ArticleThe Journal of biological chemistry2011
Tumor necrosis factor inhibits glucocorticoid receptor function in mice: a strong signal toward lethal shock.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review.International journal of molecular sciences · 2016Pooled it
- Glucocorticoid-mediated suppression of the CCL2-CCR2 axis drives monocyte dysfunction in severe pneumonia among immunocompromised hosts.Respiratory research · 2025Article
- Dietary bile acids alleviate corticosterone-induced fatty liver and hepatic glucocorticoid receptor suppression in broiler chickens.Journal of animal science · 2024Article
- The impact of hepatocyte-specific deletion of hypoxia-inducible factors on the development of polymicrobial sepsis with focus on GR and PPARα function.Frontiers in immunology · 2023Article
- Renaissance of glucocorticoids in critical care in the era of COVID-19: ten urging questions.Critical care (London, England) · 2022Review
- Narrative Review: Glucocorticoids in Alcoholic Hepatitis-Benefits, Side Effects, and Mechanisms.Journal of xenobiotics · 2022Review
- Dimerization of the Glucocorticoid Receptor and Its Importance in (Patho)physiology: A Primer.Cells · 2022Review
- Reprogramming of glucocorticoid receptor function by hypoxia.EMBO reports · 2022Article
- New insights into the cell- and tissue-specificity of glucocorticoid actions.Cellular & molecular immunology · 2021Review
- Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.EMBO molecular medicine · 2020Article
- Glucocorticoids limit lipopolysaccharide-induced lethal inflammation by a double control system.EMBO reports · 2020Article
- Sepsis therapies: learning from 30 years of failure of translational research to propose new leads.EMBO molecular medicine · 2020Review
- NF-κB c-Rel Dictates the Inflammatory Threshold by Acting as a Transcriptional Repressor.iScience · 2020Article
- Glucocorticoids in Sepsis: To Be or Not to Be.Frontiers in immunology · 2020Review
- TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Is AD a Stress-Related Disorder? Focus on the HPA Axis and Its Promising Therapeutic Targets.Frontiers in aging neuroscience · 2019Article
- A General Introduction to Glucocorticoid Biology.Frontiers in immunology · 2019Review
- A screening assay for Selective Dimerizing Glucocorticoid Receptor Agonists and Modulators (SEDIGRAM) that are effective against acute inflammation.Scientific reports · 2018Article
- HIV Neuroinfection and Alzheimer's Disease: Similarities and Potential Links?Frontiers in cellular neuroscience · 2018Article
- Immune Effects of Corticosteroids in Sepsis.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As glucocorticoid resistance (GCR) and the concomitant burden pose a worldwide problem, there is an urgent need for a more effective glucocorticoid therapy, for which insights into the molecular mechanisms of GCR are essential. In this study, we addressed the hypothesis that TNFα, a strong pro-inflammatory mediator in numerous inflammatory diseases, compromises the protective function of the glucocorticoid receptor (GR) against TNFα-induced lethal inflammation. Indeed, protection of mice by dexamethasone against TNFα lethality was completely abolished when it was administered after TNFα stimulation, indicating compromised GR function upon TNFα challenge. TNFα-induced GCR was further demonstrated by impaired GR-dependent gene expression in the liver. Furthermore, TNFα down-regulates the levels of both GR mRNA and protein. However, this down-regulation seems to occur independently of GC production, as TNFα also resulted in down-regulation of GR levels in adrenalectomized mice. These findings suggest that the decreased amount of GR determines the GR response and outcome of TNFα-induced shock, as supported by our studies with GR heterozygous mice. We propose that by inducing GCR, TNFα inhibits a major brake on inflammation and thereby amplifies the pro-inflammatory response. Our findings might prove helpful in understanding GCR in inflammatory diseases in which TNFα is intimately involved.
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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.