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Genomes and Genes | Fionula BrennanSummaryAffiliation: Imperial College Country: UK Publications
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Publications
The prevention and treatment of murine colitis using gene therapy with adenoviral vectors encoding IL-10J O Lindsay
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, United Kingdom
J Immunol 166:7625-33. 2001..Antiinflammatory cytokine expression protects against immune responses directed at gene vectors...- Evidence that rheumatoid arthritis synovial T cells are similar to cytokine-activated T cells: involvement of phosphatidylinositol 3-kinase and nuclear factor kappaB pathways in tumor necrosis factor alpha production in rheumatoid arthritisFionula M Brennan
Chester Beatty Laboratories, Institute of Cancer Research, London, UK
Arthritis Rheum 46:31-41. 2002..To investigate the mechanism that leads to the spontaneous production of tumor necrosis factor alpha (TNFalpha) in rheumatoid arthritis (RA) synovial tissue... 
Is NF-kappaB a useful therapeutic target in rheumatoid arthritis?M Feldmann
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Charing Cross Hospital Campus, Arthritis Research Campaign Building, 1 Aspenlea Road, London W6 8LH, UK
Ann Rheum Dis 61:ii13-8. 2002..In this brief review we discuss the effects of NF-kappaB blockade in rheumatoid arthritis, inflammation and immunity, and consider possible therapeutic targets within the NF-kappaB family...- Anti-TNFalpha therapy of rheumatoid arthritis: what can we learn about chronic disease?Marc Feldmann
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, London W6 8LH, UK
Novartis Found Symp 256:53-69; discussion 69-73, 106-11, 266-9. 2004..The era of anti-cytokine therapeutics is just dawning... - Targeting rheumatoid tenosynovial angiogenesis with cytokine inhibitorsAbhilash Jain
Department of Musculoskeletal Surgery, Imperial College London, The Charing Cross Hospital Campus, London, UK
Clin Orthop Relat Res 446:268-77. 2006..Level of Evidence: Therapeutic study. Level II (Prospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence... - T-cell contact-dependent regulation of CC and CXC chemokine production in monocytes through differential involvement of NFkappaB: implications for rheumatoid arthritisJonathan T Beech
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
Arthritis Res Ther 8:R168. 2006..Moreover, this study provides further evidence that cytokine-activated T cells share aspects of their effector function with RA synovial T cells and that their targeting in the clinic has therapeutic potential... - Recent developments in the immunobiology of rheumatoid arthritisAnna K Andersson
Kennedy Institute of Rheumatology, Imperial College Faculty of Medicine, 1 Aspenlea Road, London W6 8LH, UK
Arthritis Res Ther 10:204. 2008.... - Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritisFiona E McCann
The Kennedy Institute of Rheumatology, Imperial College London, 65 Aspenlea Road, London, W6 8LH, UK
Arthritis Res Ther 12:R107. 2010..We assessed the anti-inflammatory effects of a novel PDE4 inhibitor, apremilast, in human synovial cells from rheumatoid arthritis (RA) patients, as well as two murine models of arthritis... - Resting CD4+ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell functionFionula M Brennan
Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, Aspenlea Road, London, W6 8LH, UK
Arthritis Res Ther 10:R36. 2008.... - Evidence that cytokines play a role in rheumatoid arthritisFionula M Brennan
Kennedy Institute of Rheumatology, Imperial College London, London, UK
J Clin Invest 118:3537-45. 2008..In this Review, we discuss the biologic contribution and therapeutic potential of the major cytokine families to RA pathology, focusing on molecules contained within the TNF-alpha, IL-1, IL-6, IL-23, and IL-2 families... 
Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanismFionula M Brennan
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK
Eur J Immunol 38:1106-17. 2008..These observations add to our understanding of inflammation and the importance of homeostatic regulators of these events...- Update on cytokines in rheumatoid arthritisFionula Brennan
Kennedy Institute of Rheumatology Division, Imperial College London, London, UK
Curr Opin Rheumatol 19:296-301. 2007..There have recently been fewer publications describing novel cytokines in rheumatoid arthritis. In the present review we focus on cytokines not previously implicated in contributing to the pathogenesis of rheumatoid arthritis... - The importance of T cell interactions with macrophages in rheumatoid cytokine productionF M Brennan
Imperial College of Science, Technology and Medicine, Kennedy Institute of Rheumatology Division, Faculty of Medicine, London, UK
Curr Top Microbiol Immunol 305:177-94. 2006.... - Invasive potential of human rheumatoid tenosynovial cells is in part MT1-MMP dependentAbhilash Jain
Kennedy Institute of Rheumatology Division, Imperial College London, London, UK
J Hand Surg Am 34:1282-90. 2009..The role of MT1-MMP in tendon disease is unknown. In this report, we investigate the potential role of MT1-MMP in invasion of tenosynovium into tendon... - The Toll-like receptor adaptor proteins MyD88 and Mal/TIRAP contribute to the inflammatory and destructive processes in a human model of rheumatoid arthritisSandra M Sacre
Kennedy Institute of Rheumatology, Imperial College London, and the Department of Orthopedics, Royal United Hospital, Bath, UK
Am J Pathol 170:518-25. 2007..Thus, TLRs not only protect against infection but may also promote the inflammatory and destructive process in RA... - SIGIRR/TIR-8 is an inhibitor of Toll-like receptor signaling in primary human cells and regulates inflammation in models of rheumatoid arthritisStefan K Drexler
Imperial College London, London, UK
Arthritis Rheum 62:2249-61. 2010..Therefore, the purpose of this study was to investigate the involvement of SIGIRR in regulating inflammation in disease-relevant models... - Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptorsSandra Sacre
Kennedy Institute of Rheumatology, Imperial College of Science, Technology, and Medicine, London, UK
Arthritis Rheum 62:683-93. 2010..The aim of this study was to assess the antiarthritic potential of 2 SSRIs, fluoxetine and citalopram, in murine collagen-induced arthritis (CIA) and in a human ex vivo disease model of rheumatoid arthritis (RA)... - Cytokine regulation in RA synovial tissue: role of T cell/macrophage contact-dependent interactionsFionula Brennan
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK
Arthritis Res 4:S177-82. 2002..In this chapter, we review recent advances in this area and also highlight areas where new therapeutic intervention opportunities arise... - Cytokine-stimulated T cells induce macrophage IL-10 production dependent on phosphatidylinositol 3-kinase and p70S6K: implications for rheumatoid arthritisAndrew Foey
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, Hammersmith, London, W6 8LH, UK
Arthritis Res 4:64-70. 2002..IL-10 production in RA-SMCs and M-CSF-primed macrophages, activated by interaction with Tck, is PI3K- and p70S6K-dependent... - Rac mediates TNF-induced cytokine production via modulation of NF-kappaBLynn M Williams
Kennedy Institute of Rheumatology Division, Imperial College London, Hammersmith, London W6 8LH, United Kingdom
Mol Immunol 45:2446-54. 2008..This would suggest that TNF-induced activation of Rac, lies upstream of NF-kappaB activation, and that the inhibition of this pathway results in inhibition of cytokine production... - Expression of constitutively active STAT3 can replicate the cytokine-suppressive activity of interleukin-10 in human primary macrophagesLynn M Williams
Kennedy Institute of Rheumatology Division, Imperial College London, ARC Building, 1 Aspenlea Road, London W6 8LH, United Kingdom
J Biol Chem 282:6965-75. 2007..However, in synovial fibroblasts, STAT3 did not suppress IL-6 production, suggesting that the cellular environment plays an important role in dictating whether STAT3 drives a pro- or anti-inflammatory response... - The role of matrix metalloproteinases in rheumatoid tendon diseaseAbhilash Jain
Department of Musculoskeletal Surgery and the Kennedy Institute of Rheumatology, Imperial College School of Medicine, The Charing Cross Hospital Campus, London, UK
J Hand Surg [Am] 27:1059-64. 2002..These results show that invasive tenosynovium is more destructive than encapsulating tenosynovium at a molecular level, providing an explanation for the increased tendon rupture associated with invasive tenosynovitis in RA... - NF-kappaB-inducing kinase is dispensable for activation of NF-kappaB in inflammatory settings but essential for lymphotoxin beta receptor activation of NF-kappaB in primary human fibroblastsC Smith
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, Hammersmith, London, United Kingdom
J Immunol 167:5895-903. 2001..These data also highlight the potential problems in extrapolating the function of signaling pathways between primary and transfected cell lines... - Suppression of tumour necrosis factor production from mononuclear cells by a novel synthetic compound, CLX-090717P F Sumariwalla
Kennedy Institute of Rheumatology, Imperial College London, London, UK
Rheumatology (Oxford) 48:32-8. 2009..To evaluate the clinical efficacy of a novel synthetic peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, CLX-090717, in several in vitro cell culture systems and murine CIA, an experimental model of RA... - Route of monocyte differentiation determines their cytokine production profile: CD40 ligation induces interleukin 10 expressionA D Foey
Kennedy Institute of Rheumatology, 1 Aspenlea Road, Hammersmith, London, W6 8LH, UK
Cytokine 12:1496-505. 2000..These data indicate that CD40 ligation regulates cell contact mediated macrophage IL-10 and that the route of differentiation determines the cytokine profile... - Cytokine blockade in rheumatoid arthritisM Feldmann
Kennedy Institute of Rheumatology, Hammersmith, London, UK
Adv Exp Med Biol 490:119-27. 2001..New approaches to studying TNF regulation in RA and of elucidating the controversial role of T cells in this complex disease will be described... - Neutralizing IL-21 and IL-15 inhibits pro-inflammatory cytokine production in rheumatoid arthritisA K Andersson
Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, London, UK
Scand J Immunol 68:103-11. 2008..The data confirm that IL-15 plays a role in RA and suggests that IL-21 is also involved in driving the pro-inflammatory cytokine response in RA... - High efficiency gene transfer is an efficient way of defining therapeutic targets: a functional genomics approachB M Foxwell
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, UK
Ann Rheum Dis 60:iii13-7. 2001..Studying the intracellular signalling mechanism used by dendritic cells would provide an insight into the functioning of these cells and give clues to strategies for immunomodulation... - Treatment of rheumatoid tenosynovitis with cytokine inhibitorsAbhilash Jain
Department of Musculoskeletal Surgery, Imperial College School of Medicine, Charing Cross Hospital Campus, Arthritis Research Campaign Building, London, UK
Lancet 360:1565-6. 2002..Our data show that cytokine blockade can reduce collagenase concentrations in tenosynovial tissue, suggesting cytokine inhibitors could be effective in reduction of tendon damage... - Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint diseaseKim Midwood
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK
Nat Med 15:774-80. 2009..Thus, we have identified tenascin-C as a novel endogenous activator of TLR4-mediated immunity that mediates persistent synovial inflammation and tissue destruction in arthritic joint disease... - Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitisJ O Lindsay
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 1 Aspenlea Road, London W6 8LH, UK
Gut 52:981-7. 2003.... - Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitisJ O Lindsay
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, UK
Gut 52:363-9. 2003.... - Antigen-specific T-cell downregulation by human dendritic cells following blockade of NF-kappaBV L Calder
Institute of Ophthalmology, UCL, London, UK
Scand J Immunol 57:261-70. 2003..The effective downregulation of antigen-specific T-cell responses following blockade of NF-kappaB in DCs could be a useful approach for immunomodulating inflammatory T-cell responses... - CD40 ligation induces macrophage IL-10 and TNF-alpha production: differential use of the PI3K and p42/44 MAPK-pathwaysA D Foey
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, UK
Cytokine 16:131-42. 2001..These observations suggest that CD40 ligation induces macrophage IL-10 and TNF-alpha production, the mechanism of which is p70S6K-dependent yet bifurcates at the level of PI3K and p42/44 MAPK... - A follow-up to "Anti-cytokine therapy in chronic destructive arthritis" by Wim B van den BergF M Brennan
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, Hammersmith, London, UK
Arthritis Res 3:211-3; discussion 214-5. 2001..More broadly, it discusses the biology of TNF-alpha and IL-1 and suggests explanations of why TNF-alpha is a pivotal cytokine in this disease... - Role of NFkappaB in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with the proteasome inhibitor PSIS Yoshimura
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, GB
Eur J Immunol 31:1883-93. 2001.... - Effective antigen presentation by dendritic cells is NF-kappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokinesS Yoshimura
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
Int Immunol 13:675-83. 2001.... - Antigen presentation by murine dendritic cells is nuclear factor-kappa B dependent both in vitro and in vivoS Yoshimura
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
Scand J Immunol 58:165-72. 2003..This finding has potential implications for the development of therapeutic agents for use in various pathological conditions of the immune system, including allergy and autoimmunity, and also in transplantation... - Cytokines in autoimmunityF M Brennan
Kennedy Institute of Rheumatology, Hammersmith, London, UK
Curr Opin Immunol 8:872-7. 1996..Recent contributions to this field, derived from in vivo studies in animal models of autoimmunity, and increasingly from clinical trials, have greatly enhanced our understanding of this field... - Ikappa B kinase 2 but not NF-kappa B-inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reactionEvangelos Andreakos
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom
Blood 101:983-91. 2003..In addition, our results support IKK2 as a potential therapeutic target for the down-regulation of unwanted immune responses that may occur during transplantation or autoimmunity... - Cytokines and anti-cytokine biologicals in autoimmunity: present and futureEvangelos T Andreakos
Faculty of Medicine, Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
Cytokine Growth Factor Rev 13:299-313. 2002..The future developments of anti-TNFalpha and anti-cytokine therapy in general will be interesting... - Conventional protein kinase C and atypical protein kinase Czeta differentially regulate macrophage production of tumour necrosis factor-alpha and interleukin-10Andrew D Foey
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, UK
Immunology 112:44-53. 2004.... - High-efficiency gene transfer into nontransformed cells: utility for studying gene regulation and analysis of potential therapeutic targetsNicole J Horwood
Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, London, UK
Arthritis Res 4:S215-25. 2002..While the NF-kappaB pathway has proven to be a major mediator of tumour necrosis factor alpha production, it is not exclusive and work evaluating the involvement of other pathways is ongoing... - Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alphaMichael J Elliot
Clinical Immunology Division, Kennedy Institute of Rheumatology, London W6 7DW, United Kingdom
Arthritis Rheum 58:S92-S101. 2008..To evaluate the safety and efficacy of a chimeric monoclonal antibody to tumor necrosis factor alpha (TNF alpha) in the treatment of patients with rheumatoid arthritis (RA)... - Preparation of mononuclear cells from synovial tissueJonathan T Beech
Methods Mol Med 135:105-19. 2007.... - A novel mechanism for TNF-alpha regulation by p38 MAPK: involvement of NF-kappa B with implications for therapy in rheumatoid arthritisJamie Campbell
Kennedy Institute of Rheumatology Division, Imperial College School of Medicine Hammersmith, London, United Kingdom
J Immunol 173:6928-37. 2004..These results indicate despite disappointing results with p38 MAPK inhibitors in the clinic, this kinase is a valid target in rheumatoid disease... - Lung-marginated monocytes modulate pulmonary microvascular injury during early endotoxemiaArnold J Young
Department of Anaesthetics and Intensive Care, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK
Am J Respir Crit Care Med 172:1119-27. 2005.... - Anti-TNF therapy: where have we got to in 2005?Marc Feldmann
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, 1 Aspenlea Road, London W6 8LH, UK
J Autoimmun 25:26-8. 2005..There are still many limitations, but the prospects for the future are intriguing... - Impact of VIP and cAMP on the regulation of TNF-alpha and IL-10 production: implications for rheumatoid arthritisAndrew D Foey
Kennedy Institute of Rheumatology Division, Charing Cross Hospital Campus, Imperial College School of Medicine, London, UK
Arthritis Res Ther 5:R317-28. 2003..In conclusion, VIP may represent an efficaceous anti-arthritic treatment modulating macrophage and T-cell cytokine profiles when used alongside a phosphodiesterase inhibitor... - The transfer of a laboratory based hypothesis to a clinically useful therapy: the development of anti-TNF therapy of rheumatoid arthritisMarc Feldmann
Kennedy Institute of Rheumatology Division, Imperial College, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
Best Pract Res Clin Rheumatol 18:59-80. 2004..The development of anti-TNF therapy is a key step forward in rheumatology as it is the first new therapy for based on investigating the molecular mechanisms of this disease. This chapter reviews how this discovery was made... - Heterogeneous requirement of IkappaB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: implications for therapyEvangelos Andreakos
Kennedy Institute of Rheumatology, Imperial College of Science, Technology and Medicine, London, UK
Arthritis Rheum 48:1901-12. 2003.... - TCRzetadim lymphocytes define populations of circulating effector cells that migrate to inflamed tissuesZhuoli Zhang
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, Hammersmith, London, United Kingdom
Blood 109:4328-35. 2007..Taken together, the functional properties of TCRzeta(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease... - Could toll-like receptors provide a missing link in chronic inflammation in rheumatoid arthritis? Lessons from a study on human rheumatoid tissueSandra M Sacre
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
Ann Rheum Dis 66:iii81-6. 2007.... - Bruton's tyrosine kinase is required for TLR2 and TLR4-induced TNF, but not IL-6, productionNicole J Horwood
Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Charing Cross Campus, 1 Aspenlea Road, London W6 8LH, United Kingdom
J Immunol 176:3635-41. 2006.... - Bruton's tyrosine kinase is required for lipopolysaccharide-induced tumor necrosis factor alpha productionNicole J Horwood
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London W6 8LH, United Kingdom
J Exp Med 197:1603-11. 2003.... - Molecular profile of peripheral blood mononuclear cells from patients with rheumatoid arthritisChristopher J Edwards
The Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, UK
Mol Med 13:40-58. 2007..3. These results suggest that analysis of RA PBMCs at the molecular level may provide a set of candidate genes that could yield an easily accessible gene signature to aid in early diagnosis and treatment...