Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis
Abstract
Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents. They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function, but the mechanism underlying this activity has been unclear. Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B (NF-κB) activation in mice and cultured cells. This inhibition is mediated by induction of the IκBα inhibitory protein, which traps activated NF-κB in inactive cytoplasmic complexes. Because NF-κB activates many immunoregulatory genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids.
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Glucocorticoids tend to confer protective, anti-inflammatory effects.
“as GCs tend to confer protective, anti-inflammatory effects.36,41–43”
From Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases (2015) · cites this paper as [42]
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- Authors
- Auphan, N., DiDonato, J. A., Rosette, C., Helmberg, A., & Karin, M.
- Affiliations
- Department of Pharmacology, Program in Biomedical Sciences, Center for Molecular Genetics, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0636, USA.
- University of California San Diego (US)
- Corresponding author
- DiDonato, Joseph A.
- Rosette, Caridad
- Karin, Michael
- Venue
- Science
- Published
- 1995-10-13
- Volume
- 270
- Issue
- 5234
- Pages
- 286-290
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1522773084
- Cited by
- 2,390
- References
- 53
- Citations by year
- 2026: 33 · 2025: 32 · 2024: 32 · 2023: 44 · 2022: 45 · 2021: 45 · 2020: 50 · 2019: 32 · 2018: 42 · 2017: 42 · 2016: 52 · 2015: 42 · 2014: 50 · 2013: 51 · 2012: 58
- FWCI
- 62.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- glucocorticoids, immunosuppression, NF-κB, IκBα, anti-inflammatory activity, cytokine production, immune function, pro-inflammatory stimuli, immunoregulatory genes
- MeSH terms
- NF-KappaB Inhibitor alpha, Animals, Anti-Inflammatory Agents, Cell Line, Cell Nucleus, Cytoplasm, Dexamethasone, DNA-Binding Proteins, Humans, Hybridomas, Immunosuppression Therapy, Interleukin-2, Lymph Nodes, Receptors, Glucocorticoid, T-Lymphocytes, Tetradecanoylphorbol Acetate, Tumor Cells, Cultured, NF-kappa B, Transcription Factor AP-1, I-kappa B Proteins, Mice, Transcription Factor RelA
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