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.

The Journal of Infection
|August 13, 2013
PubMed
Abstract

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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