TY - JOUR
T1 - Human Gingival Fibroblasts as a Novel Cell Model Describing the Association between Bitter Taste Thresholds and Interleukin-6 Release
AU - Tiroch, Johanna
AU - Dunkel, Andreas
AU - Sterneder, Sonja
AU - Zehentner, Sofie
AU - Behrens, Maik
AU - Di Pizio, Antonella
AU - Ley, Jakob P.
AU - Lieder, Barbara
AU - Somoza, Veronika
N1 - Accession Number: WOS:000951732600001
PubMed ID: 36943188
PY - 2023/4/5
Y1 - 2023/4/5
N2 - Human gingival fibroblast cells (HGF-1 cells) present an important cell model to investigate the gingiva’s response to inflammatory stimuli such as lipopolysaccharides from Porphyromonas gingivalis (Pg-LPS). Recently, we demonstrated trans-resveratrol to repress the Pg-LPS evoked release of the pro-inflammatory cytokine interleukin-6 (IL-6) via involvement of bitter taste sensing receptor TAS2R50 in HGF-1 cells. Since HGF-1 cells express most of the known 25 TAS2Rs, we hypothesized an association between a compound’s bitter taste threshold and its repressing effect on the Pg-LPS evoked IL-6 release by HGF-1 cells. To verify our hypothesis, 11 compounds were selected from the chemical bitter space and subjected to the HGF-1 cell assay, spanning a concentration range between 0.1 μM and 50 mM. In the first set of experiments, the specific role of TAS2R50 was excluded by results from structurally diverse TAS2R agonists and antagonists and by means of a molecular docking approach. In the second set of experiments, the HGF-1 cell response was used to establish a linear association between a compound’s effective concentration to repress the Pg-LPS evoked IL-6 release by 25% and its bitter taste threshold concentration published in the literature. The Pearson correlation coefficient revealed for this linear association was R2 = 0.60 (p < 0.01), exceeding respective data for the test compounds from a well-established native cell model, the HGT-1 cells, with R2 = 0.153 (p = 0.263). In conclusion, we provide a predictive model for bitter tasting compounds with a potential to act as anti-inflammatory substances.
AB - Human gingival fibroblast cells (HGF-1 cells) present an important cell model to investigate the gingiva’s response to inflammatory stimuli such as lipopolysaccharides from Porphyromonas gingivalis (Pg-LPS). Recently, we demonstrated trans-resveratrol to repress the Pg-LPS evoked release of the pro-inflammatory cytokine interleukin-6 (IL-6) via involvement of bitter taste sensing receptor TAS2R50 in HGF-1 cells. Since HGF-1 cells express most of the known 25 TAS2Rs, we hypothesized an association between a compound’s bitter taste threshold and its repressing effect on the Pg-LPS evoked IL-6 release by HGF-1 cells. To verify our hypothesis, 11 compounds were selected from the chemical bitter space and subjected to the HGF-1 cell assay, spanning a concentration range between 0.1 μM and 50 mM. In the first set of experiments, the specific role of TAS2R50 was excluded by results from structurally diverse TAS2R agonists and antagonists and by means of a molecular docking approach. In the second set of experiments, the HGF-1 cell response was used to establish a linear association between a compound’s effective concentration to repress the Pg-LPS evoked IL-6 release by 25% and its bitter taste threshold concentration published in the literature. The Pearson correlation coefficient revealed for this linear association was R2 = 0.60 (p < 0.01), exceeding respective data for the test compounds from a well-established native cell model, the HGT-1 cells, with R2 = 0.153 (p = 0.263). In conclusion, we provide a predictive model for bitter tasting compounds with a potential to act as anti-inflammatory substances.
KW - bitter taste modulators
KW - bitter taste receptors
KW - bitter taste threshold
KW - human gingival cells (HGF-1)
KW - interleukin-6
UR - http://www.scopus.com/inward/record.url?scp=85151238604&partnerID=8YFLogxK
U2 - 10.1021/acs.jafc.2c06979
DO - 10.1021/acs.jafc.2c06979
M3 - Article
C2 - 36943188
AN - SCOPUS:85151238604
SN - 0021-8561
VL - 71
SP - 5314
EP - 5325
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
IS - 13
ER -