Evidence map›Paper›PMID 20959327›Full record

ArticleAnnals of the rheumatic diseases2010

NFκB activation and stimulation of chemokine production in normal human macrophages by the gadolinium-based magnetic resonance contrast agent Omniscan: possible role in the pathogenesis of nephrogenic systemic fibrosis.

Francesco Del Galdo, Peter J Wermuth, Sankar Addya, Paolo Fortina, Sergio A Jimenez

Open access · greenAbstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 41 citations in OpenAlex.

  1. Trial
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  10. Centrality of bone marrow in the severity of gadolinium-based contrast-induced systemic fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016
    Article
  11. Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2016
    Review
  12. Article
  13. Article
  14. Article
  15. Article
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  18. Minimizing risk of nephrogenic systemic fibrosis in cardiovascular magnetic resonance.Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2012
    Review
  19. Article
  20. Understanding nephrogenic systemic fibrosis.International journal of nephrology · 2012
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Francesco Del GaldoJefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Peter J Wermuth
Sankar Addya
Paolo Fortina
Sergio A Jimenez
Thomas Jefferson University · USJefferson Institute · US

Funding

BIOCHEMICAL AND VASCULAR ALTERATIONS IN SCLERODERMAR01AR019616 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI JIMENEZ, SERGIO A · 1986 to 2010
$3.2M
TRAINING IN MOLECULAR RHEUMATOLOGY &ORTHOPEDICST32AR007583 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI JIMENEZ, SERGIO A · 1994 to 2008
$1.3M
NIAMS NIH HHS R01 AR-019616NIAMS NIH HHS R01 AR019616NIAMS NIH HHS T32 AR-007583NIAMS NIH HHS T32 AR007583
6 · The paper itself

Abstract

objectiveNephrogenic systemic fibrosis (NSF) is a generalised fibrotic disorder occurring in certain individuals with renal insufficiency exposed to gadolinium-based contrast agents (GdBCA) for MRI. Histopathological examination of affected tissues shows increased numbers of activated macrophages. To elucidate the mechanisms responsible for macrophage activation, the effects of the GdBCA Omniscan on normal human macrophage global gene expression, chemokine production and nuclear factor κB (NFκB) activation was examined.

methodsNormal human monocyte-derived macrophages were incubated with Omniscan (50 mM) and their gene expression analysed by microarrays and real-time PCR. Macrophage chemokine production was assayed by multiplex ELISA. NFκB activation was assessed by NFκB nuclear localisation and quantitation of intracellular levels of inducible nitric oxide synthase (iNOS) protein. A specific cell-permeable NFκB peptide inhibitor was used to abrogate NFκB stimulation of chemokine and iNOS protein levels. CCL8/MCP-2 in affected skin of patients with NSF was examined by indirect immunofluorescence.

resultsOmniscan caused a profound change in the transcriptome of differentiated human normal macrophages in vitro, including a large increase in the expression of genes encoding CC and CXC chemokines. It induced rapid nuclear localisation of NFκB and stimulation of iNOS protein levels and chemokine production which were blocked by an NFκB inhibitory peptide. CCL8/MCP-2, the most upregulated chemokine following in vitro macrophage exposure to Omniscan, was strongly increased in NSF-affected skin.

conclusionThe GdBCA Omniscan induces potent stimulation of macrophage gene expression, NFκB activation and increased NFκB-mediated production of CC and CXC chemokines and iNOS. These alterations may play a crucial role in the pathogenesis of NSF.

Indexed as

Cell DifferentiationCell NucleusCells, CulturedChemokine CCL8ChemokinesContrast MediaGadolinium DTPAGene Expression RegulationHumansMacrophagesNephrogenic Fibrosing DermopathyNF-kappa BNitric Oxide Synthase Type IIPolymerase Chain ReactionSignal TransductionSkinCCL8 protein, humanChemokine CCL8ChemokinesContrast MediagadodiamideGadolinium DTPANF-kappa BNitric Oxide Synthase Type II

Identifiers

PMID20959327
PMCPMC6658210
OpenAlexW2132655120

What OpenQuestion holds

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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.