Soluble Mediators Released from PI-IBS Patients’ Colon Induced Alteration of Mast Cell: Involvement of Reactive Oxygen Species

• Published in: Digestive diseases and sciences 2012-02, Vol.57 (2), p.311-319
• Main Authors: Han, Wei, Lu, Xuefeng, Jia, Xiaoqing, Zhou, Tao, Guo, Chenghao
• Format: Article
• Language: English
• Subjects: Adult; Antioxidants - therapeutic use; Biochemistry; Cell Degranulation; Colon - metabolism; Gastroenteritis - complications; Gastroenterology; Hepatology; Humans; Hyperalgesia - physiopathology; Intestinal Mucosa - physiology; Irritable bowel syndrome; Irritable Bowel Syndrome - complications; Irritable Bowel Syndrome - microbiology; Irritable Bowel Syndrome - physiopathology; Mast Cells - metabolism; Mast Cells - physiology; Medicine; Medicine & Public Health; Oncology; Original Article; Peritoneum - cytology; Proteases; Reactive Oxygen Species - metabolism; Receptors, Proteinase-Activated - physiology; RNA; Transplant Surgery
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-011-1897-2

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.