Anti-inflammatory activity of small-molecule antagonists of Toll-like receptor 2 (TLR2) in mice.
Animals
Anti-Inflammatory Agents
/ pharmacology
HEK293 Cells
HMGB1 Protein
/ metabolism
Humans
Lipopeptides
/ immunology
Macrophages
/ drug effects
Mice
Mice, Inbred C57BL
Nitric Oxide
/ metabolism
RAW 264.7 Cells
Sepsis
/ drug therapy
Toll-Like Receptor 2
/ antagonists & inhibitors
Tumor Necrosis Factor-alpha
/ immunology
Inflammatory cytokine
Sepsis
Small-molecule
TLR
Journal
Immunobiology
ISSN: 1878-3279
Titre abrégé: Immunobiology
Pays: Netherlands
ID NLM: 8002742
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
24
09
2018
revised:
07
11
2018
accepted:
12
11
2018
pubmed:
5
12
2018
medline:
18
12
2019
entrez:
5
12
2018
Statut:
ppublish
Résumé
Toll-like receptor 2 (TLR2) is currently investigated as a potential therapeutic target in diseases with underlying inflammation like sepsis and arthritis. We reported the discovery, by virtual screening and biological testing, of eight TLR2 antagonists (AT1-AT8) which showed TLR2-inhibitory activity in human cells (Murgueitio et al., 2014). In this study, we have deepened in the mechanism of action and selectivity (TLR2/1 or TLR2/6) of those compounds in mouse primary cells and in vivo. The antagonists reduced, in a dose-dependent way the TNFα production (e.g. AT5 IC
Identifiants
pubmed: 30509503
pii: S0171-2985(18)30137-2
doi: 10.1016/j.imbio.2018.11.004
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
HMGB1 Protein
0
Lipopeptides
0
Pam(3)CSK(4) peptide
0
TLR2 protein, human
0
Tlr2 protein, mouse
0
Toll-Like Receptor 2
0
Tumor Necrosis Factor-alpha
0
Nitric Oxide
31C4KY9ESH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-9Subventions
Organisme : Austrian Science Fund FWF
ID : P 30779
Pays : Austria
Informations de copyright
Copyright © 2018 Elsevier GmbH. All rights reserved.