Glucocorticoids target suppressor of cytokine signaling 1 (SOCS1) and type 1 interferons to regulate Toll-like receptor-induced STAT1 activation
Open accessAbstract
Endogenous and pharmacologic glucocorticoids (GCs) limit inflammatory cascades initiated by Toll-like receptor (TLR) activation. A long-standing clinical observation has been the delay between GC administration and the manifestation of GC's anti-inflammatory actions. We hypothesized that the GCs would have inhibitory effects that target late temporal pathways that propagate proinflammatory signals. Here we interrogated signal transducer and activator of transcription 1 (STAT1) regulation by GC and its consequences for cytokine production during activation of macrophages with TLR-specific ligands. We found that robust STAT1 activation does not occur until 2-3 h after TLR engagement, and that GC suppression of STAT1 phosphorylation first manifests at this time. GC attenuates TLR4-mediated STAT1 activation only through induction of suppressor of cytokine signaling 1 (SOCS1), which increases throughout the 6-h period after treatment. Inhibition of TLR3-mediated STAT1 activation occurs via two mechanisms, impairment of type I IFN secretion and induction of SOCS1. Our data show that SOCS1 and type I interferons are critical GC targets for regulating STAT1 activity and may account for overall GC effectiveness in inflammation suppression in the clinically relevant time frame.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
GR-mediated transactivation typically induces expression of signaling inhibitors such as IκBα, MPK-1, IL-10, Annexin A1, GILZ, and SOCS proteins, which interfere with immune signaling pathways such as those triggered by Toll-like receptors.
“GR-mediated transactivation typically induces the expression of potent signaling inhibitors (e.g., IκBα, MPK-1, IL-10, Annexin A1, GILZ, and SOCS proteins), which strongly interfere with salient immune signaling pathways such as those triggered by the Toll-like receptors (TLR) (82–85).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [83]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 33 · Cited by 93
- Authors
- Bhattacharyya, S., Zhao, Y., Kay, T. W. H., & Muglia, L. J.
- Affiliations
- Vanderbilt University (US)
- St Vincents Institute of Medical Research (AU)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-05-23
- Volume
- 108
- Issue
- 23
- Pages
- 9554-9559
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3111275
- OpenAlex
- W1969006833
- Cited by
- 93
- References
- 33
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 1 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 3 · 2015: 8 · 2014: 7 · 2013: 7 · 2012: 15
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institutes of Health
- National Institute of Mental Health (MH79010, R01MH079010)
- National Institute of Allergy and Infectious Diseases (AI50653)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- glucocorticoids, SOCS1, type I interferon, STAT1 activation, Toll-like receptor signaling, TLR4, TLR3, macrophages, anti-inflammatory activity, STAT1 phosphorylation, cytokine production
- MeSH terms
- Suppressor of Cytokine Signaling 1 Protein, Animals, Cells, Cultured, Dexamethasone, Glucocorticoids, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Phosphorylation, Poly I-C, Blotting, Western, Interleukin-6, Interferon-alpha, Interferon-beta, Receptors, Interferon, Mice, Knockout, STAT1 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Interferon Regulatory Factor-3, Toll-Like Receptors, Mice, Janus Kinase 2, Interleukin-12 Subunit p40, Mice, 129 Strain
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
