Evidence map›Paper›PMID 9421488›Full record

ArticleThe Journal of clinical investigation1998

Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene.

D D'Ambrosio, M Cippitelli, M G Cocciolo, D Mazzeo, P Di Lucia, R Lang, F Sinigaglia, P Panina-Bordignon

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01656070 (Vitamin D Status and T Cell Phenotype in HIV-infected Youth Supplemented With Cholecalciferol), which is not on this map. Cited by 218 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
218citing papers in PubMed, 6 pooled it
15.8field-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.

NCT01656070 phase2completednot on this mapstarted 2011, after this paper: background citation

Vitamin D Status and T Cell Phenotype in HIV-infected Youth Supplemented With Cholecalciferol: a Randomized Clinical Trial.

TypeinterventionalSponsorUniversity of MilanRan2011 to 2012Enrolled50ConditionsHIV Disease, Vitamin D Deficiency, Hypovitaminosis D, HyperparathyroidismArmsoral cholecalciferol 1000000 UI (vitamin D3), Placebo
3 · Its place in the literature

Who cites it

218 citing papers in PubMed, 6 syntheses or guidelines pooled it, 653 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Observational
  17. Article
  18. The Role of Vitamin D and Vitamin D Receptor in Sepsis.Current issues in molecular biology · 2025
    Review
  19. Vitamin D efficacy in type 1 and type 2 diabetes.Journal of bone and mineral metabolism · 2024
    Review
  20. Review

158 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

8 authors at 3 institutions in 2 countries.

D D'AmbrosioRoche Milano Ricerche, I-20132, Milan, Italy. dambrod@dibit.hsr.it
M Cippitelli
M G Cocciolo
D Mazzeo
P Di Lucia
R Lang
F Sinigaglia
P Panina-Bordignon
Roche (Switzerland) · CHIRCCS Ospedale San Raffaele · ITSapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interleukin 12 (IL-12), produced by myelomonocytic cells, plays a pivotal role in the development of T helper 1 (Th1) cells, which are involved in the pathogenesis of chronic inflammatory autoimmune disorders. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] inhibits IL-12 production by activated macrophages and dendritic cells, thus providing a novel interpretation to its immunosuppressive properties. 1,25(OH)2D3 significantly inhibits mRNA expression for both IL-12 p35 and p40 subunits acting at the transcriptional level. The effect of 1,25(OH)2D3 on p40 promoter activation was analyzed by cotransfecting monocytic RAW264.7 cells with p40 promoter/reporter constructs and expression vectors for vitamin D3 receptor (VDR) and/or retinoid X receptor (RXRalpha). We observed transcriptional repression of the p40 gene by 1,25(OH)2D3, which required coexpression of VDR with RXR and an intact VDR DNA-binding domain. The repressive effect maps to a region in the p40 promoter containing a binding site for NF-kappaB (p40-kappaB). Deletion of the p40-kappaB site abrogates part of the inhibitory effect on the p40 promoter, confirming the functional relevance of this site. Activation of monocytic THP-1 cells in the presence of 1,25(OH)2D3 results in reduced binding to the p40-kappaB site. Thus, 1,25(OH)2D3 may negatively regulate IL-12 production by downregulation of NF-kappaB activation and binding to the p40-kappaB sequence.

Indexed as

AnimalsBinding SitesCalcitriolCell LineDown-RegulationGene Expression RegulationHumansInterleukin-12MiceMonocytesNF-kappa BNF-kappa B p50 SubunitPromoter Regions, GeneticReceptors, CalcitriolReceptors, Retinoic AcidRetinoid X ReceptorsCalcitriolInterleukin-12NF-kappa BNF-kappa B p50 SubunitReceptors, CalcitriolReceptors, Retinoic AcidRetinoid X ReceptorsRNA, MessengerTranscription Factor RelATranscription Factors

Identifiers

PMID9421488
PMCPMC508562
OpenAlexW2083373216

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.