ArticleThe Journal of biological chemistry2015
Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Acute Strenuous Exercise Induces an Imbalance on Histone H4 Acetylation/Histone Deacetylase 2 and Increases the Proinflammatory Profile of PBMC of Obese Individuals.Oxidative medicine and cellular longevity · 2017Trial
- The epigenetic landscape of rheumatoid arthritis: Pathogenesis and drug therapeutic potentials.Acta pharmaceutica Sinica. B · 2025Review
- Substrate-Guided Development of HDAC11-Selective Inhibitors Featuring α‑Amino Amide Zinc-Binding Groups.ACS omega · 2025Article
- Hitting Two Birds With One Stone: Dual Modulation of Brain Carbonic Anhydrases and Histone Deacetylases Boosts Memory Consolidation.Archiv der Pharmazie · 2025Article
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeted intervention of tumor microenvironment with HDAC inhibitors and their combination therapy strategies.European journal of medical research · 2025Review
- UPLC-MS/MS Method for Givinostat in Rat Plasma: Development, Validation, in vivo Pharmacokinetics Study and in vitro Metabolic Stability Research.Drug design, development and therapy · 2025Article
- Micro- and nano-plastics induce inflammation and cell death in human cells.Frontiers in immunology · 2025Article
- Inhibitor Development for α-Synuclein Fibril's Disordered Region to Alleviate Parkinson's Disease Pathology.Journal of the American Chemical Society · 2024Article
- The Role of Histone Deacetylases in NLRP3 Inflammasomesmediated Epilepsy.Current molecular medicine · 2024Review
- Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Histone deacetylase-2 controls IL-1β production through the regulation of NLRP3 expression and activation in tuberculosis infection.iScience · 2022Article
- Analysis of Givinostat/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage.International journal of molecular sciences · 2022Article
- Review
- Role of Histone Deacetylases in Monocyte Function in Health and Chronic Inflammatory Diseases.Reviews of physiology, biochemistry and pharmacology · 2021Review
- MiR-451a ameliorates alcoholic hepatitis via repressing HDAC8-mediated proinflammatory response.The Kaohsiung journal of medical sciences · 2020Article
- Givinostat: an emerging treatment for polycythemia vera.Expert opinion on investigational drugs · 2020Review
- HDAC3 Mediates the Inflammatory Response and LPS Tolerance in Human Monocytes and Macrophages.Frontiers in immunology · 2020Article
- The role of cigarette smoke-induced epigenetic alterations in inflammation.Epigenetics & chromatin · 2019Review
- Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue.ChemMedChem · 2019Article
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Authors and funding
11 authors.
Funding
Abstract
ITF2357 (generic givinostat) is an orally active, hydroxamic-containing histone deacetylase (HDAC) inhibitor with broad anti-inflammatory properties, which has been used to treat children with systemic juvenile idiopathic arthritis. ITF2357 inhibits both Class I and II HDACs and reduces caspase-1 activity in human peripheral blood mononuclear cells and the secretion of IL-1β and other cytokines at 25-100 nm; at concentrations >200 nm, ITF2357 is toxic in vitro. ITF3056, an analog of ITF2357, inhibits only HDAC8 (IC50 of 285 nm). Here we compared the production of IL-1β, IL-1α, TNFα, and IL-6 by ITF2357 with that of ITF3056 in peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS), heat-killed Candida albicans, or anti-CD3/anti-CD28 antibodies. ITF3056 reduced LPS-induced cytokines from 100 to 1000 nm; at 1000 nm, the secretion of IL-1β was reduced by 76%, secretion of TNFα was reduced by 88%, and secretion of IL-6 was reduced by 61%. The intracellular levels of IL-1α were 30% lower. There was no evidence of cell toxicity at ITF3056 concentrations of 100-1000 nm. Gene expression of TNFα was markedly reduced (80%), whereas IL-6 gene expression was 40% lower. Although anti-CD3/28 and Candida stimulation of IL-1β and TNFα was modestly reduced, IFNγ production was 75% lower. Mechanistically, ITF3056 reduced the secretion of processed IL-1β independent of inhibition of caspase-1 activity; however, synthesis of the IL-1β precursor was reduced by 40% without significant decrease in IL-1β mRNA levels. In mice, ITF3056 reduced LPS-induced serum TNFα by 85% and reduced IL-1β by 88%. These data suggest that specific inhibition of HDAC8 results in reduced inflammation without cell toxicity.
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