Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice

Ning Quan, Ronit Avitsur, Jennifer L. Stark, Lingli He, Wenmin Lai, Firdaus Dhabhar, John F. Sheridan

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Splenocytes from socially stressed male mice display functional glucocorticoid (GC) resistance, viz., the antiproliferative effects of GC on lipopolysaccharide (LPS)-stimulated splenocytes is absent. In this study, we investigated changes in the structure and function of the glucocorticoid receptor (GR) in socially stressed animals. Changes of GR at both DNA and RNA levels were excluded. Reduced GR function was restricted to macrophages (CD11b+) in association with impaired nuclear translocation of GR after GC stimulation. Consequently, GC failed to block the activation of NF-κB in these cells. Thus, impaired nuclear translocation of GR and the lack of transcriptional suppression of NF-κB by GC were identified as the molecular mechanisms responsible for the observed GC resistance in spleens of socially stressed mice.

Original languageEnglish (US)
Pages (from-to)51-58
Number of pages8
JournalJournal of Neuroimmunology
Volume137
Issue number1-2
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Glucocorticoid Receptors
Glucocorticoids
Lipopolysaccharides
Spleen
Macrophages
Glucocorticoid Receptor Deficiency
RNA
DNA

Keywords

  • GC resistance
  • Glucocorticoid receptor
  • GR nuclear translocation
  • NF-κB
  • Social stress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Cite this

Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice. / Quan, Ning; Avitsur, Ronit; Stark, Jennifer L.; He, Lingli; Lai, Wenmin; Dhabhar, Firdaus; Sheridan, John F.

In: Journal of Neuroimmunology, Vol. 137, No. 1-2, 01.01.2003, p. 51-58.

Research output: Contribution to journalArticle

Quan, Ning ; Avitsur, Ronit ; Stark, Jennifer L. ; He, Lingli ; Lai, Wenmin ; Dhabhar, Firdaus ; Sheridan, John F. / Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice. In: Journal of Neuroimmunology. 2003 ; Vol. 137, No. 1-2. pp. 51-58.
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