The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin‐1 in macrophages
Abstract
ABSTRACT Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization‐deficient GR (GR dim ) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)‐induced septic shock. TNF‐α is normally regulated in these mice, but down‐regulation of IL‐6 and IL‐1β is diminished. LPS‐treated macrophages derived from GR dim mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL‐1 receptor antagonist improved survival of GR dim mice and mice lacking the GR in macrophages (GR LysMCre ) mice. This suggests that regulation of IL‐1β in macrophages by GCs is pivotal to control sepsis.—Kleiman, A., Hübner, S., Rodriguez Parkitna, J. M., Neumann, A., Hofer, S., Weigand, M. A., Bauer, M., Schmid, W., Schütz, G., Libert, C., Reichardt, H. M., Tuckermann, J. P. Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin‐1 in macrophages. FASEB J. 26, 722–729 (2012). www.fasebj.org
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“This hypothesis is supported by prior work showing that repression of IL-1β, MIP-2, MCP-1, and IP-10 by GCs is hindered in macrophages isolated from GRdim mice (109, 110).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [109]
In the citing paper
“Of particular note, increased mortality was also observed in GRlysMCre mice compared to controls following a peripheral injection of LPS (109).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [109]
Citations
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Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
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“sequences of hormone-responsive target genes (8).”
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Metadata
- Authors
- Kleiman, A., Hübner, S., Parkitna, J. M. R., Neumann, A., Hofer, S., Weigand, M. A., Bauer, M., Schmid, W., Schütz, G., Libert, C., Reichardt, H. M., & Tuckermann, J. P.
- Affiliations
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- Justus-Liebig-Universität Gießen (DE)
- Jena University Hospital (DE)
- Vlaams Instituut voor Biotechnologie (BE)
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Tuckermann, Jan P.
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2011-10-31
- Volume
- 26
- Issue
- 2
- Pages
- 722-729
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2066022850
- Cited by
- 152
- References
- 33
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 14 · 2019: 16 · 2018: 16 · 2017: 16 · 2016: 10 · 2015: 14 · 2014: 10 · 2013: 8 · 2012: 7
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- GRO (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Tu220/3, Re1631/7-1)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- glucocorticoid receptor, receptor dimerization, septic shock, sepsis, IL-1β, macrophages, lipopolysaccharide, cecal ligation and puncture, interleukin-6, TNF-α, interleukin-1 receptor antagonist, glucocorticoid resistance, endogenous glucocorticoids
- MeSH terms
- Animals, Dexamethasone, Disease Models, Animal, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Receptors, Glucocorticoid, RNA, RNA, Messenger, Shock, Septic, Tumor Necrosis Factor-alpha, Signal Transduction, Down-Regulation, Interleukin-6, Receptors, Interleukin-1, Dimerization, Protein Structure, Quaternary, Mice, Interleukin-1beta, Mice, 129 Strain, Transcriptome
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