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间充质基质细胞调节实验性结肠炎中的肠道炎症。

Mesenchymal stromal cells modulate gut inflammation in experimental colitis.

机构信息

Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo, São Paulo, Brazil.

Department of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil.

出版信息

Inflammopharmacology. 2018 Feb;26(1):251-260. doi: 10.1007/s10787-017-0404-6. Epub 2017 Oct 23.

Abstract

Inflammatory bowel diseases (IBDs) affect millions of people worldwide and their frequencies in developed countries have increased since the twentieth century. In this context, there is an intensive search for therapies that modulate inflammation and provide tissue regeneration in IBDs. Recently, the immunomodulatory activity of adipose tissue-derived mesenchymal stromal cells (ADMSCs) has been demonstrated to play an important role on several immune cells in different conditions of inflammatory and autoimmune diseases. In this study, we explored the immunomodulatory potential of ADMSC in a classical model of DSS-induced colitis. First, we found that treatment of mice with ADMSC ameliorated the severity of DSS-induced colitis, reducing colitis pathological score and preventing colon shortening. Moreover, a prominent reduction of pro-inflammatory cytokines levels (i.e., IFN-γ, TNF-α, IL-6 and MCP-1) was observed in the colon of animals treated with ADMSC. We also observed a significant reduction in the frequencies of macrophages (F4/80CD11b) and dendritic cells (CD11cCD103) in the intestinal lamina propria of ADMSC-treated mice. Finally, we detected the up-regulation of immunoregulatory-associated molecules in intestine of mice treated with ADMSCs (i.e., elevated arginase-1 and IL-10). Thus, this present study demonstrated that ADMSC modulates the overall gut inflammation (cell activation and recruitment) in experimental colitis, providing support to the further development of new strategies in the treatment of intestinal diseases.

摘要

炎症性肠病(IBD)影响着全球数百万人,自 20 世纪以来,发达国家的发病率有所增加。在这种情况下,人们正在积极寻找能够调节炎症并为 IBD 提供组织再生的治疗方法。最近,脂肪组织来源的间充质基质细胞(ADMSC)的免疫调节活性已被证明在不同的炎症和自身免疫性疾病条件下对多种免疫细胞具有重要作用。在这项研究中,我们探索了 ADMSC 在 DSS 诱导的结肠炎经典模型中的免疫调节潜力。首先,我们发现 ADMSC 治疗可改善 DSS 诱导的结肠炎的严重程度,降低结肠炎病理评分并防止结肠缩短。此外,在 ADMSC 治疗的动物的结肠中观察到促炎细胞因子水平(即 IFN-γ、TNF-α、IL-6 和 MCP-1)的显著降低。我们还观察到 ADMSC 治疗小鼠肠道固有层中巨噬细胞(F4/80CD11b)和树突状细胞(CD11cCD103)的频率显著降低。最后,我们检测到 ADMSCs 处理的小鼠肠道中免疫调节相关分子的上调(即精氨酸酶-1 和 IL-10 的表达增加)。因此,本研究表明 ADMSC 调节实验性结肠炎中的整体肠道炎症(细胞激活和募集),为治疗肠道疾病的新策略的进一步发展提供了支持。

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