Soluble mediators released from PI-IBS patients' colon induced alteration of mast cell: involvement of reactive oxygen species.

BACKGROUND

Growing evidence suggests that patients with post-infectious irritable bowel syndrome (PI-IBS) have increased mast cell activation, and that mucosal soluble mediators are involved in the pathophysiology of visceral hyperalgesia. In addition, previous findings show that reactive oxygen species (ROS) and protease-activated receptors (PARs) are mediators of persistent hyperalgesia.

AIMS

This article aims to investigate: (1) the ability of soluble factors from colonic biopsies to active peritoneal mast cells (PMCs) in vitro; (2) whether the effects of PMCs degranulation induced by soluble mediators are related to PARs activation; and (3) the ability of phenyl N-tert-butylnitrone (PBN), a ROS scavenger, to modify these alterations.

METHODS

Supernatant (SUP) from colonic biopsies was collected and applied to PMCs for 12 h. Activation of PMCs was evaluated. The expression of PAR(2) in PMCs was examined by RT-PCR and double-immunofluorescence staining. PBN (10 mM) treatment was administered, then previous alterations were observed again.

RESULTS

Stimulation with SUP of PI-IBS led to an increase in activation of PMCs. PAR(2)mRNA expression was significantly increased in PMCs induced by SUP of PI-IBS compared to healthy subjects. After being treated by PBN, the SUP-induced enhancement of PMCs activities could be weakened, and PAR(2)mRNA expression was significantly decreased. A similar result of immunoreactivity for PAR(2) was observed in PMCs.

CONCLUSIONS

The study shows that ROS scavenger reverses the SUP of PI-IBS-induced enhancement of PMCs activities, and that these effects may be related to activation of PAR(2). These findings might pave the way to new therapeutic targets in PI-IBS.