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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/572eb2b99d5749e3b72bf31cc3872ede
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spelling	oai:doaj.org-article:572eb2b99d5749e3b72bf31cc3872ede2021-12-02T15:10:04ZThe anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells10.1038/s41598-019-51691-y2045-2322https://doaj.org/article/572eb2b99d5749e3b72bf31cc3872ede2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51691-yhttps://doaj.org/toc/2045-2322Abstract 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.Sergio OddiLucia ScipioniAntonio TotaroClotilde AngelucciBeatrice DufrusineAnnalaura SabatucciDaniel TortolaniIsabella ColettaMaria Alessandra AlisiLorenzo PolenzaniMichael AssfalgCarlo CaltagironeEnrico DaineseMauro MaccarroneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
description	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.
format	article
author	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
author_facet	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
author_sort	Sergio Oddi
title	The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
title_short	The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
title_full	The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
title_fullStr	The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
title_full_unstemmed	The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
title_sort	anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/572eb2b99d5749e3b72bf31cc3872ede
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The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells

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