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评估白细胞介素 27 对慢性淋巴细胞白血病患者 B 细胞抗肿瘤作用的机制。

Evaluating the mechanism underlying antitumor effect of interleukin 27 on B cells of chronic lymphocytic leukemia patients.

机构信息

Faculty of Medicine, Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.

Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.

出版信息

J Cell Physiol. 2020 Dec;235(12):9424-9431. doi: 10.1002/jcp.29747. Epub 2020 May 7.

Abstract

Chronic lymphocyte leukemia (CLL) is a B-cell malignancy resisted to apoptosis. Recently, some studies indicated that cytokines such as interleukin 27 (IL-27) can reduce B-cell proliferation. The aim of this study is to evaluate the mechanism underlying the proapoptotic effect of IL-27 on B cells of patients with CLL in comparison with B cells of normal subjects. The effect of IL-27 on the antitumor activity of natural killer (NK) and T cells was also evaluated. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with CLL and 15 normal subjects. B cells and PBMCs were cocultured with IL-27 and B cells apoptosis to evaluate proliferation. Both messenger RNA and protein expression of IL-27 and IL-27 receptor were determined using flow cytometry and real-time polymerase chain reaction analysis. To evaluate the apoptotic effect of IL-27 on B cells of patients with CLL, Annexin V-FITC and 7-AAD (BioLegend) fluorescent dyes were used. In addition, the IL-27 effect on activation of T cell and NK cell was determined by determining CD96 molecule expression. IL-27 and IL-27 receptor expression in patients with CLL was significantly lower than that of normal subjects (p < .05). IL-27 enhanced apoptosis of B cells in patients with CLL (p < .05) but this effect was not significantly observed in B cells of normal subjects (p > .05). Consequently, IL-27 reduced the proliferation of B cells and enhanced NK cell activity (p < .05). IL-27, through inducing apoptosis, can exert an inhibitory effect on cancer B cells of CLL patients with minimal effect on normal B cells.

摘要

慢性淋巴细胞白血病(CLL)是一种抵抗细胞凋亡的 B 细胞恶性肿瘤。最近的一些研究表明,细胞因子如白细胞介素 27(IL-27)可以减少 B 细胞的增殖。本研究旨在评估与正常对照相比,IL-27 对 CLL 患者 B 细胞促凋亡作用的机制。还评估了 IL-27 对自然杀伤(NK)和 T 细胞抗肿瘤活性的影响。从 35 例 CLL 患者和 15 例正常对照中分离外周血单个核细胞(PBMC)。将 B 细胞和 PBMC 与 IL-27 共培养,评估增殖情况。通过流式细胞术和实时聚合酶链反应分析检测 IL-27 和 IL-27 受体的信使 RNA 和蛋白表达。为了评估 IL-27 对 CLL 患者 B 细胞的凋亡作用,使用 Annexin V-FITC 和 7-AAD(BioLegend)荧光染料。此外,通过测定 CD96 分子表达来确定 IL-27 对 T 细胞和 NK 细胞激活的影响。CLL 患者的 IL-27 和 IL-27 受体表达明显低于正常对照(p < 0.05)。IL-27 增强了 CLL 患者 B 细胞的凋亡(p < 0.05),但在正常对照的 B 细胞中未观察到明显的作用(p > 0.05)。因此,IL-27 降低了 B 细胞的增殖并增强了 NK 细胞的活性(p < 0.05)。IL-27 通过诱导细胞凋亡,对 CLL 患者的癌症 B 细胞发挥抑制作用,对正常 B 细胞的作用最小。

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