NOTCH3 signaling is essential for NF-κB activation in TLR-activated macrophages.
Animals
Gene Expression Regulation
Humans
Inflammation
/ immunology
Macrophage Activation
Macrophages
/ cytology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes
/ immunology
NF-kappa B
/ immunology
RAW 264.7 Cells
Receptor, Notch3
/ physiology
Signal Transduction
Toll-Like Receptors
/ immunology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 09 2020
09 09 2020
Historique:
received:
05
12
2019
accepted:
19
08
2020
entrez:
10
9
2020
pubmed:
11
9
2020
medline:
16
3
2021
Statut:
epublish
Résumé
Macrophage activation by Toll receptors is an essential event in the development of the response against pathogens. NOTCH signaling pathway is involved in the control of macrophage activation and the inflammatory processes. In this work, we have characterized NOTCH signaling in macrophages activated by Toll-like receptor (TLR) triggering and determined that DLL1 and DLL4 are the main ligands responsible for NOTCH signaling. We have identified ADAM10 as the main protease implicated in NOTCH processing and activation. We have also observed that furin, which processes NOTCH receptors, is induced by TLR signaling in a NOTCH-dependent manner. NOTCH3 is the only NOTCH receptor expressed in resting macrophages. Its expression increased rapidly in the first hours after TLR4 activation, followed by a gradual decrease, which was coincident with an elevation of the expression of the other NOTCH receptors. All NOTCH1, 2 and 3 contribute to the increased NOTCH signaling detected in activated macrophages. We also observed a crosstalk between NOTCH3 and NOTCH1 during macrophage activation. Finally, our results highlight the relevance of NOTCH3 in the activation of NF-κB, increasing p65 phosphorylation by p38 MAP kinase. Our data identify, for the first time, NOTCH3 as a relevant player in the control of inflammation.
Identifiants
pubmed: 32908186
doi: 10.1038/s41598-020-71810-4
pii: 10.1038/s41598-020-71810-4
pmc: PMC7481794
doi:
Substances chimiques
NF-kappa B
0
Notch3 protein, mouse
0
Receptor, Notch3
0
Toll-Like Receptors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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