Soluble Mediators Released from PI-IBS Patients' Colon Induced Alteration of Mast Cell: Involvement of Reactive Oxygen Species
Soluble Mediators Released from PI-IBS Patients' Colon Induced Alteration of Mast Cell: Involvement of Reactive Oxygen Species
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DOI：
10.1007/s10620-011-1897-2
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发表时间：
2012-02-01
影响因子：
3.1
通讯作者：
Guo, Chenghao
中科院分区：
文献类型：
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作者：
Han, Wei;Lu, Xuefeng;Guo, Chenghao
越来越多的证据表明，感染后肠易激综合征（PI-IBS）患者的肥大细胞活化增加，粘膜可溶性介质参与内脏痛觉过敏的病理生理学。此外，已有研究表明活性氧（reactive oxygen species，ROS）和蛋白酶激活受体（protease-activated receptors，PARs）是持续性痛觉过敏的介质，本文旨在探讨：（1）结肠组织可溶性因子对体外活化腹膜肥大细胞（peritoneal mast cells，PMC）的作用，（2）可溶性介质诱导PMC脱颗粒的作用是否与PARs的激活有关，以及PARs的激活是否与PMCs的激活有关。（3）活性氧清除剂苯基N-叔丁基硝酮（PBN）对上述改变的影响。评价PMC的活化。采用RT-PCR和免疫荧光双标法检测PMCs中PAR（2）的表达。给予PBN（10 mM）处理，然后再次观察先前的改变。PI-IBS诱导的PMCs中PAR（2）mRNA的表达较正常对照组明显增加。经PBN处理后，SUP对PMCs活性的增强作用减弱，PAR（2）mRNA表达明显降低。PMCs中PAR（2）的免疫反应也有类似的结果，表明ROS清除剂可逆转PI-IBS引起的PMCs活性增强，这种作用可能与PAR（2）的激活有关。这些发现可能为PI-IBS的新治疗靶点铺平道路。
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.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.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.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.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.