The anti-inflammatory effect of trans-resveratrol in HGF-1 cells is mediated by the human bitter taste sensing receptor TAS2R50*

Poster presentation

Johanna Tiroch ¹, Sonja Sterneder ¹, Antonella Di Pizio ², Barbara Lieder ¹, Kathrin Hoelz ³, Ann-Katrin Holik ¹, Marc Pignitter ¹, Maik Behrens ², Mark Somoza ^{2, 3, 4}, Jakob P. Ley ⁵, Veronika Somoza ^{1, 2, 6}

¹ Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., ² Leibniz Institute of Food Systems Biology at the Technical University of Munich, Freising, Germany., ³ Department of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Vienna, Austria., ⁴ Chair of Food Chemistry and Molecular Sensory Science, Technical University Munich, Freising, Germany., ⁵ Symrise AG, Holzminden, Germany., ⁶ Chair for Nutritional Systems Biology, Technical University Munich, Freising, Germany.

Trans-resveratrol (RSV) and rosmarinic acid (RA) have shown their anti-inflammatory effects in various immune competent cell models via inhibition of lipopolysaccharide (LPS)-induced TNF-α- and IL-6-release in recent data. Additionally, both substances are reported to taste bitter. Therefore, we wanted to deduce their involvement on human bitter taste sensing receptors (TAS2Rs) in the RSV- and RA-evoked anti-inflammatory effect in LPS-treated human gingival fibroblasts (HGF- 1) in culture. Initially, we compared the bitter taste intensity of RSV and RA in a sensory trial with 10 untrained panelists, 90 % rated a 50 ppm RSV in water solution more bitter than 50 ppm RA. The bitterness of RSV was able to be reduced by a mean of 19 % due to the co-administration of 50 ppm bitter masker homoeriodictyol (HED). The greater bitter taste intensity of RSV compared to RA was verified by means in the human gastric cell model (HGT-1 cells), which show a TAS2R-linked proton secretion. Afterwards, the immune-modulatory effect of 100 µM RSV was studied in 10 µg/mL LPS-treated immune competent HGF-1 cells. After 6 hrs of treatment, RSV reduced LPS-induced IL-6 gene expression and release by -46.19 ± 12.67 % and -73.81 ± 10.58 %, respectively. By co-administration of HED, this RSV-evoked effect was abolished. Since qRT-PCR analyses demonstrated a regulation of TAS2R50 in RSV w/o HED treated HGF-1 cells, an siRNA knock-down approach was applied to demonstrated involvement in the RSV-induced reduction of LPS-evoked IL-6 release in HGT-1 cells. Subsequently, a chemical interaction between RSV and LPS was excluded by LC-MS/MS analyses. Furthermore, the molecular mechanism of the interaction between RSV and the TAS2R50 were identified by a putative binding mode and performed by induced-fit docking simulations.