The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells.
Active Transport, Cell Nucleus
/ drug effects
Anti-Inflammatory Agents
/ chemistry
Cell Line
Cell Nucleus
/ drug effects
Chemokine CCL2
/ metabolism
Fatty Acid-Binding Proteins
/ chemistry
Humans
Immunologic Factors
/ pharmacology
Indazoles
/ chemistry
Interleukin-8
/ metabolism
Lipopolysaccharides
Models, Biological
Monocytes
/ drug effects
PPAR gamma
/ metabolism
Propionates
/ chemistry
Protein Binding
/ drug effects
Up-Regulation
/ drug effects
p38 Mitogen-Activated Protein Kinases
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 10 2019
22 10 2019
Historique:
received:
05
07
2019
accepted:
07
10
2019
entrez:
24
10
2019
pubmed:
24
10
2019
medline:
29
10
2020
Statut:
epublish
Résumé
We investigated the cellular and molecular mechanisms by which bindarit, a small indazolic derivative with prominent anti-inflammatory effects, exerts its immunoregulatory activity in lipopolysaccharide (LPS) stimulated human monocytic cells. We found that bindarit differentially regulates the release of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), enhancing the release of IL-8 and reducing that of MCP-1. These effects specifically required a functional interaction between bindarit and fatty acid binding protein 4 (FABP4), a lipid chaperone that couples intracellular lipid mediators to their biological targets and signaling pathways. We further demonstrated that bindarit can directly interact with FABP4 by increasing its expression and nuclear localization, thus impacting on peroxisome proliferator-activated receptor γ (PPARγ) and LPS-dependent kinase signaling. Taken together, these findings suggest a potential key-role of FABP4 in the immunomodulatory activity of bindarit, and extend the spectrum of its possible therapeutic applications to FABP4 modulation.
Identifiants
pubmed: 31641194
doi: 10.1038/s41598-019-51691-y
pii: 10.1038/s41598-019-51691-y
pmc: PMC6805920
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Chemokine CCL2
0
FABP4 protein, human
0
Fatty Acid-Binding Proteins
0
Immunologic Factors
0
Indazoles
0
Interleukin-8
0
Lipopolysaccharides
0
PPAR gamma
0
Propionates
0
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
bindarit
JQ11LH711M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15155Références
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