Anti-inflammatory mediators ST2 and SIGIRR are induced by diphenyldifluoroketone EF24 in lipopolysaccharide-stimulated dendritic cells.
Animals
Anti-Inflammatory Agents
/ pharmacology
Benzylidene Compounds
/ pharmacology
Cell Line
Dendritic Cells
/ drug effects
Inflammation Mediators
/ antagonists & inhibitors
Interleukin-1 Receptor-Like 1 Protein
/ antagonists & inhibitors
Interleukin-33
/ metabolism
Lipopolysaccharides
/ pharmacology
Mice
Mice, Inbred C57BL
NF-kappa B
/ metabolism
Piperidones
/ pharmacology
Proteasome Endopeptidase Complex
/ metabolism
Receptors, Interleukin-1
/ antagonists & inhibitors
Sp1 Transcription Factor
/ metabolism
Up-Regulation
/ drug effects
Dendritic cells
EF24
IL-1R
Inflammation
Lipopolysaccharide
SIGIRR
ST2
Journal
Immunobiology
ISSN: 1878-3279
Titre abrégé: Immunobiology
Pays: Netherlands
ID NLM: 8002742
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
05
09
2019
accepted:
26
11
2019
pubmed:
10
12
2019
medline:
25
5
2021
entrez:
9
12
2019
Statut:
ppublish
Résumé
The objective of this study was to investigate the effect of EF24, an NF-κB-inhibitor, on the expression of negative regulators in IL-1R pathway, namely ST2 and SIGIRR. Murine JAWS II dendritic cells (DC) were challenged with lipopolysaccharide (LPS, 100 ng/ml) for 4 h, followed by treatment with 10 μM EF24 for 1 h. ST2 and SIGIRR expression was monitored by qRT-PCR and immunoblotting. ST2L and MyD88 interaction was studied by co-immunoprecipitation, and IL-33, a ST2L ligand, was assayed by ELISA. Activation of transcription factor SP1 was examined by confocal microscopy, immunoblotting, and EMSA. The effect of EF24 on accumulation of ubiquitinated proteins in DCs and proteolysis of fluorogenic peptides by purified proteasome was studied. We found that EF24 upregulated the expression of ST2 and SIGIRR and decreased the interaction of the membrane-bound ST2 (ST2L) with MyD88, and significantly reduced IL-33 levels in LPS-stimulated DCs. Simultaneously it increased the activation of transcription factor SP1and restored the basal level of ubiquitinated proteins in LPS-stimulated DCs. Moreover, EF24 inhibited trypsin- and chymotrypsin-like activity of proteasome by directly interacting with 26S proteasome. The results suggest that EF24 activates endogenous anti-inflammatory arm of IL-1R signaling, most likely by stabilizing SP1 against proteasomal degradation.
Identifiants
pubmed: 31812341
pii: S0171-2985(19)30301-8
doi: 10.1016/j.imbio.2019.11.021
pmc: PMC7198325
mid: NIHMS1546114
pii:
doi:
Substances chimiques
3,5-bis(2-fluorobenzylidene)piperidin-4-one
0
Anti-Inflammatory Agents
0
Benzylidene Compounds
0
Il1rl1 protein, mouse
0
Inflammation Mediators
0
Interleukin-1 Receptor-Like 1 Protein
0
Interleukin-33
0
Lipopolysaccharides
0
NF-kappa B
0
Piperidones
0
Receptors, Interleukin-1
0
SIGIRR protein, mouse
0
Sp1 Transcription Factor
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
151886Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL104286
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier GmbH. All rights reserved.
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