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

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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.

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Acknowledgments

The study was granted and supported by the National Natural Science Foundation of China (No. 81200274, No. 81670487).

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Authors and Affiliations

  1. Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China

    Lijun Du, Yanqin Long, John J. Kim, Binrui Chen, Yubin Zhu & Ning Dai

  2. Division of Gastroenterology & Hepatology, Loma Linda University Health, Loma Linda, CA, 92354, USA

    John J. Kim

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  1. Lijun Du
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  2. Yanqin Long
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Contributions

ND and YQL designed the research; LJD, YBZ, and BRC performed the research; LJD analyzed the data; LJD, YQL, and JJK wrote the paper; and YQL and JJK revised the paper. All authors approved the final manuscript.

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Correspondence to Yanqin Long.

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Du, L., Long, Y., Kim, J.J. et al. Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice. Dig Dis Sci 64, 729–739 (2019). https://doi.org/10.1007/s10620-018-5367-y

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