Cited by 152Sepsis Diagnosis and TreatmentAdrenal Hormones and DisordersEstrogen and related hormone effects

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Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin‐1 in macrophages

Kleiman, Anna, Hübner, Sabine, Parkitna, Jan M. Rodriguez, Neumann, Anita, Hofer, Stefan, Weigand, Markus A., Bauer, Michael, Schmid, Wolfgang, Schütz, Gunter, Libert, Claude, Reichardt, Holger M., Tuckermann, Jan P.·2012·The FASEB Journal

DOI 10.1096/fj.11-192112

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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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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: Kleiman, Anna
Parkitna, Jan M. Rodriguez
Hofer, Stefan
Bauer, Michael
Libert, Claude
Reichardt, Holger M.
Tuckermann, Jan P.
Venue: The FASEB Journal
Publisher: Wiley
Published: 2011-10-31
Volume: 26
Issue: 2
Pages: 722-729
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.11-192112
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin‐1 in macrophages

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