The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells.
Sergio OddiLucia ScipioniAntonio TotaroClotilde AngelucciBeatrice DufrusineAnnalaura SabatucciDaniel TortolaniIsabella ColettaMaria Alessandra AlisiLorenzo PolenzaniMichael AssfalgCarlo CaltagironeEnrico DaineseMauro MaccarronePublished in: Scientific reports (2019)
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.
Keyphrases
- binding protein
- fatty acid
- induced apoptosis
- endothelial cells
- anti inflammatory
- inflammatory response
- cell cycle arrest
- signaling pathway
- induced pluripotent stem cells
- endoplasmic reticulum stress
- dendritic cells
- pluripotent stem cells
- toll like receptor
- poor prognosis
- pi k akt
- oxidative stress
- metabolic syndrome
- epithelial mesenchymal transition
- insulin resistance
- tyrosine kinase
- protein kinase
- mass spectrometry
- heat shock
- human health
- reactive oxygen species
- single molecule