Protease Activated Receptor 4 Status of Mast Cells in Post Infectious Irritable Bowel Syndrome

Background: Growing evidence suggests that protease activated receptors (PARs) are mediators of persistent neuropathic pain, but their possible function as mediators in patients with post infectious irritable bowel syndrome (PI-IBS) remains to be further explored. This article aims to investigate the expression of PAR(2) and PAR(4) in the colonic mucosa of patients with PI-IBS, focusing on correlation with mast cell activation status.

Methods: A total of 17 normal controls and 23 patients with PI-IBS volunteered the study. The expression and localization of PAR(2) and PAR(4) were investigated by RT-PCR and immunohistochemistry, and the expression of PAR(2) and PAR(4) in the mast cells was examined using double-immunofluorescence staining.

Key Results: The immunohistochemical study revealed that epithelial and submucosal cells showed immunoreactivity for both PAR(2) and PAR(4). Protease activated receptor 4 mRNA expression and immunoreactivity were down-regulated in PI-IBS compared with the control group. Specifically, a reduced immunoreactivity for PAR(4) was observed in mast cells of PI-IBS compared with normal controls, whereas there are no significant differences shown in PAR(2) between the PI-IBS and the control group. It is also found that the PAR(4) immunoreactivity decreases, while the activity of mast cells increases in PI-IBS rather than normal controls.

Conclusions & Inferences: This study outlines the down-regulation of PAR(4) in the mast cells of PI-IBS. It could be of considerable interests in understanding the mechanisms involved in the persistent colonic hypersensitivity and their potential role as therapeutic targets for PI-IBS.