Evidence map›Paper›PMID 31511522›Full record

ArticleNature communications2019

Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation.

Antonella Managò, Valentina Audrito, Francesca Mazzola, Leonardo Sorci, Federica Gaudino, Katiuscia Gizzi, Nicoletta Vitale, Danny Incarnato, Gabriele Minazzato, Alice Ianniello and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 4% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

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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

17 authors at 8 institutions in 3 countries.

Antonella ManagòDepartment of Medical Sciences, University of Turin, Turin, Italy.
Valentina AudritoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Francesca MazzolaDepartment of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.
Leonardo SorciDepartment of Materials, Environmental Sciences and Urban Planning, Division of Bioinformatics and Biochemistry, Polytechnic University of Marche, Ancona, Italy.ORCID http://orcid.org/0000-0002-4356-8873
Federica GaudinoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Katiuscia GizziItalian Institute for Genomic Medicine, Turin, Italy.
Nicoletta VitaleDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Danny IncarnatoDepartment of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, The Netherlands.
Gabriele MinazzatoDepartment of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
Alice IannielloDepartment of Laboratory Medicine, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy.
Antonio VarrialeInstitute of Food Science, CNR, Avellino, Italy.
Sabato D'AuriaInstitute of Food Science, CNR, Avellino, Italy.
Giulio MengozziDepartment of Laboratory Medicine, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy.
Gianfranco PolitanoDepartment of Control and Computer Engineering, Polytechnic University of Turin, Turin, Italy.ORCID http://orcid.org/0000-0001-5268-9899
Salvatore OlivieroItalian Institute for Genomic Medicine, Turin, Italy.ORCID http://orcid.org/0000-0002-3405-765X
Nadia RaffaelliDepartment of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
Silvia DeaglioDepartment of Medical Sciences, University of Turin, Turin, Italy. silvia.deaglio@unito.it.ORCID http://orcid.org/0000-0003-0632-5036
Marche Polytechnic University · ITUniversity of Turin · ITAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITInstitute of Food Science · ITItalian institute for Genomic Medicine · ITDepartment of Medical Sciences · BYPolitecnico di Torino · ITUniversity of Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and mouse macrophages to NAPRT activates the inflammasome and NF-κB for secretion of inflammatory cytokines. Furthermore, NAPRT enhances monocyte differentiation into macrophages by inducing macrophage colony-stimulating factor. These NAPRT-induced effects are independent of NAD-biosynthetic activity, but rely on NAPRT binding to TLR4. In line with our finding that NAPRT mediates endotoxin tolerance in vitro and in vivo, sera from patients with sepsis contain the highest levels of NAPRT, compared to patients with other chronic inflammatory conditions. Together, these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation.

Indexed as

Cell DifferentiationExtracellular FluidExtracellular SpaceHumansInflammationMacrophage Colony-Stimulating FactorMacrophagesMonocytesMyeloid CellsNicotinamide PhosphoribosyltransferasePentosyltransferasesProtein BindingRisk FactorsSepsisToll-Like Receptor 4Macrophage Colony-Stimulating FactorNicotinamide Phosphoribosyltransferasenicotinate phosphoribosyltransferasePentosyltransferasesToll-Like Receptor 4

Identifiers

PMID31511522
PMCPMC6739309
OpenAlexW2973065709

What OpenQuestion holds

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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.