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克罗恩病患者肠道及肠系膜脂肪组织中的Toll样受体4、F4/80和促炎细胞因子

Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in intestinal and mesenteric fat tissue of Crohn's disease.

作者信息

Leal Raquel F, Milanski Marciane, Ayrizono Maria de Lourdes S, Coope Andressa, Rodrigues Viviane S, Portovedo Mariana, Oliveira Luiza M F, Fagundes João J, Coy Cláudio S R, Velloso Lício A

机构信息

Coloproctology Unit, Surgery Department, University of Campinas (UNICAMP), Medical School São Paulo, Brazil ; Laboratory of Cell Signaling, Internal Medicine Department University of Campinas (UNICAMP), Medical School São Paulo, Brazil.

出版信息

Int J Clin Exp Med. 2013;6(2):98-104. Epub 2013 Jan 26.

Abstract

INTRODUCTION

Crohn's disease (CD) is a chronic intestinal ailment with a multifactorial etiology, whose incidence has increased during the last three decades. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected nearby the affected intestinal area; however, there are few studies on this aspect.

AIM

To evaluate inflammatory activity in intestinal mucosa and mesenteric fat tissue of patients with CD and controls.

MATERIALS AND METHODS

Ten patients with ileocecal CD and 16 patients with non-inflammatory disease (control groups) were studied. The specimens were snap-frozen and the expression of TLR-4, F4/80, IL1-β and IL-6 were determined by immunoblot of protein extracts. TLR4 RNA level were measured using RT-PCR. The t Test was applied (p<0.05). The local ethical committee approved the study.

RESULTS

The intestinal mucosa of CD group had significantly higher protein levels of TLR-4, F4/80, IL-1β and IL-6 than the controls. The gene expression of TLR4 was lower in the intestinal mucosa of CD compared to the control group. Regard the mesenteric fat tissue, there was no statistical difference related to TLR-4, F4/80, IL-1β and IL-6 proteins expression.

CONCLUSIONS

These findings may result from an up-regulation of macrophage activation and intracellular pathways activated by bacterial antigens, which are more important in intestinal mucosa than fat tissue in CD patients. This may represent an anomalous regulation of innate immunity and could contribute to the production of proinflammatory mediators and disease development.

摘要

引言

克罗恩病(CD)是一种病因多因素的慢性肠道疾病,在过去三十年中其发病率有所上升。最近,有人提出肠系膜脂肪在CD病理生理学中发挥作用,因为在受影响的肠道区域附近检测到脂肪肥大;然而,关于这方面的研究很少。

目的

评估CD患者和对照组的肠黏膜及肠系膜脂肪组织中的炎症活性。

材料和方法

研究了10例回盲部CD患者和16例非炎症性疾病患者(对照组)。标本速冻后,通过蛋白质提取物的免疫印迹法测定TLR-4、F4/80、IL1-β和IL-6的表达。使用RT-PCR测量TLR4 RNA水平。应用t检验(p<0.05)。当地伦理委员会批准了该研究。

结果

CD组的肠黏膜中TLR-4、F4/80、IL-1β和IL-6的蛋白质水平显著高于对照组。与对照组相比,CD患者肠黏膜中TLR4的基因表达较低。关于肠系膜脂肪组织,TLR-4、F4/80、IL-1β和IL-6蛋白表达无统计学差异。

结论

这些发现可能是由于巨噬细胞活化和细菌抗原激活的细胞内途径上调所致,在CD患者中,这在肠黏膜中比在脂肪组织中更重要。这可能代表先天免疫的异常调节,并可能促进促炎介质的产生和疾病发展。

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