Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation.
Cell Differentiation
Extracellular Fluid
/ enzymology
Extracellular Space
/ metabolism
Humans
Inflammation
/ enzymology
Macrophage Colony-Stimulating Factor
/ metabolism
Macrophages
/ metabolism
Monocytes
/ cytology
Myeloid Cells
/ metabolism
Nicotinamide Phosphoribosyltransferase
/ chemistry
Pentosyltransferases
/ blood
Protein Binding
Risk Factors
Sepsis
/ blood
Toll-Like Receptor 4
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 09 2019
11 09 2019
Historique:
received:
26
03
2018
accepted:
14
08
2019
entrez:
13
9
2019
pubmed:
13
9
2019
medline:
24
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31511522
doi: 10.1038/s41467-019-12055-2
pii: 10.1038/s41467-019-12055-2
pmc: PMC6739309
doi:
Substances chimiques
Toll-Like Receptor 4
0
Macrophage Colony-Stimulating Factor
81627-83-0
Pentosyltransferases
EC 2.4.2.-
Nicotinamide Phosphoribosyltransferase
EC 2.4.2.12
nicotinate phosphoribosyltransferase
EC 6.3.4.21
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4116Références
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