posted on 2021-01-19, 05:03authored byJohanna Tiroch, Sonja Sterneder, Antonella Di Pizio, Barbara Lieder, Kathrin Hoelz, Ann-Katrin Holik, Marc Pignitter, Maik Behrens, Mark Somoza, Jakob P. Ley, Veronika Somoza
Recent
data have shown anti-inflammatory effects for trans-resveratrol (RSV) and rosmarinic acid (RA) in various immune-competent
cell models through reduction of lipopolysaccharide (LPS)-induced
interleukin 6 (IL-6) release. Because both compounds have been reported
to taste bitter, we hypothesized an involvement of human bitter taste
sensing receptors (TAS2Rs) on IL-6 release in LPS-treated human gingival
fibroblasts (HGF-1). First, the bitter taste intensity of RSV and
RA was compared in a sensory trial with 10 untrained panelists, of
whom 90% rated a 50 ppm of RSV in water solution more bitter than
50 ppm of RA. A mean 19 ± 6% reduction of the RSV-induced bitter
taste intensity was achieved by co-administration of 50 ppm of the
bitter-masking, TAS2R43 antagonist homoeriodictyol (HED). Mechanistic
experiments in a stably CRISPR-Cas9-edited TAS2R43ko gastric cell model revealed involvement of TAS2R43 in the HED-evoked
effect on RSV-induced proton secretion, whereas the cellular response
to RSV did not depend upon TAS2R43. Next, the IL-6
modulatory effect of 100 μM RSV was studied in LPS-treated immune-competent
HGF-1 cells. After 6 h of treatment, RSV reduced the LPS-induced IL-6
gene expression and protein
release by −46.2 ± 12.7 and −73.9 ± 2.99%,
respectively. This RSV-evoked effect was abolished by co-administration
of HED. Because real-time quantitative polymerase chain reaction analyses
revealed a regulation of TAS2R50 in RSV with or without
HED-treated HGF-1 cells, an siRNA knockdown approach of TAS2R50 was applied to verify TAS2R50 involvement in the
RSV-induced reduction of the LPS-evoked IL-6 release in HGT-1 cells.