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PLoS One. 2014 Jul 2;9(7):e101391. doi: 10.1371/journal.pone.0101391. eCollection 2014.

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

Author information

1
Esophageal Diseases Center, Department of Pathology, Children's Medical Center, Eugene McDermott Center for Human Growth and Development, and the University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
2
Department of Pediatrics, Children's Medical Center, and the University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
3
Esophageal Diseases Center, Department of Internal Medicine, VA North Texas Health Care System, Harold C. Simmons Comprehensive Cancer Center, and the University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
4
Esophageal Diseases Center, Department of Internal Medicine, VA North Texas Health Care System, and the University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Department of Pediatrics, Children's Medical Center, and the University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.

Abstract

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.

PMID:
24988451
PMCID:
PMC4079672
DOI:
10.1371/journal.pone.0101391
[Indexed for MEDLINE]
Free PMC Article

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