Evidence map›Paper›PMID 28820283›Full record

ArticleAutophagy2017

N-3 PUFAs induce inflammatory tolerance by formation of KEAP1-containing SQSTM1/p62-bodies and activation of NFE2L2.

Jennifer Mildenberger, Ida Johansson, Ismail Sergin, Eli Kjøbli, Jan Kristian Damås, Babak Razani, Trude Helen Flo, Geir Bjørkøy

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 8% 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

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.

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  17. Conservative and Atypical Ferritins of Sponges.International journal of molecular sciences · 2021
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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

8 authors at 2 institutions in 2 countries.

Jennifer Mildenbergera Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences , Norwegian University of Science and Technology , Trondheim , Norway.
Ida Johanssona Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences , Norwegian University of Science and Technology , Trondheim , Norway.
Ismail Sergind Department of Medicine, Cardiovascular Division , Washington University School of Medicine , St. Louis , MO , USA.
Eli Kjøblib Department of Biomedical Laboratory Science, Faculty of Natural Sciences , Norwegian University of Science and Technology , Trondheim , Norway.
Jan Kristian Damåsa Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences , Norwegian University of Science and Technology , Trondheim , Norway.
Babak Razanid Department of Medicine, Cardiovascular Division , Washington University School of Medicine , St. Louis , MO , USA.
Trude Helen Floa Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences , Norwegian University of Science and Technology , Trondheim , Norway.
Geir Bjørkøya Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Faculty of Medicine and Health Sciences , Norwegian University of Science and Technology , Trondheim , Norway.
Norwegian University of Science and Technology · NOWashington University in St. Louis · US

Funding

THE ROLE OF MACROPHAGE LYSOSOMAL BIOGENESIS IN ATHEROSCLEROSISR01HL125838 · NHLBI · WASHINGTON UNIVERSITY · PI RAZANI, BABAK · 2015 to 2025
$4.6M
NHLBI NIH HHS R01 HL125838
6 · The paper itself

Abstract

Inflammation is crucial in the defense against infections but must be tightly controlled to limit detrimental hyperactivation. Our diet influences inflammatory processes and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have known anti-inflammatory effects. The balance of pro- and anti-inflammatory processes is coordinated by macrophages and macroautophagy/autophagy has recently emerged as a cellular process that dampens inflammation. Here we report that the n-3 PUFA docosahexaenoic acid (DHA) transiently induces cytosolic speckles of the autophagic receptor SQSTM1/p62 (sequestosome 1) (described as SQSTM1/p62-bodies) in macrophages. We suggest that the formation of SQSTM1/p62-bodies represents a fast mechanism of NFE2L2/Nrf2 (nuclear factor, erythroid 2 like 2) activation by recruitment of KEAP1 (kelch like ECH associated protein 1). Further, the autophagy receptor TAX1BP1 (Tax1 binding protein 1) and ubiquitin-editing enzyme TNFAIP3/A20 (TNF α induced protein 3) could be identified in DHA-induced SQSTM1/p62-bodies. Simultaneously, DHA strongly dampened the induction of pro-inflammatory genes including CXCL10 (C-X-C motif chemokine ligand 10) and we suggest that formation of SQSTM1/p62-bodies and activation of NFE2L2 leads to tolerance towards selective inflammatory stimuli. Finally, reduced CXCL10 levels were related to the improved clinical outcome in n-3 PUFA-supplemented heart-transplant patients and we propose CXCL10 as a robust marker for the clinical benefits mobilized by n-3 PUFA supplementation.

Indexed as

AnimalsAutophagyCells, CulturedFatty Acids, Omega-3Inclusion BodiesInflammationInflammation MediatorsKelch-Like ECH-Associated Protein 1MacrophagesMiceMice, KnockoutNF-E2-Related Factor 2Sequestosome-1 ProteinTranscriptional ActivationFatty Acids, Omega-3Inflammation MediatorsKeap1 protein, mouseKelch-Like ECH-Associated Protein 1Nfe2l2 protein, mouseNF-E2-Related Factor 2Sequestosome-1 ProteinSqstm1 protein, mouseaggregatesALISCXCL10DHAIKBKBIP10IRF1IRF3KEAP1LPSMDMNFE2L2NFKBOAomega-3p62PUFASQSTM1STAT1TLR4TNF

Identifiers

PMID28820283
PMCPMC5640206
OpenAlexW2745374599

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.