Pepsin as a causal agent of inflammation during nonacidic reflux.
OBJECTIVE
To investigate the contribution of pepsin to inflammation attributed to nonacidic gastric reflux via analysis of inflammatory cytokine and cytokine receptor gene expression in pepsin-treated human hypopharyngeal epithelial cells in vitro.


METHODS
Translational research.


METHODS
This study was performed in an academic research laboratory.


METHODS
Human hypopharyngeal epithelial cells were incubated with or without pepsin (0.1 mg/mL) at pH 7.4, 37 degrees C, overnight. Expression of 84 inflammatory cytokines and cytokine receptors was analyzed via RT(2) qPCR array.


RESULTS
Expression of a number of inflammatory cytokines and receptors was altered in human hypopharyngeal epithelial cells following overnight treatment with pepsin at neutral pH. Greater than 1.5-fold change in gene expression was detected for CCL20, CCL26, IL8, IL1F10, IL1A, IL5, BCL6, CCR6, and CXCL14 (P < 0.05).


CONCLUSIONS
Exposure of hypopharyngeal cells to pepsin in a nonacidic environment induces the expression of several pro-inflammatory cytokines and receptors, including those known to be involved in inflammation of esophageal epithelium in response to reflux and which contribute to the pathophysiology of reflux esophagitis. These data indicate that refluxed pepsin may contribute to laryngeal inflammation associated with nonacidic gastric reflux, including that experienced by patients despite maximal acid suppression therapy.
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Tina L
TL
Samuels
Nikki
N
Johnston
D016207:Cytokines / Q000032:analysis / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects; D004942:Esophagitis, Peptic / Q000209:etiology*; D006801:Humans; D007013:Hypopharynx / Q000187:drug effects / Q000473:pathology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology*; D010434:Pepsin A / Q000502:physiology*; D018121:Receptors, Cytokine / Q000032:analysis / Q000235:genetics
D016207:Cytokines; D018121:Receptors, Cytokine; D010434:Pepsin A