ArticleThe Journal of biological chemistry2016
Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects.
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. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Integrated in vitro and multi-cohort cross-omics analysis of HTLV-1-associated lung pathology reveals a RelA-dependent mechanism for monocyte recruitment and differentiation.Molecular medicine (Cambridge, Mass.) · 2026Article
- Evolutionary Integration and Glucocorticoid Regulation of the Respiratory System: Structure, Function, and Homeostatic Adaptation.Medical sciences (Basel, Switzerland) · 2026Review
- Article
- Differential RELA and GR recruitment to the BIRC3/BIRC2 locus: Molecular insight as to combinatorial regulation by proinflammatory cytokines and glucocorticoid.Molecular pharmacology · 2025Article
- Enhancer RNA transcription pinpoints functional genetic variants linked to asthma.Nature communications · 2025Article
- Article
- TFscope: systematic analysis of the sequence features involved in the binding preferences of transcription factors.Genome biology · 2024Article
- Blood-derived lysophospholipid sustains hepatic phospholipids and fat storage necessary for hepatoprotection in overnutrition.The Journal of clinical investigation · 2023Article
- Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure.Antioxidants (Basel, Switzerland) · 2023Article
- Glucocorticoids and medroxyprogesterone acetate synergize with inflammatory stimuli to selectively upregulate CCL20 transcription.Molecular and cellular endocrinology · 2023Article
- Decreased ubiquitin modifying enzyme A20 associated with hyper-responsiveness to ovalbumin challenge following intrauterine growth restriction.Respiratory research · 2023Article
- Differential regulation of BIRC2 and BIRC3 expression by inflammatory cytokines and glucocorticoids in pulmonary epithelial cells.PloS one · 2023Article
- α1-Antitrypsin Binds to the Glucocorticoid Receptor with Anti-Inflammatory and Antimycobacterial Significance in Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Multiomics analysis identifies BIRC3 as a novel glucocorticoid response-associated gene.The Journal of allergy and clinical immunology · 2022Article
- Insights into glucocorticoid responses derived from omics studies.Pharmacology & therapeutics · 2021Review
- Pleiotropic Effects of Glucocorticoids on the Immune System in Circadian Rhythm and Stress.Frontiers in immunology · 2021Review
- Preventing the development of severe COVID-19 by modifying immunothrombosis.Life sciences · 2021Review
- Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19.Frontiers in pharmacology · 2021Article
- Article
- Important lessons learned from studies on the pharmacology of glucocorticoids in human airway smooth muscle cells: Too much of a good thing may be a problem.Pharmacology & therapeutics · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Antagonism of pro-inflammatory transcription factors by monomeric glucocorticoid receptor (GR) has long been viewed as central to glucocorticoid (GC) efficacy. However, the mechanisms and targets through which GCs exert therapeutic effects in diseases such as asthma remain incompletely understood. We previously defined a surprising cooperative interaction between GR and NF-κB that enhanced expression of A20 (TNFAIP3), a potent inhibitor of NF-κB. Here we extend this observation to establish that A20 is required for maximal cytokine repression by GCs. To ascertain the global extent of GR and NF-κB cooperation, we determined genome-wide occupancy of GR, the p65 subunit of NF-κB, and RNA polymerase II in airway epithelial cells treated with dexamethasone, TNF, or both using chromatin immunoprecipitation followed by deep sequencing. We found that GR recruits p65 to dimeric GR binding sites across the genome and discovered additional regulatory elements in which GR-p65 cooperation augments gene expression. GR targets regulated by this mechanism include key anti-inflammatory and injury response genes such as SERPINA1, which encodes α1 antitrypsin, and FOXP4, an inhibitor of mucus production. Although dexamethasone treatment reduced RNA polymerase II occupancy of TNF targets such as IL8 and TNFAIP2, we were unable to correlate specific binding sequences for GR or occupancy patterns with repressive effects on transcription. Our results suggest that cooperative anti-inflammatory gene regulation by GR and p65 contributes to GC efficacy, whereas tethering interactions between GR and p65 are not universally required for GC-based gene repression.
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