Expression of glucocorticoid resistance following social stress requires a second signal

Ronit Avitsur, David A. Padgett, Firdaus S. Dhabhar, Jennifer L. Stark, Kari A. Kramer, Harald Engler, John F. Sheridan

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Stimulation of splenocytes from socially stressed mice [social disruption (SDR)] with Gram-negative bacterial lipopolysaccharide (LPS) revealed a state of functional glucocorticoid (GC) resistance. LPS-stimulated splenocytes were less sensitive to the inhibitory effects of corticosterone. This study demonstrated that activation signals were required for the expression of splenic GC resistance. The results demonstrated that six cycles of SDR induced splenomegaly and increased the number of CD11b-positive monocytes. SDR also increased the viability of cultured, nonstimulated splenocytes, and addition of corticosterone reduced the viability of these cells in a dose-dependent manner. However, following stimulation with LPS, the sensitivity of SDR splenocytes to GC was reduced. Similar results were obtained using lipid A, a fraction of the LPS molecule that binds to Toll-like receptor (TLR)4. Furthermore, C3H/HeJ mice that do not possess a functional TLR4 molecule responded to SDR with an increased number of CD11b-positive monocytes in the spleen and increased viability of nonstimulated splenocytes. However, neither LPS nor lipid A stimulation resulted in the expression of GC resistance. Together, these findings suggest that the expression of GC resistance in response to SDR requires a second signal that can be provided by ligation of TLR4.

Original languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalJournal of Leukocyte Biology
Volume74
Issue number4
DOIs
StatePublished - Oct 2003

Keywords

  • C3H/Hej
  • CD11b
  • Lipopolysaccharide
  • Monocytes/macrophages
  • Social disruption (SDR)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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  • Cite this

    Avitsur, R., Padgett, D. A., Dhabhar, F. S., Stark, J. L., Kramer, K. A., Engler, H., & Sheridan, J. F. (2003). Expression of glucocorticoid resistance following social stress requires a second signal. Journal of Leukocyte Biology, 74(4), 507-513. https://doi.org/10.1189/jlb.0303090