Faculty of Medicine, Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.
J Cell Physiol. 2020 Dec;235(12):9424-9431. doi: 10.1002/jcp.29747. Epub 2020 May 7.
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.
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。
