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骨髓间充质干细胞对金黄色葡萄球菌肠毒素 B(SEB)存在时 U937 细胞的影响。

Bone marrow - mesenchymal stem cells impact on the U937 cells in the presence of staphylococcal enterotoxin B (SEB).

机构信息

Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences, Arak, Iran.

出版信息

Clin Exp Pharmacol Physiol. 2018 Aug;45(8):849-858. doi: 10.1111/1440-1681.12945. Epub 2018 May 10.

Abstract

The growing resistance against conventional chemotherapy in acute myeloid leukemia (AML) is a noticeable clinical concern. Therefore, many researchers are looking for novel substances to overcome drug resistance in cancer. Staphylococcal enterotoxin B (SEB) is a superantigen (SAg) and a promising compound which has lethal effects on malignant cells. In this unprecedented study, SEB was used against U937 cells in a co-culture system in the presence of human bone marrow-mesenchymal stem cells (hBM-MSCs). The effects of hBM-MSCs on the proliferation and survival of U937 cell line with SEB was assessed using MTT assay and AnnexinV/PI flowcytometry, respectively. Moreover, the expression of IL-6, IL-10, TGF-β, and inhibitor of nuclear factor kappa-B kinase (IKKb) was evaluated by real-time PCR technique. The same experiments were also carried out using hBM-MSCs-conditioned medium (hBM-MSCs-CM). The results showed that SEB reduced the proliferation and survival of U937 cell line, but hBM-MSCs or hBM-MSCs-CM suppressed the effects of SEB. Furthermore, real-timePCR demonstrated that SEB could decrease the expression of IL-6, IL-10, and TGF-β in hBM-MSCs (P < .05), while the production of IKKb was increased in comparison with the control group. These findings help us to have a broader understanding ofthe usage of SEB in the treatment of haematological malignancies, especially if it is targeted against hBM-MSCs to disrupt their supportive effects on malignant cells.

摘要

在急性髓系白血病(AML)中,传统化疗的耐药性日益增强,这是一个值得关注的临床问题。因此,许多研究人员正在寻找新的物质来克服癌症的耐药性。葡萄球菌肠毒素 B(SEB)是一种超抗原(SAg),是一种有前途的化合物,对恶性细胞具有致命作用。在这项前所未有的研究中,SEB 在存在人骨髓间充质干细胞(hBM-MSCs)的共培养系统中被用于 U937 细胞。通过 MTT 测定法和 AnnexinV/PI 流式细胞术分别评估 hBM-MSCs 对 SEB 存在下 U937 细胞系增殖和存活的影响。此外,通过实时 PCR 技术评估了 IL-6、IL-10、TGF-β 和核因子 kappa-B 激酶抑制剂(IKKb)的表达。还使用 hBM-MSCs 条件培养基(hBM-MSCs-CM)进行了相同的实验。结果表明,SEB 降低了 U937 细胞系的增殖和存活,但 hBM-MSCs 或 hBM-MSCs-CM 抑制了 SEB 的作用。此外,实时 PCR 表明 SEB 可以降低 hBM-MSCs 中 IL-6、IL-10 和 TGF-β 的表达(P<.05),而与对照组相比,IKKb 的产生增加。这些发现有助于我们更广泛地了解 SEB 在治疗血液恶性肿瘤中的应用,特别是如果它针对 hBM-MSCs 以破坏其对恶性细胞的支持作用。

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