Objective Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) can have similar clinical and histological features. Proton pump inhibitors (PPIs) are used to distinguish the disorders, with the assumption that only GORD can respond to PPIs. Oesophageal expression of eotaxin-3 stimulated by Th2 cytokines might contribute to oesophageal eosinophilia in EoE. Th2 cytokine effects on the oesophagus in GORD are not known. The objective of the authors was to explore the molecular mechanisms of Th2 cytokines on eotaxin-3 expression by oesophageal squamous cells from patients with GORD and EoE, and the effects of omeprazole on that eotaxin-3 expression.
Design Using telomerase-immortalised and primary cultures of oesophageal squamous cells from GORD and EoE patients, the authors measured eotaxin-3 protein secretion stimulated by Th2 cytokines (interleukin (IL)-4 and IL-13). Eotaxin-3 promoter constructs were used to study transcriptional regulation. Cytokine-induced eotaxin-3 mRNA and protein expression were measured in the presence or absence of omeprazole.
Results There were no significant differences between EoE and GORD primary cells in cytokine-stimulated eotaxin-3 protein secretion levels. In EoE and GORD cell lines, IL-4 and IL-13 activated the eotaxin-3 promoter, and significantly increased eotaxin-3 mRNA and protein expression. Omeprazole blocked the cytokine-stimulated increase in eotaxin-3 mRNA and protein expression in EoE and GORD cell lines.
Conclusion Oesophageal squamous cells from GORD and EoE patients express similar levels of eotaxin-3 when stimulated by Th2 cytokines, and omeprazole blocks that eotaxin-3 expression. These findings suggest that PPIs might have eosinophil-reducing effects independent of effects on acid reflux and that response to PPIs might not distinguish EoE from GORD.
- Eosinophilic oesophagitis
- proton pump inhibitors
- Th2 cytokines
- epithelial cells
- epithelial barrier
- Barrett's metaplasia
- gastro-oesphageal junction
- molecular carcinogenesis
- Barrett's carcinoma
- Barrett's oesophagus
- molecular biology
- acid-related diseases
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Funding This work was supported by the Office of Medical Research, Departments of Veterans Affairs (RFS, SJS, DHW), the National Institutes of Health (R01-DK63621 to RFS, R01-CA134571 to RFS and SJS, T32 DK007745-14 to EC, K12 HD-068369-01 to EC) and the American Gastroenterological Association Institute (Fellow to Faculty Transition Award to EC).
Competing interests None.
Ethics approval Ethics approval was provided by the institutional review board on human studies at the Dallas VA Medical Center.
Provenance and peer review Not commissioned; externally peer reviewed.