IL-6 release by a human gingival fibroblast cell line correlates with the bitter taste threshold of the stimulant
Thu-P1-004
Presented by: Sonja Sterneder
Fibroblasts are the predominant cell type in gingival connective tissues and play an essential role during acute inflammation, releasing cytokines that recruit immune cells to counter environmental stimuli. Activation of bitter sensing chemoreceptors (TAS2Rs) has been demonstrated to repress the release of lipopolysaccharide (LPS)-induced pro-inflammatory cytokines by the human gingival fibroblast cell line HGF-1. Since these results indicate that TAS2Rs activation in HGF-1 cells mediates the release of pro-inflammatory cytokines, we hypothesized that the release of the pro-inflammatory interleukin 6 (IL-6) by HGF-1 cells is correlated with sensory bitter taste thresholds.
In previous work, we showed that trans-resveratrol repressed the LPS-induced IL-6 release in HGF-1 cells via TAS2R50 involvement. We, therefore, performed molecular docking on TAS2R50 and functional cell-based experiments using a number of TAS2R agonists selected from the chemical bitter space in combination with TAS2R antagonists to demonstrate that this cellular response to taste-relevant concentrations is not TAS2R50 specific. In a next set of experiments, the number of test compounds selected from the chemical bitter space was expanded to cover the structural diversity of bitter compounds with reported psychophysical threshold. Functional experiments revealed a correlation between the reported bitter taste threshold of tastants and their modulating effect on the LPS-induced IL-6 release by HGF-1 cells. These results were validated against our previously established parietal cell assay using the HGT-1 cell line, and found to have an improved correlation with bitter taste thresholds (HGF-1: R²=0.60, p<0.01 vs. HGT-1: R²=0.15, p=0.26).
In conclusion, the HGF-1 cell assay presents a suitable model for the identification of bitter compounds and modulators. In addition, our results strongly support the anti-inflammatory potential of bitter compounds which has to be substantiated by clinical studies.
In previous work, we showed that trans-resveratrol repressed the LPS-induced IL-6 release in HGF-1 cells via TAS2R50 involvement. We, therefore, performed molecular docking on TAS2R50 and functional cell-based experiments using a number of TAS2R agonists selected from the chemical bitter space in combination with TAS2R antagonists to demonstrate that this cellular response to taste-relevant concentrations is not TAS2R50 specific. In a next set of experiments, the number of test compounds selected from the chemical bitter space was expanded to cover the structural diversity of bitter compounds with reported psychophysical threshold. Functional experiments revealed a correlation between the reported bitter taste threshold of tastants and their modulating effect on the LPS-induced IL-6 release by HGF-1 cells. These results were validated against our previously established parietal cell assay using the HGT-1 cell line, and found to have an improved correlation with bitter taste thresholds (HGF-1: R²=0.60, p<0.01 vs. HGT-1: R²=0.15, p=0.26).
In conclusion, the HGF-1 cell assay presents a suitable model for the identification of bitter compounds and modulators. In addition, our results strongly support the anti-inflammatory potential of bitter compounds which has to be substantiated by clinical studies.