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Hops bitter \u03b2\u2010acids lupulone and colupulone possess potent antibacterial activities and, as T2R1, T2R14, and\/or T2R40 agonists, may improve the impaired mucociliary clearance described in CRS patients. We investigated these molecules as alternative treatments to antibiotics in CRS management based on their antibacterial and T2Rs agonists properties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human nasal primary cells (HNECs) and RPMI2650 cells cultures were used as study models. T2Rs expression in cell culture models and human nasal tissue was assessed using immunofluorescence, quantitative PCR, and Western blot. We performed calcium imaging and cilia beat frequency experiments to investigate T2Rs activation in study models in response to lupulone and colupulone stimulations. Finally, we studied hops \u03b2\u2010acids cytotoxicity on cells using CellEvent, crystal violet, lactate dehydrogenase assays, immunofluorescence, and transepithelial electrical resistance assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We confirmed lupulone and colupulone potent antibacterial effect on CRS\u2010relevant methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> but found minimal impact on <jats:italic>P. aeruginosa<\/jats:italic>. We also report T2R1, T2R14 and T2R40 expression in HNECs and RPMI2650 cell cultures. Lupulone and colupulone induced an increase in cytosolic calcium that appeared dependent on T2Rs signaling. This response was accompanied by mitochondrial membrane depolarization, cellular energy stress, decreased cell proliferation, ciliostasis, and HNECs remodeling after a single exposure to lupulone at micromolar concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that hops \u03b2\u2010acids may not be beneficial as treatments in CRS patients and instead contribute to the disease by impairing cell health and further deteriorating the MCC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.23487","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T12:08:35Z","timestamp":1731499715000},"page":"287-302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hops bitter \u03b2\u2010acids have antibacterial effects against sinonasal <i>Staphylococcus aureus<\/i> but also induce sinonasal cilia and mitochondrial dysfunction"],"prefix":"10.1002","volume":"15","author":[{"given":"Yobouet Ines","family":"Kouakou","sequence":"first","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel C.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Hui","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoey A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray Z.","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithin D.","family":"Adappa","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam A.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Rhinology Department of Otorhinolaryngology\u2010Head Neck Surgery Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Monell Chemical Senses Center  Philadelphia Pennsylvania USA"},{"name":"Corporal Michael J. 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