EoE Module 10 References-Rochman et al J Allergy Clin Immunol 2021 Broad transcriptional response of the human esophageal epithelium to proton pump inhibitors

Rochman et al J Allergy Clin Immunol 2021 Broad transcriptional response of the human esophageal epithelium to proton pump inhibitors

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This study investigates the broad transcriptional effects of proton pump inhibitors (PPIs), specifically omeprazole and esomeprazole, on the human esophageal epithelium, focusing on mechanisms relevant to eosinophilic esophagitis (EoE)—a condition characterized by allergic inflammation. Although PPIs are widely used for treating EoE, their detailed impact on esophageal epithelial responses remains unclear. The researchers hypothesized that PPIs might counteract IL-13 mediated activities central to EoE.<br /><br />The methods involved using RT-PCR and RNA sequencing to analyze the gene expression changes induced by PPIs and IL-13 in human esophageal cells. The results revealed that a common set of 479 core genes is activated by PPI treatment, with effects partially mediated through the aryl hydrocarbon receptor (AHR) signaling pathway. Approximately 20% of the IL-13-induced transcriptome was reversed by PPI treatment. Notably, certain upregulated genes were linked to metabolic processes, while downregulated genes related to cell division—a significant aspect considering the hyperproliferation of cells observed in EoE.<br /><br />The study found that PPIs not only impact IL-13-driven pathways but also have broader effects on metabolic pathways and epithelial cell proliferation and differentiation. Furthermore, PPI treatment resulted in the reversed expression of several genes associated with EoE, suggesting that the benefits of PPIs extend beyond mere anti-inflammatory effects to include restoration of epithelial function and inhibition of unwanted cellular proliferation.<br /><br />In conclusion, the beneficial effects of PPIs in EoE treatment are likely due to their ability to modulate AHR-dependent and independent pathways impacting metabolism and cell cycle, thus providing a multi-faceted approach against EoE pathogenesis. This underlines the potential for combining PPI therapy with other treatments targeting inflammatory pathways like IL-13 blockade for a more comprehensive strategy against EoE.

Keywords

proton pump inhibitors

omeprazole

esomeprazole

eosinophilic esophagitis

IL-13

aryl hydrocarbon receptor

gene expression

metabolic pathways

epithelial function

cell proliferation