Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice.
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-kappa B in these cells. Thus, impaired nuclear translocation of GR and the lack of transcriptional suppression of NF-kappa B by GC were identified as the molecular mechanisms responsible for the observed GC resistance in spleens of socially stressed mice.
Quan
Ning
N
Section of Oral Biology, The Ohio State University Health Science Center, Institute for Behavioral Medicine Research and Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH 43210, USA. quan.14@osu.edu
Avitsur
Ronit
R
Stark
Jennifer L
JL
He
Lingli
L
Lai
Wenmin
W
Dhabhar
Firdaus
F
Sheridan
John F
JF
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology*; D004351:Drug Resistance / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism / Q000523:psychology
D008070:Lipopolysaccharides; D003345:Corticosterone