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Updated: May 9, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis
Maria Bergquist1, Merja Nurkkala, Christian Rylander
1Department of Medical Sciences, The Hedenstierna Laboratory, Uppsala University, Sweden; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.
Introduction:
Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesized that failure to respond to steroid therapy may be caused by decreased expression and/or function of glucocorticoid receptors (GR) and studied this in a mouse model of Staphylococcus aureus sepsis. The impact of timing of dexamethasone treatment was also investigated.
Methods:
Male C57BL/6J mice were intravenously inoculated with S. aureus and GR expression and binding ability in blood, spleen and lymph nodes were analysed by means of flow cytometry. GR translocation was analysed using Image Stream. Septic mice were administered dexamethasone at 22, 26, 48, 72 and 96 h after inoculation and body weight, as a sign of dehydration, was observed.
Results:
GR expression was decreased in septic animals, but not the ligand binding capacity. GR translocation was decreased in septic mice compared to control animals. Early dexamethasone treatment (22 and 26 h) improved clinical outcome as studied by weight gain compared to when treatment was started at later time points (48, 72 and 96 h).
Conclusion:
Our data provide evidence that GR expression is progressively decreased in experimental sepsis and that dexamethasone has a decreased ability to translocate into the cell nucleus. This may explain why steroid treatment is only beneficial when administered early in sepsis and septic shock.
Insights
Decreased glucocorticoid receptor (GR) expression in sepsis impairs dexamethasone effectiveness. Early GR-targeted steroid treatment in Staphylococcus aureus sepsis improves outcomes, highlighting the critical role of timing.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Glucocorticoid therapy for septic shock is controversial.
- Steroid unresponsiveness may stem from impaired glucocorticoid receptor (GR) function.
- Investigated GR expression and function in a mouse model of Staphylococcus aureus sepsis.
Purpose of the Study:
- To investigate the role of glucocorticoid receptor (GR) expression and function in experimental sepsis.
- To determine the impact of dexamethasone treatment timing on sepsis outcomes.
Main Methods:
- Utilized a mouse model of Staphylococcus aureus sepsis.
- Analyzed GR expression, binding, and translocation using flow cytometry and Image Stream.
- Administered dexamethasone at various time points post-inoculation and monitored weight gain.
Main Results:
- Septic mice exhibited decreased GR expression and impaired GR nuclear translocation.
- Dexamethasone ligand binding capacity remained unaffected.
- Early dexamethasone administration (22 and 26 hours) improved weight gain compared to later treatments.
Conclusions:
- Experimental sepsis leads to reduced GR expression and impaired dexamethasone translocation.
- This dysfunction may explain the limited efficacy of late-stage steroid treatment in sepsis.
- Early intervention with dexamethasone is crucial for improved clinical outcomes in sepsis.
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