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Pepsin in nonacidic refluxate can damage hypopharyngeal epithelial cells. Ann Otol Rhinol Laryngol 2009 Sep;118(9):677-85



Pubmed ID




Scopus ID

2-s2.0-70349438977   79 Citations


OBJECTIVES: Studies using combined multichannel intraluminal impedance with pH monitoring reveal a role for nonacidic reflux in laryngopharyngeal symptoms and injury. We have discovered that pepsin is taken up by laryngeal epithelial cells by receptor-mediated endocytosis. This finding reveals a novel mechanism by which pepsin could cause cell damage, potentially even in nonacidic refluxate. The objective of this study was to determine whether pepsin, at pH 7.4 and thus in nonacidic refluxate, causes cell damage.

METHODS: Cultured hypopharyngeal epithelial (FaDu) cells were exposed to human pepsin (0.1 mg/mL) at pH 7.4 for either 1 hour or 12 hours at 37 degrees C and analyzed by electron microscopy, cytotoxicity assay, and SuperArray.

RESULTS: We report mitochondrial and Golgi complex damage in cells exposed to pepsin at neutral pH, observed by electron microscopy. We also report cell toxicity of pepsin at pH 7.4, measured by a cytotoxicity assay. Furthermore, using SuperArray, we found that pepsin at pH 7.4 significantly alters the expression levels of multiple genes implicated in stress and toxicity.

CONCLUSIONS: These findings are perhaps the first to explain why many patients have symptoms and injury associated with nonacidic reflux, and could have important implications for the development of new therapies for reflux, such as pepsin receptor antagonists and/or irreversible inhibitors of peptic activity.

Author List

Johnston N, Wells CW, Samuels TL, Blumin JH


Joel H. Blumin MD Chief, Professor in the Otolaryngology department at Medical College of Wisconsin
Nikki Johnston PhD Associate Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cells, Cultured
Epithelial Cells
Esophageal pH Monitoring
Gastroesophageal Reflux
Hydrogen-Ion Concentration
Microscopy, Electron
Pepsin A
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280