Protease activated receptor 4 status of mast cells in post infectious irritable bowel syndrome

Abstract

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. 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. 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. 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.