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

Johanna Tiroch, Andreas Dunkel, Sonja Sterneder, Sofie Zehentner, Maik Behrens, Antonella Di Pizio, Jakob P. Ley, Barbara Lieder, Veronika Somoza (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

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 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.

Original languageEnglish
Pages (from-to)5314-5325
Number of pages12
JournalJournal of Agricultural and Food Chemistry
Volume71
Issue number13
DOIs
Publication statusPublished - 5 Apr 2023

Austrian Fields of Science 2012

  • 301110 Physiology
  • 104009 Food chemistry
  • 106023 Molecular biology

Keywords

  • bitter taste modulators
  • bitter taste receptors
  • bitter taste threshold
  • human gingival cells (HGF-1)
  • interleukin-6

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