Proton pump inhibitors decrease eotaxin-3 expression in the proximal esophagus of children with esophageal eosinophilia

Jason Y. Park, Xi Zhang, Nathalie Nguyen, Rhonda F. Souza, Stuart J. Spechler, Edaire Cheng

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Objective: Besides reducing gastric acid secretion, proton pump inhibitors (PPIs) suppress Th2-cytokine-stimulated expression of an eosinophil chemoattractant (eotaxin-3) by esophageal epithelial cells through acid-independent, anti-inflammatory mechanisms. To explore acid-inhibitory and acid-independent, anti-inflammatory PPI effects in reducing esophageal eosinophilia, we studied eotaxin-3 expression by the proximal and distal esophagus of children with esophageal eosinophilia before and after PPI therapy. In vitro, we studied acid and bile salt effects on IL-13-stimulated eotaxin-3 expression by esophageal epithelial cells. Design: Among 264 children with esophageal eosinophilia seen at a tertiary pediatric hospital from 2008 through 2012, we identified 10 with esophageal biopsies before and after PPI treatment alone. We correlated epithelial cell eotaxin-3 immunostaining with eosinophil numbers in those biopsies. In vitro, we measured eotaxin-3 protein secretion by esophageal squamous cells stimulated with IL-13 and exposed to acid and/or bile salt media, with or without omeprazole. Results: There was strong correlation between peak eosinophil numbers and peak eotaxin-3-positive epithelial cell numbers in esophageal biopsies. Eotaxin-3 expression decreased significantly with PPIs only in the proximal esophagus. In esophageal cells, exposure to acid-bile salt medium significantly suppressed IL-13-induced eotaxin-3 secretion; omeprazole added to the acid-bile salt medium further suppressed that eotaxin-3 secretion, but not as profoundly as at pH-neutral conditions. Conclusion: In children with esophageal eosinophilia, PPIs significantly decrease eotaxin-3 expression in the proximal but not the distal esophagus. In esophageal squamous cells, acid and bile salts decrease Th2 cytokine-stimulated eotaxin-3 secretion profoundly, possibly explaining the disparate PPI effects on the proximal and distal esophagus. In the distal esophagus, where acid reflux is greatest, a PPI-induced reduction in acid reflux (an effect that could increase eotaxin-3 secretion induced by Th2 cytokines) might mask the acid-independent, anti-inflammatory PPI effect of decreasing cytokine-stimulated eotaxin-3 secretion.

Original languageEnglish (US)
Article numbere101391
JournalPloS one
Issue number7
StatePublished - Jul 2 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General


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