Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD.
Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD.
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DOI：
10.1136/gutjnl-2012-302250
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发表时间：
2013-06
期刊：
影响因子：
24.5
通讯作者：
Souza RF
中科院分区：
文献类型：
--
作者：
Cheng E;Zhang X;Huo X;Yu C;Zhang Q;Wang DH;Spechler SJ;Souza RF
嗜酸性食管炎（EoE）和胃食管反流病（GORD）可能具有相似的临床和组织学特征。质子泵抑制剂（PPI）用于区分疾病，假设只有GORD可以响应PPI。食管Eotaxin-3的表达由Th 2细胞因子刺激可能有助于EoE中食管嗜酸性粒细胞增多。Th 2细胞因子对GORD食管的影响尚不清楚。本研究的目的是探讨Th 2细胞因子对GORD和EoE患者食管鳞状细胞表达eotaxin-3的分子机制，以及奥美拉唑对Eotaxin-3表达的影响。使用来自GORD和EOE患者的食管鳞状细胞的端粒酶永生化和原代培养物，我们测量了Th 2细胞因子（IL-4和IL-13）刺激的嗜酸性粒细胞趋化因子-3蛋白分泌。Eotaxin-3启动子构建体用于研究转录调控。在存在或不存在奥美拉唑的情况下测量细胞因子诱导的嗜酸性粒细胞趋化因子-3 mRNA和蛋白表达。在EoE和GORD原代细胞中，马槟榔碱刺激的eotaxin-3蛋白分泌水平没有显著差异。在EoE和GORD细胞系中，IL-4和IL-13激活eotaxin-3启动子，并显著增加eotaxin-3 mRNA和蛋白表达。在EoE和GORD细胞系中，奥美拉唑阻断了马槟榔刺激的eotaxin-3 mRNA和蛋白表达的增加。当受到Th 2细胞因子刺激时，GORD和EoE患者的食管鳞状细胞表达相似水平的嗜酸性粒细胞趋化因子-3，奥美拉唑阻断该嗜酸性粒细胞趋化因子-3的表达。这些结果表明，PPI可能具有独立于对酸反流的影响的嗜酸性粒细胞减少作用，并且对PPI的反应可能无法区分EoE和GORD。
Eosinophilic oesophagitis (EoE) and gastrooesophageal 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. Our objective 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. Using telomerase-immortalised and primary cultures of oesophageal squamous cells from GORD and EoE patients, we measured eotaxin-3 protein secretion stimulated by Th2 cytokines (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. 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. 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.
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