Cited by 115Cytokine Signaling Pathways and InteractionsEstrogen and related hormone effectsReceptor Mechanisms and Signaling

A Role for STAT5 in the Pathogenesis of IL-2-Induced Glucocorticoid Resistance

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Goleva, Elena, Kisich, Kevin O, Leung, Donald Y M·2002·The Journal of Immunology

Abstract

Glucocorticoids (GC) are highly effective in the control of diseases associated with T cell activation. However, a subset of individuals is GC insensitive. Previous studies have demonstrated that IL-2 can induce steroid resistance in mouse T cells. However, the mechanism for this phenomenon is unknown. In the current study we found that the murine cell line (HT-2) is steroid resistant when incubated with IL-2, but steroid sensitive when grown in IL-4. Furthermore, when HT-2 cells are treated with IL-2, the glucocorticoid receptor (GCR) does not translocate to the cell nucleus after dexamethasone treatment. In contrast, the GCR in IL-4-stimulated HT-2 cells does translocate into the cell nucleus after dexamethasone treatment. IL-2-induced steroid insensitivity in HT-2 cells appears to be a signaling event as the effects of IL-2 on nuclear translocation of the GCR occurred within 30 min even in the presence of cycloheximide. Indeed, preincubation of HT-2 cells with a Janus-associated kinase 3 inhibitor restored nuclear translocation of the GCR even in the presence of IL-2. Immunoprecipitation experiments revealed that phosphorylated STAT5 and GCR formed immune complexes. This association may lead to retardation of GCR nuclear translocation because IL-2 was not able to induce steroid insensitivity in splenocytes from STAT5 knockout mice. This study demonstrates a novel role for STAT5 in IL-2-induced steroid insensitivity.

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Crossref · 10.4049/jimmunol.169.10.5934

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  • Inhibition of prednisolone-induced GR translocation, as well as GR-mediated gene transcription in human epidermal cells by TNF-α, is dependent on ERK activation.

    “inhibition of prednisolone-induced GR translocation, as well as GR-mediated gene transcription in human epidermal cells by TNF-α, is dependent on ERK activation.46”

    From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [46]

    The Discussion and the section on JAK3 inhibition describe IL-2-induced glucocorticoid resistance in T cells, involving STAT5, JAK3 and p38 MAPK. Searches for TNF-α, ERK, prednisolone and human epidermal cells found no passage addressing the claimed mechanism; the paper’s findings do not establish or contradict it. (LLM, conf=0.76)

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Authors
Goleva, E., Kisich, K. O., & Leung, D. Y. M.
Affiliations
National Jewish Health (US)
Corresponding author
Goleva, Elena
Venue
The Journal of Immunology
Published
2002-11
Volume
169
Issue
10
Pages
5934-5940
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2171016604
Cited by
113
References
37
Citations by year
2026: 3 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 8 · 2014: 3 · 2013: 7 · 2012: 5
FWCI
2.22
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (HL37260, RR00051)
  • National Heart, Lung, and Blood Institute (HL 36577, P01HL036577, HL 37260)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 41256, R01AR041256)
  • National Center for Research Resources (RR-00051)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
STAT5, glucocorticoid resistance, interleukin-2, glucocorticoid receptor, nuclear translocation, dexamethasone, IL-4, T cell activation, immune complex formation
MeSH terms
Animals, Cell Division, Cell Line, Cell Nucleus, Cells, Cultured, Dexamethasone, DNA-Binding Proteins, Drug Resistance, Enzyme Inhibitors, Interleukin-2, Mice, Inbred C57BL, Milk Proteins, Protein-Tyrosine Kinases, Receptors, Glucocorticoid, Spleen, T-Lymphocytes, Signal Transduction, Trans-Activators, Mice, Knockout, Dimerization, Active Transport, Cell Nucleus, STAT5 Transcription Factor, Mice, Janus Kinase 3

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