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

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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

DOI 10.4049/jimmunol.169.10.5934

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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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Authors: Goleva, E., Kisich, K. O., & Leung, D. Y. M.
Affiliations: National Jewish Health (US)
Corresponding author: Goleva, Elena
ORCID: Goleva, Elena
Leung, Donald Y M
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2002-11
Volume: 169
Issue: 10
Pages: 5934-5940
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.169.10.5934
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: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
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: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › 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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A Role for STAT5 in the Pathogenesis of IL-2-Induced Glucocorticoid Resistance

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