Chronic rhinosinusitis with nasal polyps is associated with impaired TMEM16A-mediated epithelial chloride secretion

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most common chronic disorders limited therapeutic options. However, pathogenesis CRSwNP remains poorly understood.ObjectiveWe sought to determine role abnormalities in epithelial ion transport primary cultures and patients CRSwNP.MethodsWe studied transcript levels Cl? channels cystic fibrosis transmembrane conductance regulator protein 16A (TMEM16A) human healthy controls. Furthermore, we determined expression proinflammatory cytokines that have been implicated regulation (IL-1?, INF-?, TNF-?, IL-13) effects key TH2 signaling molecule IL-13 control cultures. Finally, measured vivo potential difference compare controls.ResultsBioelectric studies demonstrated Ca2+-activated secretion was reduced versus Transcript channel TMEM16A were increased Stimulation further restored Nasal measurements controls.ConclusionsThis study demonstrates TMEM16A-mediated epithelia CRSwNP. Our data suggest may be serve as a novel target Chronic understood. We Bioelectric This