ArticleEuropean journal of immunology2015
BET bromodomain inhibition suppresses transcriptional responses to cytokine-Jak-STAT signaling in a gene-specific manner in human monocytes.
Article in European journal of immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 83 citations in OpenAlex.
- A randomized study of the safety and pharmacokinetics of GSK3358699, a mononuclear myeloid-targeted bromodomain and extra-terminal domain inhibitor.British journal of clinical pharmacology · 2022Trial
- Knockdown of SOX4 attenuates sepsis myocardial injury by inhibiting the EZH2/H3K27me3/SOCS3 axis.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- A comprehensive analysis of epigenetic mechanisms regulating inflammation-induced TNF-α gene expression by small-molecule inhibitor screening.Molecular biology reports · 2026Article
- Bromodomain and extra-terminal protein inhibitors modulate natural killer cell function and differentiation.Scientific reports · 2026Article
- In vivo generation of CAR macrophages via the enucleated mesenchymal stem cell delivery system for glioblastoma therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions.Frontiers in oncology · 2025Review
- Acetylation-Mediated Epigenetic Consequences for Biological Control and Cancer.Results and problems in cell differentiation · 2025Review
- Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition.iScience · 2024Article
- The BET degrader ZBC260 suppresses stemness and tumorigenesis and promotes differentiation in triple-negative breast cancer by disrupting inflammatory signaling.Breast cancer research : BCR · 2023Article
- Review
- Modulation of macrophage inflammatory function through selective inhibition of the epigenetic reader protein SP140.BMC biology · 2022Article
- BET protein inhibition promotes non-myeloid cell mediated neuroprotection after rodent spinal cord contusion.Experimental neurology · 2022Article
- Effects of inhibiting astrocytes and BET/BRD4 chromatin reader on spatial memory and synaptic proteins in rats with Alzheimer's disease.Metabolic brain disease · 2022Article
- An in silico analysis identifies drugs potentially modulating the cytokine storm triggered by SARS-CoV-2 infection.Scientific reports · 2022Article
- Bromodomain Inhibitors Modulate FcγR-Mediated Mononuclear Phagocyte Activation and Chemotaxis.Frontiers in immunology · 2022Article
- BAF155 methylation drives metastasis by hijacking super-enhancers and subverting anti-tumor immunity.Nucleic acids research · 2021Article
- Paradigm shift in the pathogenesis and treatment of oral cancer and other cancers focused on the oralome and antimicrobial-based therapeutics.Periodontology 2000 · 2021Review
- Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis.Cells · 2021Review
- Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives.Journal of personalized medicine · 2021Review
- High-Throughput Screening for CEBPD-Modulating Compounds in THP-1-Derived Reporter Macrophages Identifies Anti-Inflammatory HDAC and BET Inhibitors.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Disruption of the interaction of bromo and extraterminal (BET) proteins with acetylated histones using small molecule inhibitors suppresses Myc-driven cancers and TLR-induced inflammation in mouse models. The predominant mechanism of BET inhibitor action is to suppress BET-mediated recruitment of positive transcription elongation factor b and, thus, transcription elongation. We investigated the effects of BET inhibitor I-BET151 on transcriptional responses to TLR4 and TNF in primary human monocytes and also on responses to cytokines IFN-β, IFN-γ, IL-4, and IL-10, which activate the JAK-STAT signaling pathway and are important for monocyte polarization and inflammatory diseases. I-BET151 suppressed TLR4- and TNF-induced IFN responses by diminishing both autocrine IFN-β expression and transcriptional responses to IFN-β. I-BET151 inhibited cytokine-induced transcription of STAT targets in a gene-specific manner without affecting STAT activation or recruitment. This inhibition was independent of Myc or other upstream activators. IFN-stimulated gene transcription is regulated primarily at the level of transcription initiation. Accordingly, we found that I-BET151 suppressed the recruitment of transcriptional machinery to the CXCL10 promoter and an upstream enhancer. Our findings suggest that BET inhibition reduces inflammation partially through suppressing cytokine activity and expands the understanding of the inhibitory and potentially selective immunosuppressive effects of inhibiting BET proteins.
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Registered trials
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.