Evidence map›Paper›PMID 23028621›Full record

ArticlePloS one2012

MicroRNA-146a: a key regulator of astrocyte-mediated inflammatory response.

Anand Iyer, Emanuele Zurolo, Avanita Prabowo, Kees Fluiter, Wim G M Spliet, Peter C van Rijen, Jan A Gorter, Eleonora Aronica

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 4 pooled it
9.9field-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.

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

189 citing papers in PubMed, 4 syntheses or guidelines pooled it, 321 citations in OpenAlex.

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129 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 4 institutions in 1 country.

Anand IyerDepartment of Neuro-Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Emanuele Zurolo
Avanita Prabowo
Kees Fluiter
Wim G M Spliet
Peter C van Rijen
Jan A Gorter
Eleonora Aronica
Academic Medical Center · NLUniversity Medical Center Utrecht · NLStichting Epilepsie Instellingen Nederland · NLUniversity of Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increasing evidence supports the involvement of microRNAs (miRNA) in the regulation of inflammation in human neurological disorders. In the present study we investigated the role of miR-146a, a key regulator of the innate immune response, in the modulation of astrocyte-mediated inflammation. Using Taqman PCR and in situ hybridization, we studied the expression of miR-146a in epilepsy-associated glioneuronal lesions which are characterized by prominent activation of the innate immune response. In addition, cultured human astrocytes were used to study the regulation of miR-146a expression in response to proinflammatory cytokines. qPCR and western blot were used to evaluate the effects of overexpression or knockdown of miR-146a on IL-1β signaling. Downstream signaling in the IL-1β pathway, as well as the expression of IL-6 and COX-2 were evaluated by western blot and ELISA. Release several cytokines was evaluated using a human magnetic multiplex cytokine assay on a Luminex® 100™/200™ platform. Increased expression of miR-146a was observed in glioneuronal lesions by Taqman PCR. MiR-146a expression in human glial cell cultures was strongly induced by IL-1β and blocked by IL-1β receptor antagonist. Modulation of miR-146a expression by transfection of astrocytes with anti-miR146a or mimic, regulated the mRNA expression levels of downstream targets of miR-146a (IRAK-1, IRAK-2 and TRAF-6) and the expression of IRAK-1 protein. In addition, the expression of IL-6 and COX-2 upon IL-1β stimulation was suppressed by increased levels of miR-146a and increased by the reduction of miR-146a. Modulation of miR-146a expression affected also the release of several cytokines such as IL-6 and TNF-α. Our observations indicate that in response to inflammatory cues, miR-146a was induced as a negative-feedback regulator of the astrocyte-mediated inflammatory response. This supports an important role of miR-146a in human neurological disorders associated with chronic inflammation and suggests that this miR may represent a novel target for therapeutic strategies.

Indexed as

AstrocytesBrain DiseasesCell Line, TumorCyclooxygenase 2EpilepsyFemaleGangliogliomaGene Expression RegulationHumansImmunity, InnateInflammation MediatorsInterleukin-1betaInterleukin-1 Receptor-Associated KinasesInterleukin-6MaleMalformations of Cortical DevelopmentCyclooxygenase 2Inflammation MediatorsInterleukin-1betaInterleukin-1 Receptor-Associated KinasesInterleukin-6MicroRNAsMIRN146 microRNA, humanNF-kappa BReceptors, Interleukin-1TNF Receptor-Associated Factor 6Toll-Like Receptors

Identifiers

PMID23028621
PMCPMC3441440
OpenAlexW2138125988

What OpenQuestion holds

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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 OpenQuestion graph.