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信号转导子和转录激活子 1(STAT-1)的激活及干扰素-γ和抗炎蛋白在溃疡性结肠炎和家族性腺瘤性息肉病患者的盆腔回肠袋中的差异表达。

Activation of signal transducer and activator of transcription-1 (STAT-1) and differential expression of interferon-gamma and anti-inflammatory proteins in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.

机构信息

Coloproctology Unit, Surgery Department, University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil.

出版信息

Clin Exp Immunol. 2010 Jun;160(3):380-5. doi: 10.1111/j.1365-2249.2009.04088.x. Epub 2010 Mar 16.

Abstract

Pouchitis after total rectocolectomy is the most common complication of ulcerative colitis (UC). The immunological mechanisms involved in the genesis of pouchitis are unclear. Therefore, we evaluated the inflammatory activity in normal ileal pouch mucosa by determining signal transducers and activators of transcription (STAT-1) activation and cytokine expression in patients operated for UC and familial adenomatous polyposis (FAP). Eighteen asymptomatic patients, who underwent total rectocolectomy and J pouch, were evaluated: nine with UC and nine with FAP. The activation of STAT-1 and cytokine expression were determined by immunoblot of total protein extracts from pouch mucosal biopsies. The absence of pouchitis was assessed by clinical, histological and endoscopic parameters, according to the Pouchitis Disease Activity Index. The patients were not receiving any medication. Analysis of variance (anova) and Tukey-Kramer's test were applied. The local ethical committee approved the study and informed consent was signed by all participants. STAT-1 activation was increased in UC when compared to FAP and controls (P < 0.05). Higher levels of interferon (IFN)-gamma expression were observed in UC patients when compared to the control group (P < 0.05), but were similar to FAP. In contrast, cytokine signalling (SOCS-3) and interleukin (IL)-10 expression were similar in all groups (P > 0.05). These findings could explain the higher susceptibility to this inflammatory complication in UC when compared to FAP. A tendency towards increased levels of IFN-gamma and STAT-1 in patients with UC, even without clinical and endoscopic evidence of pouchitis, was observed; studying inflammatory activity in asymptomatic ileal pouches may help understanding of the pathogenesis of pouchitis.

摘要

全直肠结肠切除术后的袋炎是溃疡性结肠炎(UC)最常见的并发症。涉及袋炎发病机制的免疫机制尚不清楚。因此,我们通过检测接受 UC 和家族性腺瘤性息肉病(FAP)手术患者的正常回肠袋黏膜中转录激活子和转录因子(STAT)-1 的激活和细胞因子表达来评估其炎症活动。评估了 18 例无症状接受全直肠结肠切除和 J 袋成形术的患者:9 例 UC,9 例 FAP。通过 pouch 黏膜活检的总蛋白提取物的免疫印迹测定 STAT-1 的激活和细胞因子表达。根据 pouchitis 疾病活动指数评估 pouchitis 的缺失。患者未接受任何药物治疗。应用方差分析(anova)和 Tukey-Kramer 检验。当地伦理委员会批准了该研究,并由所有参与者签署了知情同意书。与 FAP 和对照组相比,UC 患者的 STAT-1 激活增加(P < 0.05)。与对照组相比,UC 患者 IFN-γ表达水平更高(P < 0.05),但与 FAP 相似。相反,细胞因子信号(SOCS-3)和白细胞介素(IL)-10 的表达在所有组中相似(P > 0.05)。这些发现可以解释 UC 患者比 FAP 更容易发生这种炎症性并发症的原因。在 UC 患者中,即使没有 pouchitis 的临床和内镜证据,也观察到 IFN-γ和 STAT-1 水平升高的趋势;研究无症状回肠袋的炎症活动可能有助于理解 pouchitis 的发病机制。

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