ArticleProceedings of the National Academy of Sciences of the United States of America2019
TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. 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 40 papers.
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Who cites it
40 citing papers in PubMed, 79 citations in OpenAlex.
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- The roles, mechanisms, and therapeutic implications of glucocorticoids in glucose and lipid metabolism.Military Medical Research · 2026Review
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- Glucocorticoid-mediated suppression of the CCL2-CCR2 axis drives monocyte dysfunction in severe pneumonia among immunocompromised hosts.Respiratory research · 2025Article
- WTAP-mediated mScience China. Life sciences · 2025Article
- Leveraging a self-cleaving peptide for tailored control in proximity labeling proteomics.Cell reports methods · 2024Article
- The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.Endocrine reviews · 2024Review
- The Effect of Exposure to Neighborhood Violence on Glucocorticoid Receptor Signaling in Lung Tumors.Cancer research communications · 2024Article
- NCOR1/2 and glucocorticoid receptor orchestrate hepatic function.Nature metabolism · 2024Article
- Selective Modulation of the Human Glucocorticoid Receptor Compromises GR Chromatin Occupancy and Recruitment of p300/CBP and the Mediator Complex.Molecular & cellular proteomics : MCP · 2024Article
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Glucocorticoid receptor response and glucocorticoid-induced leucine zipper expression in neutrophils of critically ill patients with traumatic and non-traumatic brain injury.Frontiers in endocrinology · 2024Observational
- Skin Anti-Inflammatory Potential with Reduced Side Effects of Novel Glucocorticoid Receptor Agonists.International journal of molecular sciences · 2023Article
- Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators.Pharmacology & therapeutics · 2023Review
- Plasma proteome of Long-COVID patients indicates HIF-mediated vasculo-proliferative disease with impact on brain and heart function.Journal of translational medicine · 2023Article
- Sex-differences in anxiety, neuroinflammatory markers, and enhanced fear learning following chronic heroin withdrawal.Psychopharmacology · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoid resistance (GCR) is defined as an unresponsiveness to the therapeutic effects, including the antiinflammatory ones of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a problem in the management of inflammatory diseases and can be congenital as well as acquired. The strong proinflammatory cytokine TNF-alpha (TNF) induces an acute form of GCR, not only in mice, but also in several cell lines: e.g., in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-stimulated direct GR-dependent gene up- and down-regulation. We report that TNF has a significant and broad impact on this transcriptional performance of GR, but no impact on nuclear translocation, dimerization, or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome was strongly modulated by TNF. One GR cofactor that interacted significantly less with the receptor under GCR conditions is p300. NFκB activation and p300 knockdown both reduced direct transcriptional output of GR whereas p300 overexpression and NFκB inhibition reverted TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis was supported by FRET studies. This mechanism of GCR opens avenues for therapeutic interventions in GCR diseases.
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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.