干扰素γ处理的巨噬细胞通过WNT信号通路诱导上皮-间质转化：在克罗恩病中的相关性

IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn's Disease.

作者信息

Macias-Ceja Dulce C, Coll Sandra, Bauset Cristina, Seco-Cervera Marta, Gisbert-Ferrándiz Laura, Navarro Francisco, Cosin-Roger Jesus, Calatayud Sara, Barrachina María D, Ortiz-Masia Dolores

机构信息

CIBERehd (Centro de Investigaciones en Red Enfermedad Hepática y Digestiva), Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, 46010 Valencia, Spain.

FISABIO (Fundación para el Fomento de la Investigación Sanitaria y Biomédica), Hospital Dr. Peset, 46017 Valencia, Spain.

出版信息

Biomedicines. 2022 May 8;10(5):1093. doi: 10.3390/biomedicines10051093.

BACKGROUND

Fibrosis is a common complication of Crohn's disease (CD) in which macrophages play a central role. Epithelial-mesenchymal transition (EMT) and the WNT pathway have been associated with fibrosis. We aim to analyse the relevance of the tissue microenvironment in macrophage phenotype and the EMT process.

METHODS

Intestinal surgical resections are obtained from control and CD patients with stenotic or penetrating behaviour. Cytokine's expression, macrophage phenotype, EMT markers and WNT signalling pathway are determined by WB, RT-PCR, ELISA or Cytometry. U937 cells are treated with IFNγ, TNFα, IL1β, IL4 or IL10 and co-cultured with HT29 cells and, in some cases, are treated with XAV939 or . The expression of macrophage, EMT and WNT pathway markers in U937 or HT29 cells is analysed by WB or RT-PCR.

RESULTS

IFNγ, WNT6, CD16 and CD86 are increased in the intestinal tissue of CD patients. IFNγ-treated U937 activated the EMT process and WNT pathway in HT29 cells, and the EMT process is mediated by FZD4.

CONCLUSIONS

An IFNγ-rich microenvironment polarises macrophages, which induces EMT through the WNT pathway.

背景

纤维化是克罗恩病（CD）的常见并发症，其中巨噬细胞起核心作用。上皮-间质转化（EMT）和WNT信号通路与纤维化有关。我们旨在分析组织微环境在巨噬细胞表型和EMT过程中的相关性。

方法

从具有狭窄或穿透性病变行为的对照患者和CD患者获取肠道手术切除组织。通过蛋白质免疫印迹法（WB）、逆转录聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）或细胞计数法测定细胞因子表达、巨噬细胞表型、EMT标志物和WNT信号通路。用γ干扰素（IFNγ）、肿瘤坏死因子α（TNFα）、白细胞介素1β（IL1β）、白细胞介素4（IL4）或白细胞介素10（IL10）处理人组织细胞淋巴瘤细胞系U937，并与结肠癌细胞系HT29共培养，在某些情况下，用XAV939或[此处原文缺失内容]处理。通过WB或RT-PCR分析U937或HT29细胞中巨噬细胞、EMT和WNT信号通路标志物的表达。