Evidence map›Paper›PMID 18566416›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2008

Dynamic protein associations define two phases of IL-1beta transcriptional activation.

Yue Zhang, Simona Saccani, Hyunjin Shin, Barbara S Nikolajczyk

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
0.8field-weighted citation impact, top 24% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
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  6. Review
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  14. Transcriptional Regulation of Inflammasomes.International journal of molecular sciences · 2020
    Review
  15. Article
  16. Extracellular DNA, Neutrophil Extracellular Traps, and Inflammasome Activation in Severe Asthma.American journal of respiratory and critical care medicine · 2019
    Article
  17. Article
  18. Article
  19. Article
  20. Article
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

4 authors at 2 institutions in 2 countries.

Yue ZhangDepartment of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
Simona Saccani
Hyunjin Shin
Barbara S Nikolajczyk
Boston University · USMax Planck Society · DE

Funding

Mechanisms regulating immunoglobulin gene transcriptionR01AI054611 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI NIKOLAJCZYK, BARBARA · 2003 to 2007
$1.2M
NIAID NIH HHS R01 AI054611NIAID NIH HHS R01 AI54611
6 · The paper itself

Abstract

IL-1beta is a key proinflammatory cytokine with roles in multiple diseases. Monocytes package the IL-1beta promoter into a "poised architecture" characterized by a histone-free transcription start site and constitutive transcription factor associations. Upon LPS stimulation, multiple proteins inducibly associate with the IL-1beta gene. To understand how the complex combination of constitutive and inducible transcription factors activate the IL-1beta gene from a poised structure, we measured temporal changes in NF-kappaB and IFN regulatory factor (IRF) association with IL-1beta regulatory elements. Association of the p65 subunit of NF-kappaB peaks 30-60 min post-monocyte stimulation, and it shortly precedes IRF-4 recruitment to the IL-1beta enhancer and maximal mRNA production. In contrast, IRF-8/enhancer association decreases poststimulation. To test the importance of delayed IRF-4/enhancer association, we introduced a mutated PU.1 protein shown to prevent PU.1-mediated IRF-4 recruitment to the enhancer sequence. Mutated PU.1 initially increased IL-1beta mRNA followed by decreased mRNA levels 2-3 h poststimulation. Taken together, these data support a dynamic model of IL-1beta transcriptional activation in which a combination of IRF-8 and p65 drives the initial phase of IL-1beta transcription, while PU.1-mediated IRF-4 recruitment to the enhancer is important for the second phase. We further demonstrate that activation of both NF-kappaB and IRF-4 depends on CK2 kinase activity. Because IRF-4/enhancer association requires CK2 but not p65 activation, we conclude that CK2 triggers the IRF-4 and p65 pathways independently to serve as a master regulator of IL-1beta transcription.

Indexed as

Transcriptional ActivationAnimalsCasein Kinase IICell LineHumansInterferon Regulatory Factor-4Interferon Regulatory FactorsInterleukin-1betaMiceNF-kappa BPromoter Regions, GeneticProtein BindingProtein Kinase InhibitorsTranscription FactorsCasein Kinase IIInterferon Regulatory Factor-4Interferon Regulatory FactorsInterleukin-1betaNF-kappa BProtein Kinase InhibitorsTranscription Factors

Identifiers

PMID18566416
PMCPMC2967210
OpenAlexW1663773175

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.