Oncostatin M Induces a Pro-inflammatory Phenotype in Intestinal Subepithelial Myofibroblasts.

IF 4.5 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Inflammatory Bowel Diseases Pub Date : 2024-11-04 DOI:10.1093/ibd/izae098

Georgios Kokkotis, Eirini Filidou, Gesthimani Tarapatzi, Michail Spathakis, Leonidas Kandilogiannakis, Nikolas Dovrolis, Konstantinos Arvanitidis, Ioannis Drygiannakis, Vassilis Valatas, Stergios Vradelis, Vangelis G Manolopoulos, Vasilis Paspaliaris, George Kolios, Giorgos Bamias

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引用次数: 0

Abstract

Background: Oncostatin-M (OSM) is associated with antitumor necrosis factor (anti-TNF)-α resistance in inflammatory bowel disease (IBD) and fibrosis in inflammatory diseases. We studied the expression of OSM and its receptors (OSMR, gp130) on intestinal subepithelial myofibroblasts (SEMFs) and the effect of OSM stimulation on SEMFs.

Methods: The mRNA and protein expression of OSM, OSMR, gp130, and several fibrotic and chemotactic factors were studied in mucosal biopsies and isolated human intestinal SEMFs of patients with IBD and healthy controls (HCs) and in a model of human intestinal organoids (HIOs). Subepithelial myofibroblasts and HIOs were stimulated with OSM and interleukin (IL)-1α/TNF-α. RNAseq data of mucosal biopsies were also analyzed.

Results: Oncostatin-M receptors and gp130 were overexpressed in mucosal biopsies of patients with IBD (P < .05), especially in inflamed segments (P < .05). The expression of OSM, OSMR, and gp130 in SEMFs from HCs was increased after stimulation with IL-1α/TNF-α (P < .001; P < .01; P < .01). The expression of CCL2, CXCL9, CXCL10, and CXCL11 was increased in SEMFs from patients with IBD and HCs after stimulation with OSM in a dose-dependent manner (P < .001; P < .05; P < .001; P < .001) and was further increased after prestimulation with IL-1α/TNF-α (P < .01 vs OSM-alone). Similar results were yielded after stimulation of HIOs (P < .01). Oncostatin-M did not induce the expression of collagen I, III, and fibronectin. Oncostatin-M receptor expression was positively correlated with CCL2, CXCL9, CXCL10, and CXCL11 expression in mucosal biopsies (P < .001; P < .001; P = .045; P = .033).

Conclusions: Human SEMFs overexpress OSMR in an inflammatory microenvironment. Oncostatin-M may promote inflammation in IBD via its stimulatory effects on SEMFs, which primarily involve chemoattraction of immune cells to the intestinal mucosa.

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肿瘤抑制素 M 诱导肠上皮下肌成纤维细胞的促炎表型

背景：Oncostatin-M（OSM）与炎症性肠病（IBD）的抗肿瘤坏死因子（anti-TNF）-α抵抗和炎症性疾病的纤维化有关。我们研究了OSM及其受体（OSMR、gp130）在肠上皮下肌成纤维细胞（SEMFs）上的表达以及OSM刺激对SEMFs的影响：方法：在IBD患者和健康对照组（HCs）的黏膜活检组织和分离的人肠SEMFs中，以及在人肠器质体（HIOs）模型中，研究了OSM、OSMR、gp130以及多种纤维化和趋化因子的mRNA和蛋白表达。用OSM和白细胞介素（IL）-1α/TNF-α刺激上皮下肌成纤维细胞和HIOs。同时还分析了粘膜活检组织的 RNAseq 数据：结果：IBD患者黏膜活检组织中的Oncostatin-M受体和gp130过表达（P 结论：IBD患者黏膜活检组织中的Oncostatin-M受体和gp130过表达：人类SEMFs在炎症微环境中过表达OSMR。Oncostatin-M可能通过其对SEMFs的刺激作用促进IBD的炎症，这主要涉及免疫细胞对肠粘膜的趋化吸引。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammatory Bowel Diseases 医学-胃肠肝病学

CiteScore

9.70

自引率

6.10%

发文量

462

审稿时长

1 months

期刊介绍： Inflammatory Bowel Diseases® supports the mission of the Crohn''s & Colitis Foundation by bringing the most impactful and cutting edge clinical topics and research findings related to inflammatory bowel diseases to clinicians and researchers working in IBD and related fields. The Journal is committed to publishing on innovative topics that influence the future of clinical care, treatment, and research.