1. Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.
- Author
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Yadavalli CS, Upparahalli Venkateshaiah S, Verma AK, Kathera C, Duncan PS, Vaezi M, Paul RJ, and Mishra A
- Subjects
- Humans, Animals, Mice, Eosinophils, Receptors, Vasoactive Intestinal Peptide, Mast Cells pathology, Interleukin-13, Vasoactive Intestinal Peptide, Eosinophilic Esophagitis drug therapy, Eosinophilic Esophagitis pathology, Enteritis, Eosinophilia, Gastritis
- 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. qRT -PCR analysis revealed five- to sixfold increases in expression levels of VIP , CRTH2 , and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIP s in human EoE ( p < 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.
- Published
- 2024
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