Evidence map›Paper›PMID 30471562›Full record

ArticleThe Journal of nutritional biochemistry2019

Vitamin E δ-tocotrienol inhibits TNF-α-stimulated NF-κB activation by up-regulation of anti-inflammatory A20 via modulation of sphingolipid including elevation of intracellular dihydroceramides.

Chao Yang, Qing Jiang

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

Article in The Journal of nutritional biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 3 pooled it
1.2field-weighted citation impact, top 24% 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, 3 syntheses or guidelines pooled it, 41 citations in OpenAlex.

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  16. Revisiting the therapeutic potential of tocotrienol.BioFactors (Oxford, England) · 2022
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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

2 authors at 1 institution in 1 country.

Chao YangDepartment of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA.
Qing JiangDepartment of Nutrition Science, Purdue University, West Lafayette, IN 47907, USA. Electronic address: qjiang@purdue.edu.
Purdue University West Lafayette · US

Funding

Phase II studies of gamma tocopherol as an intervention for environmental asthmaR01ES023349 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEDEN, DAVID B. · 2013 to 2017
$3.7M
NIEHS NIH HHS R01 ES023349
6 · The paper itself

Abstract

Nuclear factor-κB (NF-κB) regulates inflammation and cell survival, and is considered a potential target for anti-inflammatory and anti-cancer therapy. δ-Tocotrienol (δTE), a vitamin E form, has been shown to inhibit NF-κB, but the mechanism underlying this action is not clear. In the present study, we show that δTE inhibited TNF-α-induced activation of NF-κB and LPS-stimulated IL-6 in a dose- and time-dependent manner in Raw 264.7 macrophages. δTE potently inhibited TNF-α-induced phosphorylation of transforming growth factor β-activated kinase 1 (TAK1), an upstream kinase essential for the activation of NF-κB. Interestingly, δTE significantly increased the expression of A20 and to a less extent, cylindromatosis (CYLD), both of which are inhibitors of NF-κB. The importance of induction of A20 in δTE's anti-NF-κB effect is validated in A20 knockout cells where δTE's inhibition of NF-κB was largely diminished. In pursuit of the cause for A20 induction, we found that δTE treatment caused rapid and persistent elevation of dihydroceramides, while decreased ceramides initially but increased ceramides during prolonged treatment. These changes of sphingolipids were accompanied by increased cellular stress markers. Importantly, δTE's induction of A20 and inhibition of NF-κB activation were partially counteracted by myriocin, a potent inhibitor of de novo synthesis of sphingolipids, indicating a critical role of sphingolipid modulation in δTE-mediated effects. Since dihydroceramide has been shown to induce A20 and inhibit NF-κB in RAW cells, we conclude that that δTE inhibits NF-κB activation by enhancing its negative regulator A20 as a result of modulating sphingolipids especially elevation of dihydroceramides.

Indexed as

AnimalsAnti-Inflammatory AgentsCeramidesDeubiquitinating Enzyme CYLDFibroblastsInterleukin-6LipopolysaccharidesMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceMice, KnockoutNF-kappa BRAW 264.7 CellsSphingolipidsTumor Necrosis Factor alpha-Induced Protein 3Vitamin EAnti-Inflammatory AgentsCeramidesCYLD protein, mouseDeubiquitinating Enzyme CYLDInterleukin-6interleukin-6, mouseLipopolysaccharidesMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesNF-kappa BSphingolipidsTnfaip3 protein, mousetocotrienol, deltaTumor Necrosis Factor alpha-Induced Protein 3Vitamin EA20Cellular stressInflammationNF-κBSphingolipidsTocotrienolVitamin E

Identifiers

PMID30471562
PMCPMC6363855
OpenAlexW2899411341

What OpenQuestion holds

Textmetadata
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.