ArticleBritish journal of pharmacology2012
Anti-inflammatory effects of selective glucocorticoid receptor modulators are partially dependent on up-regulation of dual specificity phosphatase 1.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Relationship Between Glucocorticoids and Insulin Resistance in Healthy Individuals.Medical science monitor : international medical journal of experimental and clinical research · 2016Pooled it
- Cell-specific expression and signaling of glucocorticoid receptor isoforms over time in critically ill patients with a low inflammatory response.Critical care (London, England) · 2025Observational
- Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?Endocrine reviews · 2023Review
- Article
- Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β.Frontiers in immunology · 2023Article
- Caveolin1 interacts with the glucocorticoid receptor in the lung but is dispensable for its anti-inflammatory actions in lung inflammation and Trichuris Muris infection.Scientific reports · 2019Article
- Cdk5 Deletion Enhances the Anti-inflammatory Potential of GC-Mediated GR Activation During Inflammation.Frontiers in immunology · 2019Article
- A screening assay for Selective Dimerizing Glucocorticoid Receptor Agonists and Modulators (SEDIGRAM) that are effective against acute inflammation.Scientific reports · 2018Article
- Mineralocorticoid Antagonist Improves Glucocorticoid Receptor Signaling and Dexamethasone Analgesia in an Animal Model of Low Back Pain.Frontiers in cellular neuroscience · 2018Article
- Glucocorticoid receptors: finding the middle ground.The Journal of clinical investigation · 2017Review
- Safer topical treatment for inflammation using 5α-tetrahydrocorticosterone in mouse models.Biochemical pharmacology · 2017Article
- The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases.Biochemical Society transactions · 2016Review
- A steroid-mimicking nanomaterial that mediates inhibition of human lung mast cell responses.Nanomedicine : nanotechnology, biology, and medicine · 2014Article
- SOD therapeutics: latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways.Antioxidants & redox signaling · 2014Review
- Roles for the mitogen-activated protein kinase (MAPK) phosphatase, DUSP1, in feedback control of inflammatory gene expression and repression by dexamethasone.The Journal of biological chemistry · 2014Article
- Context-dependent cooperation between nuclear factor κB (NF-κB) and the glucocorticoid receptor at a TNFAIP3 intronic enhancer: a mechanism to maintain negative feedback control of inflammation.The Journal of biological chemistry · 2014Article
- Discovery of GW870086: a potent anti-inflammatory steroid with a unique pharmacological profile.British journal of pharmacology · 2013Article
- The multiple facets of glucocorticoid action in rheumatoid arthritis.Nature reviews. Rheumatology · 2012Review
- Anti-inflammatory effects of mapracorat, a novel selective glucocorticoid receptor agonist, is partially mediated by MAP kinase phosphatase-1 (MKP-1).The Journal of biological chemistry · 2012Article
- Corticosteroids and β₂-agonists upregulate mitogen-activated protein kinase phosphatase 1: in vitro mechanisms.British journal of pharmacology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
background and purposeIt is thought that the anti-inflammatory effects of glucocorticoids (GCs) are largely due to GC receptor (GR)-mediated transrepression of NF-κB and other transcription factors, whereas side effects are caused by activation of gene expression (transactivation). Selective GR modulators (SGRMs) that preferentially promote transrepression should retain anti-inflammatory properties whilst causing fewer side effects. Contradicting this model, we found that anti-inflammatory effects of the classical GC dexamethasone were partly dependent on transactivation of the dual specificity phosphatase 1 (DUSP1) gene. We wished to determine whether anti-inflammatory effects of SGRMs are also mediated by DUSP1. EXPERIMENTAL APPROACH: Dissociated properties of two SGRMs were confirmed using GR- and NF-κB-dependent reporters, and capacity to activate GC-responsive elements of the DUSP1 gene was tested. Effects of SGRMs on the expression of DUSP1 and pro-inflammatory gene products were assessed in various cell lines and in primary murine Dusp1(+/+) and Dusp1(-/-) macrophages. KEY
resultsThe SGRMs were able to up-regulate DUSP1 in several cell types, and this response correlated with the ability of the compounds to suppress COX-2 expression. Several anti-inflammatory effects of SGRMs were ablated or significantly impaired in Dusp1(-/-) macrophages. CONCLUSIONS AND IMPLICATIONS: Like dexamethasone, SGRMs appear to exert anti-inflammatory effects partly via the up-regulation of DUSP1. This finding has implications for how potentially therapeutic novel GR ligands are identified and assessed.
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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.