ArticleArthritis and rheumatism2012
Histone deacetylases are dysregulated in rheumatoid arthritis and a novel histone deacetylase 3-selective inhibitor reduces interleukin-6 production by peripheral blood mononuclear cells from rheumatoid arthritis patients.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 146 citations in OpenAlex.
- The epigenetic landscape of rheumatoid arthritis: Pathogenesis and drug therapeutic potentials.Acta pharmaceutica Sinica. B · 2025Review
- Histone Deacetylases (HDACs) Roles in Inflammation-mediated Diseases; Current Knowledge.Cell biochemistry and biophysics · 2025Review
- Targeting BRD4 to attenuate RANKL-induced osteoclast activation and bone erosion in rheumatoid arthritis.Molecular and cellular biochemistry · 2025Article
- Epi-revolution in rheumatology: the potential of histone deacetylase inhibitors for targeted rheumatoid arthritis intervention.Inflammopharmacology · 2024Review
- A TLR4/TRAF6-dependent signaling pathway mediates NCoR coactivator complex formation for inflammatory gene activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of HDAC3 in inflammation: mechanisms and therapeutic implications.Frontiers in immunology · 2024Review
- Autoimmune disease: a view of epigenetics and therapeutic targeting.Frontiers in immunology · 2024Review
- The effect of epigenetic reprogramming using MI192 HDAC inhibitor on enhancing the osteogenesis of human adipose-derived stem cells in vitro.Bioscience reports · 2023Article
- Signaling pathways in rheumatoid arthritis: implications for targeted therapy.Signal transduction and targeted therapy · 2023Review
- Pan HDACi Valproic Acid and Trichostatin A Show Apparently Contrasting Inflammatory Responses in Cultured J774A.1 Macrophages.Epigenomes · 2022Article
- HDAC1 regulates inflammation and osteogenic differentiation of ankylosing spondylitis fibroblasts through the Wnt-Smad signaling pathway.Journal of orthopaedic surgery and research · 2022Article
- Abnormal Histones Acetylation in Patients with Primary Sjögren's Syndrome.Clinical rheumatology · 2022Article
- Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis.Frontiers in medicine · 2022Article
- Identification of Tissue-Specific Expressed Hub Genes and Potential Drugs in Rheumatoid Arthritis Using Bioinformatics Analysis.Frontiers in genetics · 2022Article
- Inhibition of histone deacetylase 6 suppresses inflammatory responses and invasiveness of fibroblast-like-synoviocytes in inflammatory arthritis.Arthritis research & therapy · 2021Article
- The Selective Histone Deacetylase Inhibitor MI192 Enhances the Osteogenic Differentiation Efficacy of Human Dental Pulp Stromal Cells.International journal of molecular sciences · 2021Article
- Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives.Journal of personalized medicine · 2021Review
- Etiology and Risk Factors for Rheumatoid Arthritis: A State-of-the-Art Review.Frontiers in medicine · 2021Review
- Epigenetic Regulations of AhR in the Aspect of Immunomodulation.International journal of molecular sciences · 2020Review
- The inflammatory effect of epigenetic factors and modifications in type 2 diabetes.Inflammopharmacology · 2020Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveTo characterize the role of histone deacetylase (HDAC) activity in rheumatoid arthritis (RA) and to evaluate the effects of MI192, a novel HDAC-3-selective inhibitor, compared with the established nonselective HDAC inhibitor trichostatin A (TSA), on proinflammatory cytokine production.
methodsActivity of HDAC and histone acetyltransferase was measured in peripheral blood mononuclear cells (PBMCs) from RA patients by spectrophotometric assay, prior to and after 12 weeks of etanercept therapy. The effects of HDAC inhibitor treatment on cytokine production in both RA and healthy PBMCs were assessed by enzyme-linked immunosorbent assay.
resultsRA PBMCs exhibited significantly increased HDAC activity (P = 0.007) compared to PBMCs from healthy individuals, and the increase was unaltered after 12 weeks of etanercept therapy. TSA was a potent inhibitor of tumor necrosis factor (TNF) and interleukin-6 (IL-6) production in both RA and healthy PBMCs and of interferon-γ (IFNγ) production in healthy PBMCs; IFNγ was not produced by RA PBMCs. MI192 inhibited TNF production at high concentrations and dose-dependently inhibited IL-6 in RA PBMCs but not healthy PBMCs, across a dose range of 10 μM-5 nM.
conclusionHDAC activity is dysregulated in RA PBMCs and is a potential target for therapeutic intervention, as it is not affected by conventional anti-TNF treatment with etanercept. Both the selective and the nonselective HDAC inhibitors (MI192 and TSA, respectively) were found to regulate cytokine production from PBMCs, but their effects were cell type and compound specific. HDAC inhibitors have potential in the treatment of RA, and HDAC-selective inhibition may improve the therapeutic margin of safety; however, further clinical characterization and evaluation for adverse effects is needed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.