The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells

Sergio Oddi, Lucia Scipioni, Antonio Totaro, Clotilde Angelucci, Beatrice Dufrusine, Annalaura Sabatucci, Daniel Tortolani, Isabella Coletta, Maria Alessandra Alisi, Lorenzo Polenzani, Michael Assfalg, Carlo Caltagirone, Enrico Dainese, Mauro Maccarrone

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Abstract

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.

Original languageEnglish
Article number15155
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

ASJC Scopus subject areas

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    Oddi, S., Scipioni, L., Totaro, A., Angelucci, C., Dufrusine, B., Sabatucci, A., Tortolani, D., Coletta, I., Alisi, M. A., Polenzani, L., Assfalg, M., Caltagirone, C., Dainese, E., & Maccarrone, M. (2019). The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells. Scientific Reports, 9(1), [15155]. https://doi.org/10.1038/s41598-019-51691-y