Evidence map›Paper›PMID 21510893›Full record

ArticleJournal of neuroinflammation2011

Specific PKC isoforms regulate LPS-stimulated iNOS induction in murine microglial cells.

Jie Wen, Rachel Ribeiro, Yumin Zhang

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 57 citations in OpenAlex.

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  6. Angiotensin Type 2 Receptor Pharmacological Agonist Relieves Neurocognitive Deficits via Reducing Neuroinflammation and Microglial Engulfment of Dendritic Spines.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
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  14. Involvement of c-Abl Kinase in Microglial Activation of NLRP3 Inflammasome and Impairment in Autolysosomal System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017
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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 1 institution in 1 country.

Jie WenDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Rachel Ribeiro
Yumin Zhang
Uniformed Services University of the Health Sciences · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExcessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) in reactive microglia is a major contributor to initiation/exacerbation of inflammatory and degenerative neurological diseases. Previous studies have indicated that activation of protein kinase C (PKC) can lead to iNOS induction. Because of the existence of various PKC isoforms and the ambiguous specificity of PKC inhibitors, it is unclear whether all PKC isoforms or a specific subset are involved in the expression of iNOS by reactive microglia. In this study, we employed molecular approaches to characterize the role of each specific PKC isoform in the regulation of iNOS expression in murine microglia.

methodsInduction of iNOS in response to bacterial endotoxin lipopolysaccharide (LPS) was measured in BV-2 murine microglia treated with class-specific PKC inhibitors, or transfected with siRNA to silence specific PKC isoforms. iNOS expression and MAPK phosphorylation were evaluated by western blot. The role of NF-κB in activated microglia was examined by determining NF-κB transcriptional response element- (TRE-) driven, promoter-mediated luciferase activity.

resultsMurine microglia expressed high levels of nPKCs, and expressed relatively low levels of cPKCs and aPKCs. All PKC inhibitors attenuated induction of iNOS in LPS-activated microglia. Knockdown of PKC δ and PKC β attenuated ERK1/2 and p38 phosphorylation, respectively, and blocked NF-κB activation that leads to the expression of iNOS in reactive microglia.

conclusionsOur results identify PKC δ and β as the major PKC isoforms regulating iNOS expression in reactive microglia. The signaling pathways mediated by PKC involve phosphorylation of distinct MAPKs and activation of NF-κB. These results may help in the design of novel and selective PKC inhibitors for the treatment of many inflammatory and neurological diseases in which production of NO plays a pathogenic role.

Indexed as

AnimalsCell LineEnzyme ActivationEnzyme InductionIsoenzymesLipopolysaccharidesMAP Kinase Signaling SystemMiceMicrogliaMitogen-Activated Protein KinasesNF-kappa BNitric OxideNitric Oxide Synthase Type IINitritesProtein Kinase CRNA, Small InterferingIsoenzymesLipopolysaccharidesMitogen-Activated Protein KinasesNF-kappa BNitric OxideNitric Oxide Synthase Type IINitritesProtein Kinase CRNA, Small Interfering

Identifiers

PMID21510893
PMCPMC3110130
OpenAlexW2169994469

What OpenQuestion holds

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LicenceCC BY
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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.