血管活性肠肽受体 CRTH2 拮抗剂治疗可改善嗜酸性粒细胞性食管炎中的嗜酸性粒细胞和肥大细胞介导的食管重塑和运动功能障碍。

Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.

机构信息

Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorder Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA.

Division of Gastroenterology, Cincinnati Childrens Medical Center, Cincinnati, OH 45229, USA.

出版信息

Cells. 2024 Feb 6;13(4):295. doi: 10.3390/cells13040295.

DOI:10.3390/cells13040295

PMID:38391908

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10886969/

Abstract

BACKGROUND AND AIMS

Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs.

METHODS

Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors.

RESULTS

In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. -PCR analysis revealed five- to sixfold increases in expression levels of , , and receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA levels and eosinophil- and nerve cell-derived s in human EoE ( < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE.

CONCLUSIONS

CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

摘要

背景与目的

超声检查显示，嗜酸性粒细胞在人类 EoE 的食管黏膜各节段积聚，最终导致食管运动功能障碍；然而，目前尚无机制证据解释这种积聚是如何或为何发生的。

方法

使用针对相关抗原和受体的特异性抗体进行定量 PCR、ELISA、流式细胞术、免疫染色和免疫荧光分析。

结果

在 EoE 患者的深部食管活检中，嗜酸性粒细胞和肥大细胞在每个食管节段与神经细胞衍生的 VIP 相邻积聚。PCR 分析显示，在人血液和组织中积聚的嗜酸性粒细胞和肥大细胞中，受体和蛋白的表达水平增加了五到六倍。我们还观察到人类 EoE 中 mRNA 水平与嗜酸性粒细胞和神经细胞衍生的 VIP 之间存在显著相关性（<0.05）。我们提供的证据表明，CRTH2 拮抗剂治疗后嗜酸性粒细胞和肥大细胞缺失可改善慢性 DOX 诱导的 CC10-IL-13 小鼠实验性 EoE 中的运动功能障碍。