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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 3/2019

01-03-2019 | Original Article

Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice

Published in: Digestive Diseases and Sciences | Issue 3/2019

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Abstract

Background

The role of protease activated receptor-2 (PAR-2) in the pathogenesis of abdominal pain in irritable bowel syndrome (IBS) is not well defined.

Aims

To investigate the role of PAR-2-mediated visceral hypersensitivity in a post-infectious IBS (PI-IBS) mouse model.

Methods

T. spiralis-infected PI-IBS mouse model was used. Fecal serine protease activity and intestinal mast cells were evaluated. Intestinal permeability was assessed by urine lactulose/mannitol ratio, and colonic expressions of PAR-2 and tight junction (TJ) proteins were examined by Western blot. Intestinal immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was evaluated by abdominal withdrawal reflex in response to colorectal distention.

Results

Colonic PAR-2 expression as well as fecal serine protease activity and intestinal mast cell counts were elevated in PI-IBS compared to the control mice. Decreased colonic TJ proteins expression, increased lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and visceral hypersensitivity were observed in PI-IBS compared to the control mice. Administration of PAR-2 agonist in control mice demonstrated similar changes observed in PI-IBS mice, while PAR-2 antagonist normalized the increased intestinal permeability and reduced visceral hypersensitivity observed in PI-IBS mice.

Conclusions

PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model.
Appendix
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Metadata
Title
Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice
Publication date
01-03-2019
Published in
Digestive Diseases and Sciences / Issue 3/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5367-y

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