tailieunhanh - Báo cáo y học: "Targeting histone deacetylase activity in rheumatoid arthritis and asthma as prototypes of inflammatory disease: should we keep our HATs on"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Targeting histone deacetylase activity in rheumatoid arthritis and asthma as prototypes of inflammatory disease: should we keep our HATs on? | Available online http content 10 5 226 Review Targeting histone deacetylase activity in rheumatoid arthritis and asthma as prototypes of inflammatory disease should we keep our HATs on Aleksander M Grabiec Paul P Tak and Kris A Reedquist Division of Clinical Immunology and Rheumatology Academic Medical Center University of Amsterdam Meibergdreef 9 1105 AZ Amsterdam The Netherlands Corresponding author Kris A Reedquist Published 17 October 2008 This article is online at http content 10 5 226 2008 BioMed Central Ltd Arthritis Research Therapy 2008 10 226 doi ar2489 Abstract Cellular activation proliferation and survival in chronic inflammatory diseases is regulated not only by engagement of signal transduction pathways that modulate transcription factors required for these processes but also by epigenetic regulation of transcription factor access to gene promoter regions. Histone acetyl transferases coordinate the recruitment and activation of transcription factors with conformational changes in histones that allow gene promoter exposure. Histone deacetylases HDACs counteract histone acetyl transferase activity through the targeting of both histones as well as nonhistone signal transduction proteins important in inflammation. Numerous studies have indicated that depressed HDAC activity in patients with inflammatory airway diseases may contribute to local proinflammatory cytokine production and diminish patient responses to corticosteroid treatment. Recent observations that HDAC activity is depressed in rheumatoid arthritis patient synovial tissue have predicted that strategies restoring HDAC function may be therapeutic in this disease as well. Pharmacological inhibitors of HDAC activity however have demonstrated potent therapeutic effects in animal models of arthritis and other chronic inflammatory diseases. In the present review we assess and reconcile these outwardly paradoxical study .

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