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

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Abstract

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 PAR2 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. PAR2mRNA 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 PAR2mRNA expression was significantly decreased. A similar result of immunoreactivity for PAR2 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 PAR2. These findings might pave the way to new therapeutic targets in PI-IBS.

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Abbreviations

ABTS:

2,2-Azinobis-(3-ethylenbenzothiozoline-6-sulfonicacid)

BGA:

Brain–gut axis

GI:

Gastrointestinal

HBSS:

Hank’s buffer saline solution

HS:

Healthy subjects

IBS:

Irritable bowel syndrome

MCs:

Mast cells

NO:

Nitric oxide

OD:

Optical density

PARs:

Protease-activated receptors

PBN:

Phenyl N-tert-butylnitrone

PI-IBS:

Post-infectious irritable bowel syndrome

PMCs:

Peritoneal mast cells

ROS:

Reactive oxygen species

SUP:

Supernatant

TAC:

Total antioxidant capacity assay

TEAC:

Trolox-equivalent antioxidant capacity

WDR:

Wide dynamic range

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Acknowledgments

The study was supported by grants of National Natural Science Foundation of China (No. 30700358). It was also supported by the Outstanding Youth scientist research Foundation of Shandong Province (No. 2007BS03044). The authors would like to acknowledge the following individuals for their contributions: Yanxia Yu, Zhe Wang and Xiaoqin Liu.

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Authors and Affiliations

  1. The Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China

    Wei Han, Xuefeng Lu, Xiaoqing Jia & Tao Zhou

  2. Department of Pathology, Shandong University School of Medicine, 44 Wenhua West Road, Jinan, Shandong Province, China

    Chenghao Guo

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  1. Wei Han
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Correspondence to Chenghao Guo.

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Han, W., Lu, X., Jia, X. et al. Soluble Mediators Released from PI-IBS Patients’ Colon Induced Alteration of Mast Cell: Involvement of Reactive Oxygen Species. Dig Dis Sci 57, 311–319 (2012). https://doi.org/10.1007/s10620-011-1897-2

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  • DOI: https://doi.org/10.1007/s10620-011-1897-2

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