ArticlePloS one
Bromodomain and Extra Terminal (BET) Inhibitor Suppresses Macrophage-Driven Steroid-Resistant Exacerbations of Airway Hyper-Responsiveness and Inflammation.
Article in PloS one. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
11 citing papers in PubMed, 23 citations in OpenAlex.
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Structure-Guided Design of a Domain-Selective Bromodomain and Extra Terminal N-Terminal Bromodomain Chemical Probe.Journal of medicinal chemistry · 2023Article
- Advances in respiratory physiology in mouse models of experimental asthma.Frontiers in physiology · 2023Review
- Inhibition of BET Family Proteins Suppresses African Swine Fever Virus Infection.Microbiology spectrum · 2022Article
- Different Phenotypes in Asthma: Clinical Findings and Experimental Animal Models.Clinical reviews in allergy & immunology · 2022Review
- Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?Viruses · 2021Review
- Phase 1 Study of Molibresib (GSK525762), a Bromodomain and Extra-Terminal Domain Protein Inhibitor, in NUT Carcinoma and Other Solid Tumors.JNCI cancer spectrum · 2020Article
- Epigenetic regulation of macrophages: from homeostasis maintenance to host defense.Cellular & molecular immunology · 2020Review
- Epigenetics and Trained Immunity.Antioxidants & redox signaling · 2018Review
- Modeling TImmunological reviews · 2017Review
- Steroid resistance and concomitant respiratory infections: A challenging battle in pulmonary clinic.EXCLI journal · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExacerbations of asthma are linked to significant decline in lung function and are often poorly controlled by corticosteroid treatment. Clinical investigations indicate that viral and bacterial infections play crucial roles in the onset of steroid-resistant inflammation and airways hyperresponsiveness (AHR) that are hallmark features of exacerbations. We have previously shown that interferon γ (IFNγ) and lipopolysaccharide (LPS) cooperatively activate pulmonary macrophages and induce steroid-resistant airway inflammation and AHR in mouse models. Furthermore, we have established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation of asthma, which exhibits macrophage-dependent, steroid-resistant lung disease. Emerging evidence has demonstrated a key role for bromo- and extra-terminal (BET) proteins in the regulation of inflammatory gene expression in macrophages. We hypothesised that BET proteins may be involved in the regulation of AHR and airway inflammation in our steroid-resistant exacerbation models. METHODOLOGY/PRINCIPAL
findingsWe investigated the effects of a BET inhibitor (I-BET-762) on the development of steroid-resistant AHR and airway inflammation in two mouse models. I-BET-762 administration decreased macrophage and neutrophil infiltration into the airways, and suppressed key inflammatory cytokines in both models. I-BET treatment also suppressed key inflammatory cytokines linked to the development of steroid-resistant inflammation such as monocyte chemoattractant protein 1 (MCP-1), keratinocyte-derived protein chemokine (KC), IFNγ, and interleukin 27 (IL-27). Attenuation of inflammation was associated with suppression of AHR. CONCLUSIONS/SIGNIFICANCE: Our results suggest that BET proteins play an important role in the regulation of steroid-resistant exacerbations of airway inflammation and AHR. BET proteins may be potential targets for the development of future therapies to treat steroid-resistant inflammatory components of asthma.
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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.