Evidence map›Paper›PMID 19921217›Full record

ArticleInternational journal of colorectal disease2010

Influence of NFkappaB inhibitors on IL-1beta-induced chemokine CXCL8 and -10 expression levels in intestinal epithelial cell lines: glucocorticoid ineffectiveness and paradoxical effect of PDTC.

Yeruva Sunil, Giuliano Ramadori, Dirk Raddatzc

Open access · hybridAbstract read
In one paragraph

Article in International journal of colorectal disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

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  15. NF-κΒ inhibition is ineffective in blocking cytokine-induced IL-8 production but P38 and STAT1 inhibitors are effective.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2012
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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 2 institutions in 1 country.

Yeruva SunilCentre for Internal Medicine, Department of Gastroenterology and Endocrinology, University of Goettingen, Goettingen, Germany.
Giuliano Ramadori
Dirk Raddatzc
University of Göttingen · DEMedizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeActivation of intestinal epithelial cell (IEC) nuclear factor kappaB (NFkappaB) and the consequent chemokine upregulation are crucial events in inflammatory bowel disease (IBD) pathogenesis. Not much is known about the consequences of NFkappaB inhibition in terms of chemokine expression in intestinal cells. Therefore, we aimed to evaluate the efficacy of compounds known to disrupt the NFkappaB pathway on NFkappaB transcriptional activity and CXCL8 and CXCL10 gene expression in intestinal cell lines.

methodsThe influence of NFkappaB inhibitors (dexamethasone, pyrrolidine dithiocarbamate (PDTC) and BAY 11-7082) on IL-1beta-induced NFkappaB transcriptional activity was investigated by transient transfection of Caco-2 cells with an NFkappaB-secreted alkaline phosphatase reporter plasmid. Il-1beta stimulated CXCL8 and CXCL10 mRNA and protein expression and was studied in Caco-2 and HT29 cells in the presence and absence of the NFkappaB inhibitors by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent serologic assay, respectively. To reveal alternative signalling cascades, experiments were also performed in the presence of the p38MAPK inhibitor SB 203580 and the ERK inhibitor PD 98059.

resultsDexamethasone did not downregulate chemokine expression sufficiently, probably due to a lack of glucocorticoid receptors in these cells. While BAY11-7082 inhibited chemokine expression, PDTC led to a paradoxical upregulation of CXCL8 in Caco-2 cells, which could be prevented by inhibition of p38MAPK.

conclusionThese data explain the frequent unresponsiveness of IBD to glucocorticoid treatment and suggest that alternative NFkappaB inhibition in IECs might be of use in IBD therapy. Drug development based on measuring anti-NFkappaB activity might be misleading and should therefore also include studies on relevant gene products.

Indexed as

Caco-2 CellsChemokine CXCL10DexamethasoneEpithelial CellsFlavonoidsGene Expression Regulation, NeoplasticGenes, ReporterGlucocorticoidsHT29 CellsHumansImidazolesInterleukin-1betaInterleukin-8IntestinesNF-kappa BNitriles2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one3-(4-methylphenylsulfonyl)-2-propenenitrileChemokine CXCL10CXCL10 protein, humanCXCL8 protein, humanDexamethasoneFlavonoidsGlucocorticoidsImidazolesInterleukin-1betaInterleukin-8NF-kappa BNitrilesPyridinespyrrolidine dithiocarbamic acidPyrrolidinesReceptors, GlucocorticoidRNA, MessengerSB 203580SulfonesThiocarbamates

Identifiers

PMID19921217
PMCPMC2814033
OpenAlexW2096795899

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.