Protease Activated Receptor-2 Induces Immune Activation and Visceral Hypersensitivity in Post-infectious Irritable Bowel Syndrome Mice
- 78 Downloads
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.
KeywordsProtease 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).
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.
- 14.Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, DC: National Academies Press; 2011.Google Scholar
- 15.National Research Council Subcommittee on Laboratory Animal. Nutrient Requirements of Laboratory Animals. 4th ed Washington, DC: National Academies Press; 1995.Google Scholar
- 53.Hockley JRF, Taylor TS, Callejo G, et al. Single-cell RNAseq reveals seven classes of colonic sensory neuron. Gut. 2018;0:1–12.Google Scholar