Amprenavir inhibits pepsin‐mediated laryngeal epithelial disruption and E‐cadherin cleavage in vitro

Background Laryngopharyngeal reflux (LPR) causes chronic cough, throat clearing, hoarseness, and dysphagia can promote laryngeal carcinogenesis. More than 20% of the US population suffers from LPR there is no effective medical therapy. Pepsin a predominant source damage during which disrupts barrier function potentially via E-cadherin cleavage proteolysis downstream matrix metalloproteinase (MMP) dysregulation. Fosamprenavir (FDA-approved HIV therapeutic prodrug amprenavir) pepsin-inhibiting candidate shown to rescue in an mouse model. This study aimed examine amprenavir protection against monolayer disruption related MMP dysregulation vitro. Methods Laryngeal (TVC HPV) cells were exposed buffered saline, pH 7.4 or 4 ± 1 mg/mL pepsin (10–60 min). Analysis was performed by microscopy, Western blot, real time polymerase chain reaction (qPCR). Results Amprenavir (1 μM) rescued acid-mediated cell dissociation (p < .05). acid caused indicative regulated intramembrane (RIP) increased MMP-1,3,7,9,14 24-h postexposure Acid alone did not cause cleavage. (10 protected MMP-1,9,14 induction Conclusions Amprenavir, at serum concentrations achievable provided manufacturer's recommended dose fosamprenavir for HIV, protects pepsin-mediated dissociation, cleavage, thought contribute dysfunction symptoms LPR. conversion epithelia, saliva, relative drug efficacies model are under investigation inform development inhaled formulations