Inès and Joel have a great paper available online (open access, so freely available) today at International Forum of Allergy and Rhinology! They studied bitter beta-acids from hops (yes, the same hops used for beer). We hypothesized that these compounds (lupulone and colupulone) might be beneficial by both activating bitter taste receptors (taste family 2 receptors, or T2Rs) in the nose to stimulate beneficial innate defense responses. These compounds, often referred to as "antibiotics" in older medical literature, also have antibacterial properties. Lupulone and colupulone were used for tuberculosis in people after World War II, but they were abandoned in favor of conventional antibiotics as antibiotics improved for TB, and because the beta-acids had some gastrointestinal side effects. Inès and Joel carried out a very rigorous and interesting study using a variety of techniques, including fluorescent biosensors, live cell imaging of indicator dyes, biochemistry, microbiology, etc. in both primary nasal cells and nasal cancer cells.
They found that while lupulone and colupulone are bactericidal against methicillin-resistant Staph. aureus (MRSA), these compounds also have detrimental impacts on nasal epithelial mitochondria and cilia function. This is possibly because they activate a new T2R isoform, T2R1, which does not have strict cilia localization like many of the other T2R isoforms we studied in nasal epithelial cells. Lupulone and Colupulone also stimulated robust remodeling in primary cells differentiated at air-liquid interface. Epithelial remodeling is the process by which the cells that make up the epithelium change in type and/or composition. Remodeling occurs in a variety of airway diseases like chronic rhinosinusitis or cystic fibrosis. While lupulone and colupulone specifically don't look promising for development as new topical T2R-targeting or antibacterial therapies, this work sheds new light onto how T2Rs signal in the nose, including new mechanisms of how they might impinge on epithelial remodeling. This study demonstrates that we don't yet know everything about what T2Rs do in the nose. Derivatives of these compounds might also be useful if analogues can be made to not activate T2R1 but still have anti-MRSA properties.
