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 language | English |
|---|---|
| Article number | 15155 |
| Journal | Scientific Reports |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 1 2019 |
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The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells. / Oddi, Sergio; Scipioni, Lucia; Totaro, Antonio; Angelucci, Clotilde; Dufrusine, Beatrice; Sabatucci, Annalaura; Tortolani, Daniel; Coletta, Isabella; Alisi, Maria Alessandra; Polenzani, Lorenzo; Assfalg, Michael; Caltagirone, Carlo; Dainese, Enrico; Maccarrone, Mauro.
In: Scientific Reports, Vol. 9, No. 1, 15155, 01.12.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The anti-inflammatory agent bindarit acts as a modulator of fatty acid-binding protein 4 in human monocytic cells
AU - Oddi, Sergio
AU - Scipioni, Lucia
AU - Totaro, Antonio
AU - Angelucci, Clotilde
AU - Dufrusine, Beatrice
AU - Sabatucci, Annalaura
AU - Tortolani, Daniel
AU - Coletta, Isabella
AU - Alisi, Maria Alessandra
AU - Polenzani, Lorenzo
AU - Assfalg, Michael
AU - Caltagirone, Carlo
AU - Dainese, Enrico
AU - Maccarrone, Mauro
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85073744908&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073744908&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-51691-y
DO - 10.1038/s41598-019-51691-y
M3 - Article
C2 - 31641194
AN - SCOPUS:85073744908
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 15155
ER -