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The Impact of Pepsin on Human Nasal Epithelial Cells In Vitro: A Potential Mechanism for Extraesophageal Reflux Induced Chronic Rhinosinusitis. Ann Otol Rhinol Laryngol 2015 Dec;124(12):957-64



Pubmed ID




Scopus ID

2-s2.0-84953378153   13 Citations


OBJECTIVES: To describe potential mechanisms by which pepsin induces inflammation in refractive chronic rhinosinusitis (CRS). Our hypothesis was that pepsin induces mitochondrial damage and cytokine expression in human nasal epithelial cells (HNEpC) in vitro.

METHODS: Western blot was used to detect pepsin in sinus lavages from patients with CRS and controls. The HNEpC cells were treated with pepsin (pH 7; 0.1 mg/mL) for 1 or 16 hours and routine electron microscopy (EM) and MTT assay were performed. Cytokine ELISA was performed on media collected from HNEpC cells 16 hours following a 1-hour pepsin treatment.

RESULTS: Pepsin was detected in sinus lavages from 4 out of 6 CRS patients and 0 out of 3 controls. The EM showed mitochondrial damage in pepsin-treated HNEpC cells but not in control cells. The MTT assay demonstrated reduced mitochondrial activity in pepsin-treated HNEpC cells compared to controls (P < .001). Pepsin increased IL-1A (P = .003) and IL-6 (P = .04) expression in HNEpC cells.

CONCLUSIONS: Pepsin in sinus lavages from patients with CRS is consistent with previous studies. This study reveals the damaging effect of pepsin on mitochondria in nasal epithelial cells in vitro. Cytokines previously associated with CRS were elevated following pepsin treatment of HNEpC cells in vitro. These results demonstrate mechanisms by which pepsin may potentiate CRS.

Author List

Southwood JE, Hoekzema CR, Samuels TL, Wells C, Poetker DM, Johnston N, Loehrl TA


Nikki Johnston PhD Associate Professor in the Otolaryngology department at Medical College of Wisconsin
David M. Poetker MD Chief, Professor in the Otolaryngology department at Medical College of Wisconsin
Jessica E. Southwood MD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin

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

Case-Control Studies
Cells, Cultured
Chronic Disease
Epithelial Cells
Gastrointestinal Agents
Microscopy, Electron, Transmission
Middle Aged
Nasal Lavage Fluid
Nasal Mucosa
Pepsin A
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00