Evidence map›Paper›PMID 34831450›Full record

ArticleCells2021

IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation.

Areej Al-Roub, Ashraf Al Madhoun, Nadeem Akhter, Reeby Thomas, Lavina Miranda, Texy Jacob, Ebaa Al-Ozairi, Fahd Al-Mulla, Sardar Sindhu, Rasheed Ahmad

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Biomolecules · 2025
    Article
  18. Article
  19. Review
  20. [Benefits of ω-3 fatty acids in Duchenne muscular dystrophy].Revista medica del Instituto Mexicano del Seguro Social · 2025
    Review
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

10 authors at 1 institution in 1 country.

Areej Al-RoubImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Ashraf Al MadhounGenetics & Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait.ORCID 0000-0001-8593-3878
Nadeem AkhterImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Reeby ThomasImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Lavina MirandaGenetics & Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Texy JacobImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Ebaa Al-OzairiMedical Division, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Fahd Al-MullaGenetics & Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait.ORCID 0000-0001-5409-3829
Sardar SindhuImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait.ORCID 0000-0001-9936-1575
Rasheed AhmadImmunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait.ORCID 0000-0001-5746-0743
Dasman Diabetes Institute · KW

Funding

Kuwait Foundation for the Advancement of Sciences RA AH 2016-007
6 · The paper itself

Abstract

IL-6 was found to be overexpressed in the adipose tissue of obese individuals, which may cause insulin resistance. However, the regulation of IL-6 in adipocytes in obesity setting remains to be explored. Since IL-1β and TNFα are increased in obese adipose tissue and promote inflammation, we investigated whether cooperation between IL-1β and TNFα influences the production of IL-6. Our data show that IL-1β and TNFα cooperatively enhance IL-6 expression in 3T3L-1 adipocytes. Similar results were seen in human adipocytes isolated from subcutaneous and visceral fat. Although adipocytes isolated from lean and obese adipose tissues showed similar responses for production of IL-6 when incubated with IL-1β/TNFα, secretion of IL-6 was higher in adipocytes from obese tissue. TNFα treatment enhanced CREB binding at CRE locus, which was further enhanced with IL-1β, and was associated with elevated histone acetylation at CRE locus. On the other hand, IL-1β treatments mediated C/EBPβ binding to NF-IL-6 consensus, but not sufficiently to mediate significant histone acetylation. Interestingly, treatment with both stimulatory factors amplifies CREB binding and H3K14 acetylation. Furthermore, histone acetylation inhibition by anacardic acid or curcumin reduces IL-6 production. Notably, inhibition of histone deacetylase (HDAC) activity by trichostatin A (TSA) resulted in the further elevation of IL-6 expression in response to combined treatment of adipocytes with IL-1β and TNFα. In conclusion, our results show that there is an additive interaction between IL-1β and TNFα that depends on CREB binding and H3K14 acetylation, and leads to the elevation of IL-6 expression in adipocytes, providing interesting pathophysiological connection among IL-1β, TNFα, and IL-6 in settings such as obesity.

Indexed as

Gene Expression Regulation3T3-L1 CellsAcetylationAdipocytesAnimalsBase SequenceCyclic AMP Response Element-Binding ProteinHistonesHumansHydroxamic AcidsInterleukin-1betaInterleukin-6LysineMicePromoter Regions, GeneticProtein BindingCyclic AMP Response Element-Binding ProteinHistonesHydroxamic AcidsInterleukin-1betaInterleukin-6Lysinetrichostatin ATumor Necrosis Factor-alphaadipocytesH3K14 acetylationinterleukin-1β (IL-1β)interleukin-6 (IL-6)tumor necrosis factor-alpha (TNFα)

Identifiers

PMID34831450
PMCPMC8619559
OpenAlexW3214689016

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.