Resveratrol and ivacaftor are additive G551D CFTR-channel potentiators: therapeutic implications for cystic fibrosis sinus disease

International Forum of Allergy & Rhinology
Do-Yeon ChoBradford A Woodworth

Abstract

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective Cl- transport and cause chronic bacterial infections in the upper and lower airways of cystic fibrosis (CF) patients. Ivacaftor is a CFTR potentiator that improves Cl- transport in CF patients with at least 1 copy of the G551D mutation. Resveratrol is also a potent CFTR potentiator that increases determinants of mucociliary transport. The objective of this study is to determine whether resveratrol and ivacaftor improve Cl- secretion in G551D CFTR over either agent alone. Fisher rat thyroid cells (FRT) transfected with G551D CFTR and human sinonasal epithelial cells (HSNE) containing the CFTR G551D mutation were subjected to pharmacologic manipulation of transepithelial ion transport in Ussing chambers. Activity was further evaluated using whole-cell patch clamp methods in G551D FRT cells. In G551D FRT cells, resveratrol (100 μM) and ivacaftor (10 μM) significantly increased Cl- transport (change in short-circuit current, δISC = μA/cm2 ) compared with single-agent and dimethylsulfoxide vehicle controls (resveratrol + ivacaftor 4.97 ± 0.57 vs ivacaftor 0.74 ± 0.12 vs resveratrol 2.96 ± 0.52 vs control 0.74 ± 0.12; p < 0.001). Maxi...Continue Reading

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Citations

Dec 5, 2018·International Forum of Allergy & Rhinology·Timothy L Smith
Apr 9, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Binyu LuThomas J Kelley
May 16, 2019·International Forum of Allergy & Rhinology·Michelle Menon Miyake, Benjamin S Bleier
Dec 25, 2019·International Forum of Allergy & Rhinology·Dong-Jin LimDo-Yeon Cho
Aug 31, 2020·Laryngoscope Investigative Otolaryngology·Harrison M ThompsonBradford A Woodworth
Oct 27, 2020·Frontiers in Pharmacology·Simone PatergnaniAlessandro Rimessi
Apr 8, 2021·Expert Opinion on Drug Discovery·Miquéias Lopes-PachecoGuido Veit
Sep 17, 2021·Molecular and Cellular Biochemistry·Victor Emanuel Miranda SoaresDébora Tavares de Resende E Silva

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