Protease activated receptor 4 status of mast cells in post infectious irritable bowel syndrome
Protease activated receptor 4 status of mast cells in post infectious irritable bowel syndrome
复制标题
感染后肠易激综合征中肥大细胞的蛋白酶激活受体4状态
DOI：
10.1111/j.1365-2982.2011.01841.x
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发表时间：
2012-02-01
影响因子：
3.5
通讯作者：
Guo, C.
中科院分区：
文献类型：
--
作者：
Han, W.;Wang, Z.;Guo, C.
研究背景越来越多的证据表明蛋白酶激活受体（PARs）是持续性神经病理性疼痛的介质，但其在感染后肠易激综合征（PI-IBS）患者中的可能作用尚待进一步探讨。本文旨在研究PAR 2和PAR 4在PI‐IBS患者结肠黏膜中的表达，重点关注与肥大细胞活化状态的相关性。MethodsA共有17名正常对照和23名PI‐IBS患者自愿参加本研究。采用RT-PCR和免疫组化方法检测PAR 2和PAR 4的表达和定位，采用免疫荧光双标法检测肥大细胞中PAR 2和PAR 4的表达。Key ResultsThe免疫组化研究显示，肥大细胞的上皮细胞和粘膜下细胞均呈PAR 2和PAR 4的免疫反应性。与对照组相比，PI‐IBS中蛋白酶激活受体4 mRNA表达和免疫反应性下调。具体而言，与正常对照组相比，在PI-IBS的肥大细胞中观察到PAR 4的免疫反应性降低，而PI-IBS和对照组之间的PAR 2无显著差异。PI‐IBS患者肥大细胞PAR 4免疫反应性降低，而肥大细胞活性升高，PI ‐IBS患者肥大细胞PAR 4免疫反应性降低。这可能是相当大的兴趣，了解持续性结肠超敏反应的机制及其作为PI-IBS治疗靶点的潜在作用。
BackgroundGrowing 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 PAR2and PAR4in the colonic mucosa of patients with PI‐IBS, focusing on correlation with mast cell activation status.MethodsA total of 17 normal controls and 23 patients with PI‐IBS volunteered the study. The expression and localization of PAR2and PAR4were investigated by RT‐PCR and immunohistochemistry, and the expression of PAR2and PAR4in the mast cells was examined using double‐immunofluorescence staining.Key ResultsThe immunohistochemical study revealed that epithelial and submucosal cells showed immunoreactivity for both PAR2and PAR4. Protease activated receptor 4 mRNA expression and immunoreactivity were down‐regulated in PI‐IBS compared with the control group. Specifically, a reduced immunoreactivity for PAR4was observed in mast cells of PI‐IBS compared with normal controls, whereas there are no significant differences shown in PAR2between the PI‐IBS and the control group. It is also found that the PAR4immunoreactivity decreases, while the activity of mast cells increases in PI‐IBS rather than normal controls.Conclusions & InferencesThis study outlines the down‐regulation of PAR4in 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.