ArticleToxicology and applied pharmacology2013
Largazole, a class I histone deacetylase inhibitor, enhances TNF-α-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts.
Article in Toxicology and applied pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 40 citations in OpenAlex.
- Antioxidant, Anti-Inflammatory and Anticancer Peptides from Extreme Marine Environments.Antioxidants (Basel, Switzerland) · 2026Review
- Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions.Military Medical Research · 2026Review
- Immune regulation of Chidamide-induced Linc01010 accumulation in breast cancer cell death.World journal of clinical oncology · 2025Article
- 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
- Epi-revolution in rheumatology: the potential of histone deacetylase inhibitors for targeted rheumatoid arthritis intervention.Inflammopharmacology · 2024Review
- Unveiling Novel Drug Targets and Emerging Therapies for Rheumatoid Arthritis: A Comprehensive Review.ACS pharmacology & translational science · 2024Review
- Signaling pathways in rheumatoid arthritis: implications for targeted therapy.Signal transduction and targeted therapy · 2023Review
- M-134, a novel HDAC6-selective inhibitor, markedly improved arthritic severity in a rodent model of rheumatoid arthritis when combined with tofacitinib.Pharmacological reports : PR · 2021Article
- Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Epigenetic Regulations of AhR in the Aspect of Immunomodulation.International journal of molecular sciences · 2020Review
- Marine Cyanobacteria: A Source of Lead Compounds and their Clinically-Relevant Molecular Targets.Molecules (Basel, Switzerland) · 2020Review
- Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fibroblasts and Endothelial Cells.Frontiers in immunology · 2020Article
- Inhibition of HDAC6 alleviating lipopolysaccharide-induced p38MAPK phosphorylation and neuroinflammation in mice.Pharmaceutical biology · 2019Article
- The emerging role of epigenetics in human autoimmune disorders.Clinical epigenetics · 2019Review
- Review
- Hydroxysafflor yellow A attenuates the expression of inflammatory cytokines in acute soft tissue injury.Scientific reports · 2017Article
- Largazole Analogues Embodying Radical Changes in the Depsipeptide Ring: Development of a More Selective and Highly Potent Analogue.Journal of medicinal chemistry · 2016Article
- Molecular mechanisms of suberoylanilide hydroxamic acid in the inhibition of TGF-β1-mediated canine corneal fibrosis.Veterinary ophthalmology · 2016Article
- Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis: results from the COMBINE study.Molecular medicine (Cambridge, Mass.) · 2016Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
In the present study, we evaluated the effect of largazole (LAR), a marine-derived class I HDAC inhibitor, on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) activity. LAR (1-5 μM) had no adverse effect on the viability of RA synovial fibroblasts. Among the different class I HDACs screened, LAR (0.5-5 μM) inhibited the constitutive expression of HDAC1 (0-30%). Surprisingly, LAR increased class II HDAC [HDAC6] by ~220% with a concomitant decrease in HDAC5 [30-58%] expression in RA synovial fibroblasts. SAHA (5 μM), a pan-HDAC inhibitor, also induced HDAC6 expression in RA synovial fibroblasts. Pretreatment of RA synovial fibroblasts with LAR further enhanced TNF-α-induced ICAM-1 and VCAM-1 expression. However, LAR inhibited TNF-α-induced MMP-2 activity in RA synovial fibroblasts by 35% when compared to the TNF-α-treated group. Further, the addition of HDAC6 specific inhibitor Tubastatin A with LAR suppressed TNF-α+LAR-induced ICAM-1 and VCAM-1 expression and completely blocked MMP-2 activity, suggesting a role of HDAC6 in LAR-induced ICAM-1 and VCAM-1 expression. LAR also enhanced TNF-α-induced phospho-p38 and phospho-AKT expression, but inhibited the expression of phospho-JNK and nuclear translocation of NF-κBp65 in RA synovial fibroblasts. These results suggest that LAR activates p38 and Akt pathways and influences class II HDACs, in particular HDAC6, to enhance some of the detrimental effects of TNF-α in RA synovial fibroblasts. Understanding the exact role of different HDAC isoenzymes in RA pathogenesis is extremely important in order to develop highly effective HDAC inhibitors for the treatment of RA.
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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.