ArticleThe Journal of biological chemistry2010
Increased glucocorticoid receptor expression and activity mediate the LPS resistance of SPRET/EI mice.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Modulation of glucocorticoid receptor function under iron overload.Frontiers in immunology · 2025Article
- Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells.Frontiers in immunology · 2025Article
- Reprogramming of glucocorticoid receptor function by hypoxia.EMBO reports · 2022Article
- Glucocorticoid receptor hypersensitivity enhances inflammatory signaling and inhibits cell cycle progression in porcine PBMCs.Frontiers in immunology · 2022Article
- Neuroimmune Regulation in Sepsis-Associated Encephalopathy: The Interaction Between the Brain and Peripheral Immunity.Frontiers in neurology · 2022Review
- Circadian Rhythms in Bacterial Sepsis Pathology: What We Know and What We Should Know.Frontiers in cellular and infection microbiology · 2021Review
- Stress Response Simulated by Continuous Injection of ACTH Attenuates Lipopolysaccharide-Induced Inflammation in Porcine Adrenal Gland.Frontiers in veterinary science · 2020Article
- General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections.Frontiers in endocrinology · 2020Review
- Glucocorticoids in Sepsis: To Be or Not to Be.Frontiers in immunology · 2020Review
- Using the inbred mouse strain SPRET/EiJ to provide novel insights in inflammation and infection research.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- Comparing expression and activity of PCSK9 in SPRET/EiJ and C57BL/6J mouse strains shows lack of correlation with plasma cholesterol.Molecular genetics and metabolism reports · 2017Article
- Predicting RTS,S Vaccine-Mediated Protection from Transcriptomes in a Malaria-Challenge Clinical Trial.Frontiers in immunology · 2017Article
- Glucocorticoid-induced microRNA-511 protects against TNF by down-regulating TNFR1.EMBO molecular medicine · 2015Article
- Glucocorticoid Receptor Expression in Peripheral WBCs of Critically Ill Children.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2015Article
- Determining differentially expressed miRNAs and validating miRNA--target relationships using the SPRET/Ei mouse strain.Mammalian genome : official journal of the International Mammalian Genome Society · 2015Article
- Cross-talk between HPA-axis-increased glucocorticoids and mitochondrial stress determines immune responses and clinical manifestations of patients with sepsis.Redox report : communications in free radical research · 2015Review
- LPS resistance of SPRET/Ei mice is mediated by Gilz, encoded by the Tsc22d3 gene on the X chromosome.EMBO molecular medicine · 2013Article
- Tumor necrosis factor inhibits glucocorticoid receptor function in mice: a strong signal toward lethal shock.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SPRET/Ei mice are extremely resistant to acute LPS-induced lethal inflammation when compared with C57BL/6. We found that in vivo SPRET/Ei mice exhibit strongly reduced expression levels of cytokines and chemokines. To investigate the role of the potent anti-inflammatory glucocorticoid receptor (GR) in the SPRET/Ei phenotype, mice were treated with the GR antagonist RU486 or bilateral adrenalectomy. Under such conditions, both C57BL/6 and SPRET/Ei mice were strongly sensitized to LPS, and the differences in LPS response between SPRET/Ei and C57BL/6 mice were completely gone. These results underscore the central role of GR in the LPS hyporesponsiveness of SPRET/Ei mice. Compared with C57BL/6, SPRET/Ei mice were found to express higher GR levels, which were reflected in increased GR transactivation. Using a backcross mapping strategy, we demonstrate that the high GR transcription levels are linked to the Nr3c1 (GR) locus on chromosome 18 itself. Unexpectedly, SPRET/Ei mice exhibit a basal overactivation of the hypothalamic-pituitary-adrenal axis, namely strongly increased corticosterone levels, ACTH levels, and adrenocortical size. As a consequence of the excess of circulating glucocorticoids (GCs), levels of hepatic gluconeogenic enzymes are increased, and insulin secretion from pancreatic β-cells is impaired, both of which result in hyperglycemia and glucose intolerance in SPRET/Ei mice. We conclude that SPRET/Ei mice are unique as they display an unusual combination of elevated GR expression and increased endogenous GC levels. Hence, these mice provide a new and powerful tool for the study of GR- and GC-mediated mechanisms, including immune repressive functions, neuroendocrine regulation, insulin secretion, and carbohydrate metabolism.
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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.