ArticleThe Journal of biological chemistry2016
Inhibition of Interleukin 1β (IL-1β) Expression by Anthrax Lethal Toxin (LeTx) Is Reversed by Histone Deacetylase 8 (HDAC8) Inhibition in Murine Macrophages.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Differential effects of HDAC8 targeting on Foxp3+ Tregs and effector T cells promote antitumor immunity.JCI insight · 2026Article
- Future applications of host direct therapies for infectious disease treatment.Frontiers in immunology · 2024Review
- Pulmonary Pathogen-Induced Epigenetic Modifications.Epigenomes · 2023Review
- Pathological Role of HDAC8: Cancer and Beyond.Cells · 2022Review
- HDAC8 suppresses the epithelial phenotype and promotes EMT in chemotherapy-treated basal-like breast cancer.Clinical epigenetics · 2022Article
- Lysine Deacetylase Substrate Selectivity: A Dynamic Ionic Interaction Specific to KDAC8.Biochemistry · 2021Article
- Role of Epigenetics in the Regulation of Immune Functions of the Skin.The Journal of investigative dermatology · 2021Review
- HDAC8 Inhibition Reduces Lesional Iba-1+ Cell Infiltration after Spinal Cord Injury without Effects on Functional Recovery.International journal of molecular sciences · 2020Article
- Histone hyperacetylation mediates enhanced IL-1β production in LPS/IFN-γ-stimulated macrophages.Immunology · 2020Article
- Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition.Beilstein journal of organic chemistry · 2020Article
- HDAC3 Regulates Gingival Fibroblast Inflammatory Responses in Periodontitis.Journal of dental research · 2020Article
- The transcription factor PU.1 mediates enhancer-promoter looping that is required for IL-1β eRNA and mRNA transcription in mouse melanoma and macrophage cell lines.The Journal of biological chemistry · 2019Article
- Epigenetic regulation in bacterial infections: targeting histone deacetylases.Critical reviews in microbiology · 2018Review
- The Novel HDAC8 Inhibitor WK2-16 Attenuates Lipopolysaccharide-Activated Matrix Metalloproteinase-9 Expression in Human Monocytic Cells and Improves Hypercytokinemia In Vivo.International journal of molecular sciences · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many pathogenic microbes often release toxins that subvert the host's immune responses to render the environment suitable for their survival and proliferation. LeTx is one of the toxins causing immune paralysis by cleaving and inactivating the mitogen-activated protein kinase (MAPK) kinases (MEKs). Here, we show that inhibition of the histone deacetylase 8 (HDAC8) by either the HDAC8-specific inhibitor PCI-34051 or small interference (si)RNAs rendered LeTx-exposed murine macrophages responsive to LPS in pro-IL-1β production. HDAC8 selectively targeted acetylated histone H3 lysine 27 (H3K27Ac), which is known to associate with active enhancers. LeTx induced HDAC8 expression, in part through inhibiting p38 MAPK, which resulted in a decrease of H3K27Ac levels. Inhibition of HDAC8 increased H3K27Ac levels and enhanced NF-κB-mediated pro-IL-1β enhancer and messenger RNA production in LeTx-exposed macrophages. Collectively, this study demonstrates a novel role of HDAC8 in LeTx immunotoxicity and regulation of pro-IL-1β production likely through eRNAs. Targeting HDAC8 could be a strategy for enhancing immune responses in macrophages exposed to LeTx or other toxins that inhibit MAPKs.
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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.