间充质干细胞（MSCs）已被研究作为炎症性肠病（IBD）的治疗药物。刺激MSCs与促炎性细胞因子可以增强其免疫调节效应。然而，进一步研究仍有待支持MSCs在免疫介导性疾病和伴侣动物中的应用。该研究旨在评估肿瘤坏死因子（TNF）-α刺激下的猫脂肪组织源性MSCs（fAT-MSCs）在右旋糖苷硫酸钠（DSS）诱导的结肠炎小鼠模型中的治疗效果。小鼠通过饮用含3％ DSS的水制作结肠炎，fAT-MSCs经腹腔注射。结肠在第10天被收集。评估并比较疾病的严重程度。原始264.7细胞与培养基进行培养以确定机制，使用定量实时聚合酶链反应和酶联免疫吸附法。TNF-α刺激的fAT-MSCs在疾病活性、结肠长度、组织学评分和炎症性细胞因子方面更大程度改善了DSS诱导的结肠炎的严重程度。在切片的结肠组织中，与其他组相比，包括TNF-α刺激的fAT-MSCs的组具有较高比例的CD11b + CD206 +巨噬细胞。在体外实验中，TNF-α刺激增加了fAT-MSCs中环氧合酶-2（COX-2）表达和前列腺素E2（PGE2）分泌。来自TNF-α刺激的fAT-MSCs的培养基增强了LPS活化的原始264.7细胞中白介素-10和精氨酸酶-1的表达。这些结果表明，TNF-α刺激的脂肪MSC对炎症肠比起其他方式更有效地改善。此外，我们证明了这种效果与COX-2 / PGE2通路相关。©2023韩国兽医科学学会。

Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals.This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model.Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b+CD206+ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells.These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE2 pathway.© 2023 The Korean Society of Veterinary Science.