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

  • Lijun Du
  • Yanqin LongEmail author
  • John J. Kim
  • Binrui Chen
  • Yubin Zhu
  • Ning Dai
Original Article



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


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


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.


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.


PAR-2 activation increases intestinal permeability leading to immune activation and visceral hypersensitivity in PI-IBS mouse model.


Protease activated receptor-2 Post-infectious irritable bowel syndrome Intestinal permeability Tight junction T helper 



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

Author’s contribution

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.

Compliance with ethical standards

Conflict of interest

No competing interests to declare.

Supplementary material

10620_2018_5367_MOESM1_ESM.docx (1.2 mb)
Supplementary material 1 (DOCX 1226 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Gastroenterology, School of Medicine, Sir Run Run Shaw HospitalZhejiang UniversityHangzhouChina
  2. 2.Division of Gastroenterology & HepatologyLoma Linda University HealthLoma LindaUSA

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