Cited by 81Stress Responses and CortisolImmune Response and InflammationAdrenal Hormones and Disorders

Expression of glucocorticoid resistance following social stress requires a second signal

Avitsur, Ronit, Padgett, David A, Dhabhar, Firdaus S, Stark, Jennifer L, Kramer, Kari A, Engler, Harald, Sheridan, John F·2003·Journal of Leukocyte Biology

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.

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Crossref · 10.1189/jlb.0303090

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  • Newly differentiated Ly6c hi monocytes express surface activation markers that enhance immune function, including TLRs, CCR2, and co-stimulator receptors, which are upregulated by RSD.

    “For example, surface activation markers including Toll-like receptors (TLRs), chemotactic receptors including CCR2, and co-stimulator receptors are upregulated by RSD (Avitsur et al, 2003;Engler et al, 2004;Bailey et al, 2007;Powell et al, 2009;Hanke et al, 2012).”

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Authors
Avitsur, R., Padgett, D. A., Dhabhar, F. S., Stark, J. L., Kramer, K. A., Engler, H., & Sheridan, J. F.
Affiliations
The Ohio State University (US)
Corresponding author
Sheridan, John F
Venue
Journal of Leukocyte Biology
Published
2003-07-15
Volume
74
Issue
4
Pages
507-513
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
OpenAlex
W2082793851
Cited by
81
References
25
Citations by year
2026: 2 · 2024: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2018: 4 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 2 · 2013: 5 · 2012: 6
FWCI
1.01
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Leukocyte Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
NIH (MH46801-08, DE13749-01, RO148995)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
glucocorticoid resistance, social stress, social disruption, lipopolysaccharide, lipid A, TLR4, splenocytes, corticosterone, splenomegaly, C3H/HeJ mice, second signal
MeSH terms
Animals, Corticosterone, Dose-Response Relationship, Drug, Drug Resistance, Leukocyte Count, Lipid A, Lipopolysaccharides, Male, Membrane Glycoproteins, Mice, Inbred C3H, Mice, Inbred C57BL, Receptors, Cell Surface, Splenomegaly, Stress, Psychological, Signal Transduction, Toll-Like Receptors, Toll-Like Receptor 4, Mice

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