nervous system, where increased spinal adenosine levels can suppress peripheral inflammation...
  47. pmc Quantitative biomarker analysis of synovial gene expression by real-time PCR
    David L Boyle
    Center for Innovative Therapy, Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, California, USA
    Arthritis Res Ther 5:R352-60. 2003
    ..The technique can potentially be used in serial biopsy studies to provide insights into mechanism of action and therapeutic effect of new anti-inflammatory agents...
  48. ncbi request reprint Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist
    Hal M Hoffman
    Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine, La Jolla, CA 92093 0635, USA
    Lancet 364:1779-85. 2004
    ..The genetic basis of this disease has been elucidated. Cryopyrin, the protein that is altered in FCAS, is one of the adaptor proteins that activate caspase 1, resulting in release of interleukin 1...
  49. ncbi request reprint Rheumatoid arthritis: regulation of synovial inflammation
    Susan E Sweeney
    Division of Rheumatology, Allergy, and Immunology, UCSD School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Int J Biochem Cell Biol 36:372-8. 2004
    ....
  50. ncbi request reprint P53 down-regulates matrix metalloproteinase-1 by targeting the communications between AP-1 and the basal transcription complex
    Yubo Sun
    Department of Medicine, University of Miami School of Medicine, Miami, Florida 33101, USA
    J Cell Biochem 92:258-69. 2004
    ..Finally, by using p53 truncated mutant constructs, we demonstrate that both the N-terminal activation domain and the C-terminal oligomerization domains of p53 were required for the down-regulation of MMP1 transcription...
  51. ncbi request reprint Microsatellite instability and suppressed DNA repair enzyme expression in rheumatoid arthritis
    Sang Heon Lee
    Division of Rheumatology, Allergy, and Immunology, Division of Gastroenterology, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    J Immunol 170:2214-20. 2003
    ..We propose that oxidative stress not only creates DNA adducts that are potentially mutagenic, but also suppresses the mechanisms that limit the DNA damage...
  52. pmc Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis
    Beatrix Bartok
    Division of Rheumatology, Allergy, and Immunology, UCSD School of Medicine, La Jolla, CA 92093, USA
    Immunol Rev 233:233-55. 2010
    ..New agents that target FLS could potentially complement the current therapies without major deleterious effect on adaptive immune responses...
  53. ncbi request reprint Telomerase-transduced osteoarthritic fibroblast-like synoviocyte cell line
    Yubo Sun
    Division of Rheumatology and Immunology, Department of Medicine, University of Miami School of Medicine, Miami, FL 33101, USA
    Biochem Biophys Res Commun 323:1287-92. 2004
    ....
  54. ncbi request reprint HIF-1alpha is essential for myeloid cell-mediated inflammation
    Thorsten Cramer
    Molecular Biology Section, Division of Biological Sciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 112:645-57. 2003
    ..This role for HIF-1alpha demonstrates its direct regulation of survival and function in the inflammatory microenvironment...
  55. pmc Inflammatory mediators promote production of shed LRP1/CD91, which regulates cell signaling and cytokine expression by macrophages
    Matvey Gorovoy
    Department of Pathology, University of California San Diego School of Medicine, La Jolla, CA 92093, USA
    J Leukoc Biol 88:769-78. 2010
    ..7 cells, including TNF-α, MCP-1/CCL2, and IL-10. These results demonstrate that sLRP1 is generated in inflammation and may regulate inflammation by its effects on macrophage physiology...
  56. ncbi request reprint Immunostimulatory DNA sequences influence the course of adjuvant arthritis
    Arash Ronaghy
    Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    J Immunol 168:51-6. 2002
    ..In this model, we postulate that massive and prolonged activation of macrophages, dendritic cells, and osteoclast precursors in the bone marrow may prime the joints for the induction of inflammatory Th1 immune responses to Mtb Ags...
  57. pmc Interactive cytokine regulation of synoviocyte lubricant secretion
    Megan E Blewis
    Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
    Tissue Eng Part A 16:1329-37. 2010
    ....
  58. pmc Role of MAPK kinase 6 in arthritis: distinct mechanism of action in inflammation and cytokine expression
    Toshio Yoshizawa
    Division of Rheumatology, Allergy and Immunology, University of California San Diego, School of Medicine, La Jolla, CA 92093, USA
    J Immunol 183:1360-7. 2009
    ..Although MKK3 and MKK6 activate the p38 pathway, they regulate distinct subsets of proinflammatory cytokines. MKK6 appears mainly to facilitate p38 and MK2 colocalization in the nucleus rather than to phosphorylate p38...
  59. ncbi request reprint Tumor necrosis factor-alpha, an initiator, and etanercept, an inhibitor of cochlear inflammation
    Hitoshi Satoh
    Division of Otolaryngology Head and Neck Surgery, University of California, San Diego, La Jolla 92093 0666, USA
    Laryngoscope 112:1627-34. 2002
    ..Identification of proinflammatory cytokine expression during the initiation of the response should lead to rational therapeutic strategies that block the response, reducing damaging sequelae...
  60. ncbi request reprint TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation
    Ru Liu-Bryan
    Veterans Affairs Medical Center, San Diego, CA 92161, USA
    J Immunol 174:5016-23. 2005
    ..Our results indicate the potential for innate immunity at the level of the articular chondrocyte to directly contribute to inflammatory and degenerative tissue reactions associated with both gout and pseudogout...
  61. pmc Proinflammatory cytokine expression in the endolymphatic sac during inner ear inflammation
    Hitoshi Satoh
    Division of Otolaryngology Head and Neck Surgery, University of California, San Diego, CA 92093, USA
    J Assoc Res Otolaryngol 4:139-47. 2003
    ....
  62. pmc Regional analysis of p53 mutations in rheumatoid arthritis synovium
    Yuji Yamanishi
    Division of Rheumatology, Allergy, and Immunology, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 99:10025-30. 2002
    ..A relatively low percentage of cells containing p53 mutations can potentially affect neighboring cells and enhance inflammation through the elaboration of proinflammatory cytokines...
  63. ncbi request reprint Signal transduction in rheumatoid arthritis
    Susan E Sweeney
    Division of Rheumatology, Allergy, and Immunology, University of California San Diego, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Curr Opin Rheumatol 16:231-7. 2004
    ..Understanding the critical networks in diseases like rheumatoid arthritis can potentially identify novel therapeutic targets...
  64. ncbi request reprint Regulation of arthritis by p53: critical role of adaptive immunity
    Egle Simelyte
    University of California, San Diego, School of Medicine, La Jolla, CA, USA
    Arthritis Rheum 52:1876-84. 2005
    ..To determine if adaptive immune responses or synovial effector functions are responsible for this effect, passive models of arthritis were studied in p53 wild-type and knockout mice...
  65. ncbi request reprint Innate immunity contributes to cochlear adaptive immune responses
    Shigehisa Hashimoto
    Division of Otolaryngology Head and Neck Surgery, University of California, San Diego, 9500 Gilman Dr, CA 92093 0666, USA
    Audiol Neurootol 10:35-43. 2005
    ..If true in humans, this implies that priming may be an important component in the development of immune-mediated hearing loss...
  66. pmc Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement: a randomized, double-blind, placebo-controlled trial
    Dinesh Khanna
    David Geffen School of Medicine, and School of Public Health, University of California, Los Angeles, USA
    Arthritis Rheum 60:1102-11. 2009
    ....
  67. pmc Acoustic trauma augments the cochlear immune response to antigen
    Masumichi Miyao
    Division of Otolaryngology Head and Neck Surgery, University of California, La Jolla, California 92093 0666, USA
    Laryngoscope 118:1801-8. 2008
    ..To test whether noise-exposure, which activates a cochlear immune response with cytokine expression and infiltration of circulating leukocytes could augment the response to antigen (Ag)...
  68. pmc Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis
    Yuji Yamanishi
    University of California at San Diego School of Medicine, La Jolla La Jolla, California 92093, USA
    Am J Pathol 160:123-30. 2002
    ....
  69. ncbi request reprint Synovial tissue analysis in clinical trials
    Barry Bresnihan
    Department of Rheumatology, St Vincent s University Hospital, Dublin, Ireland
    J Rheumatol 32:2481-4. 2005
    ..This special interest group is working on establishing the evidence to have this endpoint meet the OMERACT filter criteria...
  70. ncbi request reprint Amelioration of arthritis by intraarticular dominant negative Ikk beta gene therapy using adeno-associated virus type 5
    Sander W Tas
    Division of Clinical Immunology and Rheumatology, Academic Medical Center University of Amsterdam, 1100 DE Amsterdam, The Netherlands
    Hum Gene Ther 17:821-32. 2006
    ..This translational research represents a crucial next step toward the development of gene therapy for application in humans...
  71. pmc Real-time quantitative PCR to detect changes in synovial gene expression in rheumatoid arthritis after corticosteroid treatment
    Danielle M Gerlag
    Division of Clinical Immunology and Rheumatology, F4 218, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE, Amsterdam, The Netherlands
    Ann Rheum Dis 66:545-7. 2007
    ..These data suggest that Q-PCR can be used to measure synovial mRNA expression of mediators implicated in the pathogenesis of RA in small proof-of-concept trials...
  72. ncbi request reprint Reduction of proinflammatory cytokine expression in the synovium by targeting IKKbeta in vivo in a rat model
    Sander W Tas
    University of Amsterdam, Amsterdam, The Netherlands
    Arthritis Rheum 54:3716-8. 2006
  73. ncbi request reprint Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis show the imprint of synovial tissue heterogeneity: evidence of a link between an increased myofibroblast-like phenotype and high-inflammation synovitis
    Pia V Kasperkovitz
    VU Medical Center, Amsterdam, The Netherlands
    Arthritis Rheum 52:430-41. 2005
    ....
  74. ncbi request reprint Acquisition, culture, and phenotyping of synovial fibroblasts
    Sanna Rosengren
    Methods Mol Med 135:365-75. 2007
    ..Surface markers that can be used to characterize FLS include positive staining for VCAM-1, CD44, CD55, CD90 (Thy-1), and cadherin-11, coupled with the absence of macrophage markers such as CD14 or CD68...
  75. ncbi request reprint NF-kappaB: Holy Grail for rheumatoid arthritis?
    Gary S Firestein
    Arthritis Rheum 50:2381-6. 2004
  76. ncbi request reprint Transforming growth factor beta expression during an inner ear immune response
    Hitoshi Satoh
    Division of Otolaryngology Head and Neck Surgery, University of California San Diego, USA
    Ann Otol Rhinol Laryngol 115:81-8. 2006
    ..The involvement of transforming growth factor beta (TGF-beta), a strong mediator of fibrogenesis, during cochlear immune responses was investigated...
  77. ncbi request reprint A biomarker by any other name
    Gary S Firestein
    Nat Clin Pract Rheumatol 2:635. 2006
  78. ncbi request reprint Regulation of apoptosis in fibroblast-like synoviocytes by the hypoxia-induced Bcl-2 family member Bcl-2/adenovirus E1B 19-kd protein-interacting protein 3
    Wafa Kammouni
    University of Manitoba, Winnipeg, Manitoba, Canada
    Arthritis Rheum 56:2854-63. 2007
    ..Since hypoxia is a regulator of apoptosis, and since RA synovium is hypoxic, we conducted this study to examine the effects of hypoxia on the Bcl-2 pathway and the role this may play in regulating apoptosis in FLS...

Research Grants35

  1. 'c-Jun N-terminal kinase and joint destruction in RA'
    Gary Firestein; Fiscal Year: 2006
    ..Finally, we will determine the role of JNK in animal models of arthritis. These data will support our hypothesis that JNK plays a pivotal role in the FLS biology and is a potential target for chondroprotective therapy. ..
  2. Regulation of p38 and inflammation by MAPK kinases
    Gary Firestein; Fiscal Year: 2007
    ..These studies will provide detailed information on the mechanism of p38 activation in inflammatory arthritis and test the hypothesis that selective targeting of MKKs like MKKS will be beneficial in RA. ..
  3. Training grant in Rheumatic Diseases
    Gary Firestein; Fiscal Year: 2007
    ..The first two hospitals have, in addition, a Clinical Research Center for hospitalization of patients participating in investigational programs. ..
  4. Innate immunity and the IKKi complex in Rheumatoid Arthritis (RA) synovium
    Gary Firestein; Fiscal Year: 2007
    ..These experiments will provide insight into IKK-related kinases and pathogenic mechanisms that contribute to synovitis and joint destruction. ..
  5. Innate immunity and the IKKi complex in Rheumatoid Arthritis (RA) synovium
    Gary Firestein; Fiscal Year: 2009
    ..These experiments will provide insight into IKK-related kinases and pathogenic mechanisms that contribute to synovitis and joint destruction. ..
  6. Regulation of p38 and inflammation by MAPK kinases
    Gary Firestein; Fiscal Year: 2009
    ..These studies will provide detailed information on the mechanism of p38 activation in inflammatory arthritis and test the hypothesis that selective targeting of MKKs like MKKS will be beneficial in RA. ..
  7. Innate immunity and the IKKi complex in Rheumatoid Arthritis (RA) synovium
    GARY STEVEN FIRESTEIN; Fiscal Year: 2010
    ..These experiments will provide insight into IKK-related kinases and pathogenic mechanisms that contribute to synovitis and joint destruction. ..
  8. Regulation of p38 and inflammation by MAPK kinases
    GARY STEVEN FIRESTEIN; Fiscal Year: 2010
    ..These studies will provide detailed information on the mechanism of p38 activation in inflammatory arthritis and test the hypothesis that selective targeting of MKKs like MKKS will be beneficial in RA. ..
  9. c-Jun N-terminal kinase and joint destruction in RA
    GARY STEVEN FIRESTEIN; Fiscal Year: 2010
    ..This project will explore how JNK in RA is regulated by upstream kinases and determine the potential for inhibiting one of these signaling molecules as a therapeutic target. ..
  10. SYNOVIAL DYSFUNCTION DUE TO P53 ABNORMALITIES IN RA
    Gary Firestein; Fiscal Year: 2006
    ..abstract_text> ..
  11. REGULATION OF PERIPHERAL INFLAMMATION BY THE CNS
    Gary Firestein; Fiscal Year: 2002
    ..These studies will provide a basis for understanding the central nervous system-immune system connection as well as explore novel therapeutic targets. ..
  12. SYNOVIAL DYSFUNCTION DUE TO P53 ABNORMALITIES IN RA
    Gary Firestein; Fiscal Year: 2001
    ..A p53-targeted therapeutic approach using a defective adenoviral vector lacking the E1B 55 kD protein will be tested in vivo and in vitro. ..
  13. IKKi expression and regulation in rheumatoid arthritis
    Gary Firestein; Fiscal Year: 2005
    ..We propose to test the hypothesis that IKKi is an important signal transduction pathway that regulates inflammation in chronic arthritis and is a novel target for development of anti-rheumatic agents. ..
  14. Regulation of p38 and inflammation by MAPK kinases
    GARY STEVEN FIRESTEIN; Fiscal Year: 2010
    ..These studies will provide detailed information on the mechanism of p38 activation in inflammatory arthritis and test the hypothesis that selective targeting of MKKs like MKKS will be beneficial in RA. ..