Cited by 2,390NF-κB Signaling PathwaysSignaling Pathways in DiseaseImmune Response and Inflammation

Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis

Auphan, Nathalie, DiDonato, Joseph A., Rosette, Caridad, Helmberg, Arno, Karin, Michael·1995·Science

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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Crossref · 10.1126/science.270.5234.286

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53 of 53 references verified0 citation errors · 0 not checkable

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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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