Coope Andressa, Pascoal Lívia Bitencourt, da Silva Francesca Aparecida Ramos, Botezelli José Diego, Ayrizono Maria de Lourdes Setsuko, Milanski Marciane, Camargo Michel Gardere, Planell Núria, Portovedo Mariana, Dias Cilene Bicca, Fagundes João José, Leal Raquel Franco
IBD Research Laboratory, Surgery Department, University of Campinas (UNICAMP), Medical School, Campinas, SP, Brazil.
Laboratory of Metabolic Disorders, Faculty of Applied Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Int J Inflam. 2017;2017:7646859. doi: 10.1155/2017/7646859. Epub 2017 Apr 9.
Crohn's disease (CD) is a chronic inflammatory disorder, characterized by cytokine imbalance and transcription signaling pathways activation. In addition, the increase of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Therefore, we evaluated the transcription signaling pathways and cytokines expression in intestinal mucosa and MAT of active CD patients. Ten patients with ileocecal CD and eight with noninflammatory diseases were studied. The biopsies of intestinal mucosa and MAT were snap-frozen and protein expression was determined by immunoblotting. RNA levels were measured by qPCR. The pIkB/IkB ratio and TNF level were significantly higher in intestinal mucosa of CD when compared to controls. However, STAT1 expression was similar between intestinal mucosa of CD and controls. Considering the MAT, the pIkB/IkB ratio was significantly lower and the anti-inflammatory cytokine IL10 was significantly higher in CD when compared to controls. Finally, the protein content of pSTAT1 was higher in MAT of CD compared to controls. These findings reinforce the predominance of the proinflammatory NF-kB pathway in CD intestinal mucosa. For the first time, we showed the activation of STAT1 pathway in MAT of CD patients, which may help to understand the physiopathology of this immune mediated disease.
克罗恩病(CD)是一种慢性炎症性疾病,其特征在于细胞因子失衡和转录信号通路激活。此外,病变肠道区域附近的肠系膜脂肪组织(MAT)增加是CD的一个标志。因此,我们评估了活动期CD患者肠黏膜和MAT中的转录信号通路及细胞因子表达。研究了10例回盲部CD患者和8例非炎性疾病患者。将肠黏膜和MAT活检组织速冻,通过免疫印迹法测定蛋白表达。通过qPCR测量RNA水平。与对照组相比,CD患者肠黏膜中的pIkB/IkB比值和TNF水平显著更高。然而,CD患者肠黏膜与对照组之间的STAT1表达相似。就MAT而言,与对照组相比,CD患者的pIkB/IkB比值显著更低,抗炎细胞因子IL10显著更高。最后,与对照组相比,CD患者MAT中pSTAT1的蛋白含量更高。这些发现强化了促炎NF-κB通路在CD肠黏膜中的主导地位。我们首次展示了CD患者MAT中STAT1通路的激活,这可能有助于理解这种免疫介导疾病的病理生理学。