Evidence map›Paper›PMID 10958685›Full record

ArticleMolecular and cellular biology2000

Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12.

K Ito, P J Barnes, I M Adcock

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01787097 (GR Activity in Induced Sputum Macrophages, and a Change in Inflammatory Biomarkers 2-hours After a Single Dose of Either Symbicort®/Budesonide/Formoterol or in Chronic Obstructive Pulmonary Disease), which is not on this map. Cited by 205 papers.

0numbers the graph read from it
0cells of the map it votes in
205citing papers in PubMed
13.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01787097 phase4completednot on this mapstarted 2013, after this paper: background citation

GR Activity in Induced Sputum Macrophages, and a Change in Inflammatory Biomarkers 2-hours After a Single Dose of Either Symbicort®/Budesonide/Formoterol or in Chronic Obstructive Pulmonary Disease (COPD)

TypeinterventionalSponsorImperial College LondonRan2013 to 2015Enrolled31ConditionsChronic Obstructive Lung DiseaseArmsSymbicort® total dose 400ug/12ug, Symbicort® total dose 800ug/24ug, Formoterol 24ug, BUD total dose 800ug
3 · Its place in the literature

Who cites it

205 citing papers in PubMed, 722 citations in OpenAlex.

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  11. Critical Windows: Exploring the Association Between Perinatal Trauma, Epigenetics, and Chronic Pain.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024
    Review
  12. Review
  13. Epigenetic Mechanisms Modulated by Glucocorticoids With a Focus on Cushing Syndrome.The Journal of clinical endocrinology and metabolism · 2024
    Review
  14. Review
  15. Review
  16. Acute Effects of Systemic Glucocorticoids on the Vocal Folds in a Pre-Clinical Model.The Annals of otology, rhinology, and laryngology · 2024
    Article
  17. Review
  18. Article
  19. Article
  20. Review

145 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

K ItoThoracic Medicine, Imperial College School of Medicine at the National Heart & Lung Institute, London, United Kingdom.
P J Barnes
I M Adcock
Imperial College London · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

We have investigated the ability of dexamethasone to regulate interleukin-1beta (IL-1beta)-induced gene expression, histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity. Low concentrations of dexamethasone (10(-10) M) repress IL-1beta-stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) expression and fail to stimulate secretory leukocyte proteinase inhibitor expression. Dexamethasone (10(-7) M) and IL-1beta (1 ng/ml) both stimulated HAT activity but showed a different pattern of histone H4 acetylation. Dexamethasone targeted lysines K5 and K16, whereas IL-1beta targeted K8 and K12. Low concentrations of dexamethasone (10(-10) M), which do not transactivate, repressed IL-1beta-stimulated K8 and K12 acetylation. Using chromatin immunoprecipitation assays, we show that dexamethasone inhibits IL-1beta-enhanced acetylated K8-associated GM-CSF promoter enrichment in a concentration-dependent manner. Neither IL-1beta nor dexamethasone elicited any GM-CSF promoter association at acetylated K5 residues. Furthermore, we show that GR acts both as a direct inhibitor of CREB binding protein (CBP)-associated HAT activity and also by recruiting HDAC2 to the p65-CBP HAT complex. This action does not involve de novo synthesis of HDAC protein or altered expression of CBP or p300/CBP-associated factor. This mechanism for glucocorticoid repression is novel and establishes that inhibition of histone acetylation is an additional level of control of inflammatory gene expression. This further suggests that pharmacological manipulation of of specific histone acetylation status is a potentially useful approach for the treatment of inflammatory diseases.

Indexed as

Repressor ProteinsAcetylationAcetyltransferasesBinding SitesCell Cycle ProteinsChromatinCREB-Binding ProteinDexamethasoneGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorHistone AcetyltransferasesHistone Deacetylase 2Histone DeacetylasesHistonesHumansInterleukin-1AcetyltransferasesCell Cycle ProteinsChromatinCREB-Binding ProteinCREBBP protein, humanDexamethasoneGranulocyte-Macrophage Colony-Stimulating FactorHistone AcetyltransferasesHistone Deacetylase 2Histone DeacetylasesHistonesInterleukin-1LysineNF-kappa BNuclear Proteinsp300-CBP-Associated Factorp300-CBP Transcription FactorsReceptors, GlucocorticoidRepressor ProteinsTrans-ActivatorsTranscription Factor RelATranscription Factors

Identifiers

PMID10958685
PMCPMC88765
OpenAlexW2166084959

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.