Proton pump inhibitors modulate the barrier dysfunction caused by IL-13 in the epithelium in eosinophilic esophagitis. Proton pump inhibitors modulate the barrier dysfunction caused by IL-13 in the epithelium in eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder triggered by specific food antigens, characterized by eosinophil-rich multicellular inflammation and structural changes in the epithelium. Treatment options for EoE include dietary therapy, pharmacological therapy, or a combination of both, chosen based on the patient's preference and clinical progression. Pharmacological options include proton pump inhibitors (PPIs), corticosteroids, and biologic therapy. Although PPI therapy is used for EoE management, its underlying mechanism of action remains unclear. To investigate the effects of omeprazole, an orally bioavailable PPI commonly used for EoE therapy, on the dynamics of esophageal epithelial barrier function and inflammation, we employed air-liquid interface (ALI) culture. We examined how omeprazole affects gene expression changes caused by IL-13 treatment. ALI cultures were treated with 100 ng/ml of IL-13 and/or 50 µM of acid-activated omeprazole for 96 hours, and bulk RNA sequencing was performed to analyze the epithelial-specific transcriptomes of IL-13 and/or omeprazole-treated ALI. Our findings suggest potential gene interactions where omeprazole may mitigate transcriptional changes induced by IL-13, indicating that omeprazole may attenuate IL-13 mediated epithelial dysfunction relevant to EoE pathophysiology by modulating pathways associated with inflammation, tissue repair, and cell-cell communication. Overall design: Effect of Omeprazole on gene expression profiling of air-liquid interface (ALI) derived from telomerase-immortalized human esophageal keratinocyte cell line, EPC2-hTERT.

嗜酸性食管炎（Eosinophilic esophagitis, EoE）是一类由特定食物抗原诱发的慢性免疫介导性疾病，以富含嗜酸性粒细胞的多细胞炎症反应及上皮组织结构重塑为核心特征。EoE的治疗手段包括饮食干预、药物治疗或二者联合，需结合患者个体偏好与临床进程选择最优方案。临床常用的药物治疗方案涵盖质子泵抑制剂（proton pump inhibitors, PPIs）、糖皮质激素及生物制剂。尽管PPI疗法已被应用于EoE的临床管理，但其确切的作用机制仍未阐明。
为探究奥美拉唑——一种常用于EoE治疗的口服生物可利用PPI——对食管上皮屏障功能与炎症动态的调控效应，本研究采用气液界面（air-liquid interface, ALI）培养模型。我们系统分析了奥美拉唑对白细胞介素13（IL-13）诱导的基因表达变化的影响。将ALI培养物以100 ng/ml的IL-13和/或50 µM酸激活型奥美拉唑处理96小时后，通过批量RNA测序（bulk RNA sequencing）分析经上述处理的ALI的上皮特异性转录组特征。
本研究结果提示存在潜在的基因交互网络：奥美拉唑可显著缓解IL-13诱导的转录组改变，表明其或可通过调控炎症、组织修复及细胞间通讯相关通路，减轻IL-13介导的、与EoE病理生理机制密切相关的上皮功能障碍。
总体实验设计：探究奥美拉唑对端粒酶永生化人食管角质形成细胞系EPC2-hTERT来源的气液界面（ALI）培养物的基因表达谱的影响。