ArticleInternational journal of molecular sciences2020
Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Epigenetic programming of macrophages across inflammatory and malignant diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Decoding Epigenetic Switches: How Histone Acetylation/Deacetylation Regulates Mononuclear/Macrophage Fate in Bone Disorders.International journal of biological sciences · 2026Review
- Rewiring immunity in rheumatoid arthritis: metabolic and epigenetic therapeutic strategies.Frontiers in pharmacology · 2026Review
- Overcoming immunotherapy barriers in pediatric brain tumors: epigenetic strategies.Frontiers in oncology · 2026Review
- Dose-dependent dual effects of HDAC inhibitors on glial inflammatory response.Scientific reports · 2025Article
- Review
- The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods.Pharmaceuticals (Basel, Switzerland) · 2024Review
- HDAC6-selective inhibitor CAY10603 ameliorates cigarette smoke-induced small airway remodeling by regulating epithelial barrier dysfunction and reversing.Respiratory research · 2024Article
- The Antioxidant Effect of Dietary Bioactives Arises from the Interplay between the Physiology of the Host and the Gut Microbiota: Involvement of Short-Chain Fatty Acids.Antioxidants (Basel, Switzerland) · 2023Review
- Involvement of epigenetics in affecting host immunity during SARS-CoV-2 infection.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- HDAC-an important target for improving tumor radiotherapy resistance.Frontiers in oncology · 2023Review
- Pan HDACi Valproic Acid and Trichostatin A Show Apparently Contrasting Inflammatory Responses in Cultured J774A.1 Macrophages.Epigenomes · 2022Article
- Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches.Virus research · 2022Review
- Inhibition of Class I Histone Deacetylase Activity Blocks the Induction of TNFAIP3 Both Directly and Indirectly via the Suppression of Endogenous TNF-α.International journal of molecular sciences · 2022Article
- Inflammation in Health and Disease: New Insights and Therapeutic Avenues.International journal of molecular sciences · 2022Article
- Harnessing anti-tumor and tumor-tropism functions of macrophages via nanotechnology for tumor immunotherapy.Exploration (Beijing, China) · 2022Review
- Preclinical Efficacy and Toxicity Analysis of the Pan-Histone Deacetylase Inhibitor Gossypol for the Therapy of Colorectal Cancer or Hepatocellular Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Review
- Histone deacetylase inhibition reduces deleterious cytokine release induced by ingenol stimulation.Biochemical pharmacology · 2022Article
- Histone Modification in NSCLC: Molecular Mechanisms and Therapeutic Targets.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on IκB kinase epsilon (IKKε) which has not been investigated in this context before. Therefore, we applied the pan-HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) as well as HDAC-specific siRNA. Administration of HDACi reduced HDAC activity and decreased expression of IKKε although its acetylation was increased. Other pro-inflammatory genes (IL-1β, iNOS, TNFα) also decreased while COX-2 expression increased. HDAC 2, 3 and 4, respectively, might be involved in IKKε and iNOS downregulation with potential participation of NF-κB transcription factor inhibition. Suppression of HDAC 1-3, activation of NF-κB and RNA stabilization mechanisms might contribute to increased COX-2 expression. In conclusion, our results indicate that TSA and SAHA exert a number of histone- and HDAC-independent functions. Furthermore, the data show that different HDAC enzymes fulfill different functions in macrophages and might lead to both pro- and anti-inflammatory effects which have to be considered in therapeutic approaches.
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