ArticleThe Journal of biological chemistry2011
Glucocorticoid-independent repression of tumor necrosis factor (TNF) alpha-stimulated interleukin (IL)-6 expression by the glucocorticoid receptor: a potential mechanism for protection against an excessive inflammatory response.
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 33 papers.
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Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Dexmedetomidine Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting MDH2 Lactylation via Regulating Metabolic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases.Signal transduction and targeted therapy · 2023Article
- Group 3 innate lymphoid cells secret neutrophil chemoattractants and are insensitive to glucocorticoid via aberrant GR phosphorylation.Respiratory research · 2023Article
- Mechanisms behind context-dependent role of glucocorticoids in breast cancer progression.Cancer metastasis reviews · 2022Review
- The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia.Frontiers in immunology · 2022Review
- GR-mediated transcriptional regulation of mJournal of animal science and biotechnology · 2021Article
- Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior.Molecular psychiatry · 2021Article
- Reciprocal Modulation of Antiretroviral Drug and Steroid Receptor FunctionAntimicrobial agents and chemotherapy · 2019Article
- Cytokine production in thyroid eye disease: in vitro effects of dexamethasone and IL-6 blockade with tocilizumab.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2019Article
- The contraceptive medroxyprogesterone acetate, unlike norethisterone, directly increases R5 HIV-1 infection in human cervical explant tissue at physiologically relevant concentrations.Scientific reports · 2019Article
- Article
- Article
- Combination of cationic dexamethasone derivative and STAT3 inhibitor (WP1066) for aggressive melanoma: a strategy for repurposing a phase I clinical trial drug.Molecular and cellular biochemistry · 2017Article
- New Insights in Glucocorticoid Receptor Signaling-More Than Just a Ligand-Binding Receptor.Frontiers in endocrinology · 2017Review
- Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy.Pharmacology & therapeutics · 2016Review
- The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling.Science translational medicine · 2016Article
- Induction of interferon-λ contributes to TLR3 and RIG-I activation-mediated inhibition of herpes simplex virus type 2 replication in human cervical epithelial cells.Molecular human reproduction · 2015Article
- Dexamethasone attenuates the embryotoxic effect of endometriotic peritoneal fluid in a murine model.Journal of assisted reproduction and genetics · 2015Article
- Minireview: Tipping the balance: ligand-independent activation of steroid receptors.Molecular endocrinology (Baltimore, Md.) · 2015Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TNFα signaling and cytokine levels play a crucial role in cervical immunity and the host response to infections. We investigated the role of liganded and unliganded glucocorticoid receptor (GR) in IL-6 and IL-8 gene regulation in response to TNFα in the End1/E6E7 immortalized human endocervical epithelial cell line. In the absence of glucocorticoids, both decreasing GR protein levels by an siRNA strategy and results with the GR antagonist RU486 suggest a role for the unliganded GR in reduction of TNFα-induced IL-6 and IL-8 mRNA levels in End1/E6E7 cells. Moreover, GR-dependent repression of endogenous IL-6 mRNA as well as a minimal IL-6 promoter-reporter gene is also demonstrated in COS-1 cells in the absence of GR ligand, suggesting a transcriptional mechanism that is not cell-specific. TNFα induced recruitment of both the unliganded GR and GR-interacting protein type 1 (GRIP-1) to the IL-6 promoter. This, together with GRIP-1 overexpression studies, suggests a function for GRIP-1 as a GR co-repressor in this context. TNFα was shown to induce phosphorylation of the unliganded human GR at Ser-226 but not Ser-211, unlike dexamethasone, which induced hyperphosphorylation at both serine residues. Ser-226 is shown to be required for the ligand-independent GR-mediated repression of IL-6 in response to TNFα. Taken together, these results support a model whereby the unliganded GR attenuates TNFα-stimulated IL-6 transcription by a mechanism involving selective phosphorylation and recruitment of the unliganded GR and GRIP-1 to the IL-6 promoter. These findings suggest the presence of a novel autoregulatory mechanism that may prevent overproduction of IL-6 in the endocervix, possibly protecting against negative effects of excessive inflammation.
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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.