Human Gingival Fibroblasts as a Novel Cell Model Describing the Association between Bitter Taste Thresholds and Interleukin-6 Release

Abstract

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 <i>Porphyromonas gingivalis</i> (<i>Pg-</i>LPS). Recently, we demonstrated <i>trans</i>-resveratrol to repress the <i>Pg</i>-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 <i>Pg</i>-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 <i>Pg</i>-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 <i>R</i>² = 0.60 (<i>p</i> < 0.01), exceeding respective data for the test compounds from a well-established native cell model, the HGT-1 cells, with <i>R</i>² = 0.153 (<i>p</i> = 0.263). In conclusion, we provide a predictive model for bitter tasting compounds with a potential to act as anti-inflammatory substances.