Evidence map›Paper›PMID 27554194›Full record

ArticleScientific reports2016

PAFR activation of NF-κB p65 or p105 precursor dictates pro- and anti-inflammatory responses during TLR activation in murine macrophages.

Edson K Ishizuka, Luciano Ribeiro Filgueiras, Francisco J Rios, Carlos H Serezani, Sonia Jancar

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 23% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Myeloid MyD88 restricts CD8Scientific reports · 2023
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
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

5 authors at 3 institutions in 3 countries.

Edson K IshizukaDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Luciano Ribeiro FilgueirasDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Francisco J RiosInstitute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Carlos H SerezaniDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, (46202) United States of America.
Sonia JancarDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Universidade de São Paulo · BRIndiana University – Purdue University Indianapolis · USUniversity of Glasgow · GB

Funding

Phosphatase and tensin homolog PTEN actions in polymicrobial sepsisR01HL124159 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SEREZANI, C. HENRIQUE · 2014 to 2022
$4.2M
Regulation of Toll-like receptor-induced NFkB activation by Gai-coupled receptorsR00HL103777 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI SEREZANI, C. HENRIQUE · 2012 to 2014
$713k
Regulation of Toll-like receptor-induced NFkB activation by Gai-coupled receptorsK99HL103777 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SEREZANI, C. HENRIQUE · 2010 to 2011
$242k
LTB4 and the control of methicilin resistant Staphylococcus aureus infectionR03AI110990 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI SEREZANI, C. HENRIQUE · 2015 to 2016
$156k
NHLBI NIH HHS K99 HL103777NHLBI NIH HHS R00 HL103777NHLBI NIH HHS R01 HL124159NIAID NIH HHS R03 AI110990
6 · The paper itself

Abstract

Platelet-activating factor receptor (PAFR) is a G protein-coupled receptor (GPCR) implicated in many diseases. Toll-like receptors (TLRs) play a critical role in shaping innate and adaptive immune responses. In this study, we investigated whether PAFR signaling changes the macrophages responsiveness to agonists of TLR2 (Pam3Cys), TLR4 (LPS), and TLR3 agonist Poly(I:C). Exogenous PAF inhibited the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) and increased anti-inflammatory IL-10 in macrophages challenged with Pam3Cys and LPS, but not with Poly (I:C). PAF did not affect mRNA expression of MyD88, suggesting that PAF acts downstream the adaptor. PAF inhibited LPS-induced phosphorylation of NF-κB p65 and increased NF-κB p105 phosphorylation, which is processed in the proteasome to generate p50 subunit. The PAF potentiation of IL-10 production was dependent on proteasome processing but independent of NF-κB transactivation domain. Inhibition of p50 abolished the PAF-induced IL-10 production. These findings indicate that the impaired transcriptional activity of the p65 subunit and the enhanced p105 phosphorylation induced by PAF are responsible for down regulation of pro-inflammatory cytokines and up regulation of IL-10, respectively, in LPS-challenged macrophages. Together, our data unveil a heretofore unrecognized role for PAFR in modulating activation of NF-κB in macrophages.

Indexed as

AnimalsCytokinesInflammationInflammation MediatorsInterleukin-10LipopolysaccharidesLipoproteinsMacrophages, PeritonealMaleMice, Inbred C57BLMyeloid Differentiation Factor 88NF-kappa B p50 SubunitPlatelet Activating FactorPlatelet Membrane GlycoproteinsReceptors, G-Protein-CoupledToll-Like Receptor 2CytokinesIL10 protein, mouseInflammation MediatorsInterleukin-10LipopolysaccharidesLipoproteinsMyd88 protein, mouseMyeloid Differentiation Factor 88NF-kappa B p50 SubunitNfkb1 protein, mouseN-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysinePlatelet Activating Factorplatelet activating factor receptorPlatelet Membrane GlycoproteinsReceptors, G-Protein-CoupledTlr2 protein, mouseTlr4 protein, mouseToll-Like Receptor 2Toll-Like Receptor 4Toll-Like ReceptorsTranscription Factor RelA

Identifiers

PMID27554194
PMCPMC4995467
OpenAlexW2515188239

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.